Health safari project implemented at NDMC Schools

Bright field image of HeLa cells Anti-microbial peptides grown in normal from wasp venom culture media

Annual National Facility for Rice leaffolder Marine Cyanobacterial culture Report Repository 2011-2012

Protein Nano Betanodavirus assay medicine prototype kit

Droplet based digital microfluidic platform Annual Report 2011-2012

Department of Biotechnology Ministry of Science & Technology Government of India

CONTENTS

Chapter – 1 : Overview 1- 34

Chapter – 2 : Human Resource Development 35-48

Teaching 35 Training Programmes 38 Fellowships 39 DBT Scholarships and Awards 43 Rapid Grant for young Investigators Scheme 45 DBT-CREST Award 46 Biotechnology Entrepreneurship Student Teams 46 Biotech Popularization and Promotion 47

Chapter – 3 : Biotech Facilities, Technology platforms & Research Resources 49-60

Centres of Excellence 49 Programme Support 52 Long term R&D Projects 55 Biotech Facilities and Research Resources 55 BUILDER Scheme 57

Chapter – 4 : Research and Development 61-168

Agricultural Biotechnology 61 Biofertiliser Biotechnology 77 Biopesticides and Crop Management 79 Bioresource Development and Utilization 83 Plant Biotechnology 92 Medicinal and Aromatics Plants 101 Animal Biotechnology-Production 103 Animal Health 109 Aquaculture and Marine Biotechnology 112 Seribiotechnology 119 Basic Research in Modern Biology 112 Contents Annual Report : 2011-12

Medical Biotechnology 127 Stem Cell Research 134 Bioengineering 136 Human Genetics and Genome Analysis 140 Environmental Biotechnology 143 Nanoscience and Nanobiotechnology 151 RNAi Technology platforms 155 Energy Bioscience Programme 159

Chapter – 5 : Biotechnology Programmes for Societal Development 169-185

Programmes for SC and ST Population 169 Programmes for Rural Development 174 Programmes for Women 180

Chapter – 6 : Biotech Product & Process Development 187-208

Small Business Innovation Research Initiative 187 Biotechnology Industry Partnership Programme 191 Biotechnology Industry Research Assistance Council 194 Biotech Product and Process Development 195 Biotechnological Approaches for Food and Nutritional Security 198 Biosafety Issues 202 Patent Facilitation Cell 208

Chapter – 7 : Biotechnology Information System Network 209-219

Chapter – 8 : Biotechnology Parks and Incubators 221-223

Chapter – 9 : International Collaboration 225-244

Chapter – 10 : Autonomous Institutions 245-284

National Institute of Immunology 245 National Centre for Cell Science 246 National Brain Research Centre 249 Centre for DNA Fingerprinting and Diagnostics 251 National Institute of Plant Genome Research 258 Annual Report : 2011-12 Contents

Institute of Life Sciences 261 Institute of Bioresources and Sustainable Development 263 Rajiv Gandhi Centre for Biotechnology 265 Institute for Stem Cell Science and Regenerative Medicine 268 Translational Health Science and Technology Institute 270 National Institute of Biomedical Genomics 272 Regional Centre for Biotechnology 273 National Agri-Food Biotechnology Institute 275 National Institute of Animal Biotechnology 283 Bioclusters 283

Chapter – 11 : Public sector Undertakings 285-286

Chapter – 12 : International Centre for Genetic Engineering 287-291 and Biotechnology

Chapter – 13 : Promotion of Biotechnology in the North Eastern 293-298 States of India

Chapter – 14 : New Legislations & Regulations 299-300

Chapter – 15 : Administration and Finance 301-305

Annexures I – VII 307-330

Abbreviations 331-339

Chapter 1

OVERVIEW

Rs. 23 crore in 1986-87 to Rs.1426.92 crore Preamble in 2011-12. The department moved with the progress from its single institute, National The year 2011-12 has been very significant Institute of Immunology, New Delhi to 14 in the life of the Department of autonomous institutions covering the areas Biotechnology. This year the department was of plant, human sciences, industrial rated as one of the Toppers amongst the biotechnology, stem cell science and first three Ministries/Department, by the regenerative medicine, translational health Cabinet Secretariat in the Government’s science, biomedical genomics, agri-food Performance Review. The department has biotechnology and animal biotechnology. completed 25 years of its existence and is The department is also committed to celebrating the Silver Jubilee this year. It is provide nearly two-thirds of its budget to therefore a right occasion for reflection. Universities and non-DBT institutes.

The department has grown into a major India needs to increase quality Ph.Ds atleast national research and development agency by three folds. The generation of Ph.Ds and presently providing nearly two-thirds of the scientific publications from India are showing research and development support in the a major upward trend and high quality life science sector. The department’s initial publication are increasing in number. The emphasis was on creating an institutional biotechnology industry has consistently framework for biological science and maintained growth of approximately 28% biotechnology, human resources at Ph.D. and in the last decade and nearly 46 products Post Doctoral levels, creating and nurturing have been commercialized by the biotech scientific and technology leaders in the industry in the country. Our regulatory country. The performance of department system has matured in its quality and supported universities and academia transparency and so has the ability to manage institutions in this field have been par- intellectual property, technology transfer, excellence. The budgetary allocation of the entrepreneurship and academia-industry department has increased from around relationship.

1 Overview Annual Report : 2011-12

From a few simple generic schemes, we for establishing a science based totally now have a large and diverse portfolio of autonomous, biotechnology regulatory schemes to support people, institutions and authority; initiation of special programmes universities, to promote excellence, to initiate to create interdisciplinary life science centres and effectively manage R&D networks in universities with 50% of our R&D nationally and globally. While nurturing expenditure in the university system. New basic and interdisciplinary science, DBT has initiatives in system biology, plant genomics effectively intervened to make a difference and molecular breeding, human and animal to the health sector, agriculture sector and vaccines, prospecting of bioresource for in catalysing and supporting development drugs, stem cell research and regenerative and diffusion of affordable technologies. medicine, food fortification for nutritionally The DBT’s critical role in these sectors is deprived segments of the population; to sustain high-end science, technology affordable health technology in implant and innovation and industry-academia inter- devices using the biodesign approach are action, complementing the efforts of agencies other key elements. like ICAR and ICMR. A device to manage faecal incontinence has The department has implemented over 90% been developed by the Fellows of the first of the recommendations of the national batch of the Stanford-India Biodesign biotechnology development strategy, built Programme implemented by DBT at AIIMS excellence in basic and interdisciplinary and IIT Delhi in collaboration with Stanford science, and produced and nurtured human University, USA. resources for innovation. Highlights of this are: establishment of seven new institutes The goals set in the biotechnology strategy designed to do both basic science and of a globally connected nationally relevant affordable technology; three new bioscience biotechnology sector are on its way of being clusters in Faridabad, Mohali and Bangalore; fulfilled with a remarkable increase in our full operationalization of two highly global partnership with almost every major acclaimed schemes of SBIRI and BIPP/ biotechnology nation covering North America, BIRAC for supporting partnership. Europe, Scandinavia, Australia, Canada, Russia and Cuba. The global partnership has Other highlights include Public-Private been strategically done to use and leverage Partnership, with about a 120 such projects India’s cost arbitrage for giving affordable in operation today, the cabinet approval solutions to our people. The effect of these

2 Annual Report : 2011-12 Overview

developments was visible in the last year The department has signed an MOU with when Indian biotechnology industry recorded the partner institutions for creating “Bio- approximately 25% growth and crossed US Cluster Board”, a legal entity for its $4 billion despite global recession. management and to synergize their intellectual strength and facilities to create The public private partnership and the a seamless campus. New schemes in North- increased availability of quality human Eastern region were implemented for resources, the ready access to research students from North East region for RA resources and our sophistication in fellowship and Biotech Industrial Training managing technology transfer resulted in a Programme offering industrial training to major push towards product development. fresh B.Tech/M.Sc./M.Tech students in Some of this includes commercialization of biotechnology in industry for a period of 6 three new influenza vaccines, bivalent polio months. This program is being implemented vaccine and pentavalent vaccine, by the Biotech Consortium India Limited meningococcal–B vaccine, low cost (BCIL) New Delhi. Through a special diagnostic for several infectious diseases, programme DBT has supported more than such as TB, Dengue fever, celiac disease 50 NER Scientists with Overseas and biogeneric drugs. Major push has been Associateship for undertaking research given to devices through the national bio- training abroad. design alliance linking engineering and medicine to produce locally relevant devices The newly established institutes namely, for patents and technology transfer. InStem, THSTI, NIBMG, RCB, NABI and NIAB started functioning actively. These The resurgence of research in application of institutes are successfully generating new approaches in agriculture such as competitive extra mural research grants and molecular breeding and application of RNAi pursuing projects in area of their research. strategy and molecular sciences in clean The department has established a Biotech energy areas by the small and medium Science Cluster in the NCR region of Delhi companies is evident from the analysis of as an institutional model for cutting edge the recent approvals in our public private research aimed at utilizing the various partnership programme. Translational centres of excellence for developing new research has acquired a new status in the hubs. InStem is developing collaborating country with our efforts, while basic science programmes with other institutes utilizing continues to grow in scale and quality. the infrastructure and facilities available in

3 Overview Annual Report : 2011-12

the cluster. The department is in the process emphasis on faculty training, hands on of implementation of Shahid Jameel training and industrial exposure to Committee’s recommendations for undergraduate students. DBT JRF and RA supporting the projects under the programmes have increasingly become Competitive Grants Scheme and introduced popular with students, which is evident from e-ProMIS system for online submission and considerable increase in the number of monitoring of proposals effective from applicants. 1st September, 2011. Department of Biotechnology jointly with Human Resource Development Tamil Nadu State Council for Science & Technology is supporting student research Skilled manpower is a key component for projects to develop and utilize the talent the scientific and socio-economic development and potential of students and train them for of the country. For achieving this objective, solving specific scientific and technological the department is implementing an integrated problems relevant to society. Under this human resource development program in Scheme, financial support is provided to biotechnology comprising of postgraduate encourage the U.G. (Engineering) and teaching program, doctoral and post-doctoral PG students (Bio-engineering/Physics/ fellowship as well as specialized training Chemistry/Medicine/Agriculture/ program for UG and PG teachers and mid- Veterinary/Environment /Social Sciences) career scientists. The department is providing enrolled in colleges and universities to take industrial training to biotechnology students up useful minor research projects as well to develop skills required for biotech as dissertation work. In keeping with the industries in country. The department has advancement of global networks for the initiated a Star College Scheme for development of biotechnology and the improvement of hands on training for department’s priority toward capacity undergraduate science students by providing building in human resources, under the support for infrastructure development with renamed CREST- Award (Cutting-edge emphasis on faculty training pursuing Research Enhancement and Scientific projects of day to day relevance and Training Award) scheme, 59 candidates were industrial exposure to undergraduate selected for Specialized Training of Young students. Under the scheme ‘Star College’, 46 Scientists in Niche Areas of Biotechnology. selected colleges have been provided TWAS-DBT fellowships for Post Graduates support for infrastructure development with and Post Doctoral fellowship were awarded

4 Annual Report : 2011-12 Overview

and five of the awardees completed the promising in terms of protection of mice training successfully and obtained their PhD from TB infection. Studies undertaken at degree. The Visiting Scientist from Abroad NII, New Delhi, led to identification of some Programme has also been enhanced. hits to tackle bacterial, mycobacterial and The department with Association of malarial affliction, characterization of novel Biotechnology Led Enterprises (ABLE) has molecular mechanisms involved in successfully conducted Biotechnology biosynthesis of mycobacterial virulent lipids Entrepreneurship Student Teams (BEST) in M. tuberculosis has opened new avenues programme to encourage young doctoral for drug discovery. High-throughput allele students in developing biotechnology determination for molecular breeding was entrepreneurship and exposing them to developed at ICRISAT, Patancheru, Andhra issues in commercialization of bio-science. Pradesh. SNP genotyping platforms for Centres of Excellence and Biotech molecular breeding applications have been Facilities developed in chickpea and pigeon pea. Efforts have also been made to deploy The COE scheme provides provision for marker-assisted back-crossing and marker- long term support in specific areas to excel, assisted recurrent selection approaches for innovate and create high quality intellectual enhancing drought tolerance in chickpea and property. The department has made a molecular mapping of fusarium wilt and tremendous progress in establishing and sterility mosaic disease in pigeonpea. creating the research related infrastructural Computational and System Biology facilities in several universities/institutions. Research undertaken at the NCBS, Bangalore The major facilities created are next and IISc., Bangalore has led to creation of generation DNA sequencing, proteomics, database of aligned protein domain platform for agriculture & veterinary science, superfamilies. A computational pipeline, service facilities like C-CAMP, Bangalore, Pocket Annotate has been developed. A and facilities for educational, teaching and genome wise dsRNA screen for genes training purpose. In addition, animal involved in endocytosis using a new resource facility is expanded and the methodology for screening of perturbation availability of synchrotron beamline made has been completed. A BSL-3 Containment possible for the biological science Facility has been established at the community. It led to the identification of 25 University of Hyderabad campus which is novel Mtb-specific antigens, out of which 8 undergoing testing for certification. antigens were found to be extremely Immunomodulatory role of a novel protein-

5 Overview Annual Report : 2011-12

chorismate mutase essential for survival of universities and another one-third budget on M. tuberculosis has been elucidated. its autonomous institutions for pursuing research and excellence. A two-tier Programme Support has been given to the monitoring mechanism has been put in place identified institution / department to create to evaluate proposals and the constant and strengthen research capabilities at endeavour is to identify leads and take them university or institutional level for forward to processes or products. categorical research in different disciplines for joint research efforts and to focus on Agricultural Biotechnology common research problems and enhancing the core competence of the institution/ The department has spent about 16% of department in bioreactors and tissue its R&D budget for the agricultural engineering of liver and cartilage, biotechnology programme during the year. development of chitosan based scaffolds The projects supported under this area and silk nanofibres for bone and cartilage have shown good progress in plant tissue regeneration. The department has molecular biology, genomics, genetic made good progress in establishing and transformation, marker assisted breeding creating the research related infrastructural to target the important traits related to facilities in several universities/institutions. biotic and abiotic stresses, productivity The existing repositories and depositories and nutritional enhancement in crops. are being strengthened. Four agricultural products viz. Cotton, Corn, Mustard and Sorghum were Research and Development approved for field trials under RCGM. A network project on development and The department supports research evaluation of salt and drought tolerant programmes in basic and specialized fields transgenic rice was pursued aiming of biotechnology across a wide range of areas towards development of salt and drought and sectors to develop basic knowledge, tolerant “marker-free” rice. The study technologies, processes and products relevant suggested that the accumulation of high to health, environment, industry and trehalose provide drought stress tolerance agriculture. The department spends about to transgenic rice plants. In a collaborative two-third of its budget on R&D activities out project between DBT and IRRI, fifteen of which, one-third of funding goes on R&D Indian institutions, including ICAR project sponsored to various institutes/ Institutes, State Agricultural Universities

6 Annual Report : 2011-12 Overview

and Central Universities with National genes through Marker Aided Breeding Research Centre on Plant Biotechnology (MAB). (NRCPB), New Delhi are participating in a network mode with NRCPB as the lead Biofertilizers centre. The programme envisages improving at least 12 popular rice varieties The department supports programmes for grown in the rainfed agri-eco systems developing biofertilizers and technology through marker-assisted backcross packages for their mass production. The breeding for flood, drought and salt focus of plant protection research is on tolerance. developing environmentally safe and economically feasible alternatives to Molecular cloning and characterization of chemical pesticides, using bio-technological salinity and/or drought stress-induced approaches. The department also focused helicase from rice and its functional on conversion of industrial agricultural validation is being carried out at ICGEB, wastes into biomanure and manage the New Delhi. A network programme on organic waste resources using low capital physical mapping and sample sequencing input protocols without expensive of wheat chromosome 2A was continued. laboratories and sophisticated industrial Other new projects on development of instruments. With the departmental micronutrient enriched maize through supports various biofertilizers and molecular breeding, crop biofortification technology packages for mass production of groundnut and pigeonpea were also developed have already been transferred to undertaken. A screening facility for iron industry for commercial production and and zinc bioavailability has been these have contributed significantly to the established. The department launched a agriculture production. Recently, mycorrhiza major translational project on crop biofertilizer technology package has been improvement where molecular markers transferred to an industry for the already available in public domain for biofertilizers production and they are important agronomic traits in wheat, rice, marketing in India and abroad. Presently, soyabean, chickpea and maize have been the emphasis is on development of validated and are being introgressed in integrated nutrient management packages the high yielding cultivated varieties for plantation crops and development of suitable to specific agroclimatic zones and liquid biofertilizers and also on also at all India basis by pyramiding development of microbial consortia for the

7 Overview Annual Report : 2011-12

effective formulation of optimal strains of for the mass production technologies and plant growth promotion in rice and bio bio formulations of certain bio control control against rice fungal and bacterial agents. Projects were implemented on pathogens. Under an Indo-Swiss formulation of mycorrhiza and collaboration programme the bionoculants, agriculturally important microorganisms a combination of consortia AMF and two of (AIMs). A comprehensive website on bio- the Plant Growth Promoting Rhizobacteria pesticide has been developed for updation, (PGPR) resulted in enhancement of rice yield up gradation and maintenance of of by 26% and 30% with under field trials. web based knowledge resource on The technology developed is under way for biopesticides. The website updated with commercialization. The department has set information on more than 250 completed up a Centre of Excellence at AAU, Jorhat projects which benefits scientists, for biopestide production and strain entrepreneurs and farmers. improvement and new strains of bioinoculates isolated & identified and their Bioresources production technology being standardized. Programme is being pursued on Bio-pesticides bioprospecting, inventorization and characterization, value addition and A number of research projects have been sustainable utilization of bioresources along supported for the control of pests and with relevant training, capacity building and diseases of economically important crops, awareness generation. NBDB focuses thereby enhancing the agricultural programmes on the application of productivity for sustainable development. biotechnological and related scientific Metarhizium anisopliae conidia were found approaches for R&D and development of to be effective in controlling mealy bug in new products and processes sustainably grapes. Four sex pheromone components utilizing the rich biodiversity. The largest and three aggregation pheromone collections of nearly 250000 microbial components were successfully isolated and cultures were screened for four different identified from Caryedon serratus. Synthesis therapeutic targets. A total of 16123 three of certain pheromone components has been stars hits were obtained of which 518 achieved which successfully trapped C. showed anti-cancer, 3643 showed anti- serratus adults in laboratory cage inflammation, 6676 showed anti- diabetic and experiments. Patents have also been filed 5286 showed anti-infective activities. These

8 Annual Report : 2011-12 Overview

potent cultures selected in the above Insecticide Board has approved the exercise are being used to generate the list registration of “TERI-DBT Bollcure” for of 1000 cultures to be taken in the next commercialization across India. Bollcure is phase of the program for identification of environment friendly, suitable for both novel drug scaffolds. In a programme of organic and IPM crop practices. prospecting of genes and molecules for product development, projects were Plant Biotechnology supported for prospecting of novel genes, molecules, enzymes etc. from plants, The department supported programmes in microbes, fungi, lichens for production of the area of Plant Biotechnology on basic potential products of industrial importance. research, forestry, horticultural and plantation Novel genes/promoters, transcription factors crops, metabolomics etc. Nutritional and were identified so as to develop transgenics shelf life improvement programme were for biotic/abiotic stress and for undertaken to enhance nutrient levels such understanding different metabolic as of flavonoids, carotenoids and folate, using engineering pathway(s) operative in a induced mutations/ transgenic manipulations system. In a project on bio-prospecting of and enrichment of Total Soluble Solids (TSS) selected lichen and plant species for product in fruits for making tomato suitable for development against cancer and processing. Study is also being initiated on tuberculosis, MSSRF has isolated four novel genome analysis of SNP’s/mutations/ compounds from lichen species The novel transcriptome/proteome in cultivars and the compound isolated from mycobiont cultures wild accessions of tomato using whole showed significant antitubercular activity genome sequencing and reverse genetic tools against Multidrug resistant (Rifampicin and for improving desired traits. Transgenic isoniazid resistant M. tuberculosis strains), at tomato lines expressing polyamine genes a concentration on 0.1mg/ml. MSSRF has under fruit specific promoter for post-harvest established lichen cultures of Roccella quality developed have been tested for post montagnei, Dirinaria applanata, Parmotrema harvest quality traits. prasorediosum Ramalina pollinaria, Trypethelium eluteriae and Usnea complanata for the Two transgenic lines resistant to Tomato Leaf biosynthesis of novel and known secondary Curl Virus (ToLCV) using antisense replicase compounds. A biopesticide formulation gene have been developed and basic (Bollcure) developed from eucalyptus has information generated is being taken further been transferred to two industries. Central to develop tomato varieties with broad

9 Overview Annual Report : 2011-12

spectrum resistance to (ToLCV) and Tospo for conservation, isolation and virus by appropriate gene deployment characterization of novel bioactive agents, strategy through marker aided selection. development of herbal formulations, genomics and biosynthetic pathway studies. A network programme was initiated on Important medicinal plants of Manipur hills Metabolomics focusing on crops like tomato, such as Paris polyphylla, Curcuma angustifolia rice, potato, maize, Arnebia, Curcuma etc. to and Zingiber zerumbet have been collected develop complete metabolomics profile of and maintained in the germplasm bank at potato, understand metabolomics of tomato Krishi Vigyan Kendra – Sylvan, Senapati with reference to fruit quality, aroma, District, Manipur. A network project for nutritional quality, study changes in identification of high camptothecin yielding transcriptome, proteome and metabolite clones and development of agrotechnology profile in maize (as induced by Nitrogen sustainable harvesting methods in and Phosphorus stress), secondary metabolite Nothapodytes nimmoniana is continuing at pathway related to shikonin synthesis UAS, Bangalore, UAS, Dharwad (College of (Arnebia), metabolomics related to stress and Forestry, Sirsi) and Research and Action in disease resistance (rice) and assessment of Natural Wealth Administration, Pune. therapeutic properties in curcuma. Protocol has been standardized for extraction and estimation of camptothecin A new variety IIHRP1 was developed and from leaf tissues of N. nimmoniana. Over validated in farmers fields and it has been 5000 seedlings of N. nimmoniana were approved for release as ‘Arka Flame’ by introduced into various agro-forestry Karnataka State varietal release committee. systems and development of coppicing Around 73,000 certified disease free Nagpur technology to maximize camptothecin yield Mandarin bud grafts have been released to has been developed. Efforts were initiated growers/nursery owners in Maharashtra, to develop diagnostics for better M.P, Bihar, Orissa and Southern State and management of begamoviruses infecting method for production of disease free Mentha spp at CIMAP, Lucknow. In the work planting material. undertaken on genomics and biosynthetic pathways at University of Jammu, eleven Medicinal and Aromatic Plants genes involved in mucilage biosynthetic pathway identified in Isabgol (Plantago ovata), Biotechnological intervention on medicinal Jammu. Studies on designing and and aromatic plants (MAP) was continued preparation of microarray chip to analyze

10 Annual Report : 2011-12 Overview

the terpene pathway in aromatic plants are of protein and energy supplement in feed progressing at CIMAP, Lucknow. was studied. Suitable enzyme formulations and their encapsulation process were Animal Biotechnology developed for improving the feed efficiency in poultry and pig. A new Efforts were continued to improve the method of forced moulting in white leghorn productivity of livestock animals. To hens using Zinc and Chromium was enhance the reproductive efficiency of developed which can be effectively used at Mithun, techniques of artificial insemination, the commercial scale. preservation of semen and embryo transfer were standardized and calves were born. A “Translational Research Platform for Embryo transfer techniques and ovum pick Veterinary Biologicals” (TRPVB) has been up technique for harvesting Yak embryos established at Tamil Nadu Veterinary and were standardized. Transgenic mice model Animal Sciences University (TANUVAS), expressing enhanced green fluorescent Chennai in September 2011. This platform protein (EGFP) gene in its mammary gland would facilitate the translation of technologies was developed using construct with EGFP by performing product development, gene cloned under buffalo beta casein validation, obtaining regulatory approvals promoter and attempts are on to express facilitate product commercialization and also human proteins of therapeutic value in be a referral center to strengthen linkages the milk of buffalo. A knockout mice model and collaboration in the area of animal was also developed by deleting Wdr13 gene vaccine and diagnostics development, which plays an important role in obesity exchange of biological materials, technology and metabolism. Sperm specific antigens of assessment, supporting training, consultation dogs having immunocontraceptive potential and IP development. were isolated, identified and characterized. The reproductive efficiency of local sheep Aquaculture and Marine breed of Kashmir and Lonand strain of Biotechnology Deccani sheep was enhanced by introgressing fecundity B (FecB) gene and Projects were supported on aquaculture feed, high litter size of FecB carrier sheep was development of therapeutic feed, reported both at experimental and farmers identification of novel bioactive molecules, level. Utilization of nonconventional oil marine extremophiles, molecular cakes as an alternate to oil cakes as a source characterization, induced maturation in

11 Overview Annual Report : 2011-12

shrimp, production of male ornamental fish, with an industrial partner. A method for development of molecular markers for application of sericin to cotton knits to get disease resistance, diagnostics and vaccines, a value-added finished product is under in vitro model for viral replication and investigation with a local garment development of cell lines etc. An Indo- manufacturing company. BmNPV resistant Norway joint collaborative programme on strains of silkworm (Bombyx mori) have been fish vaccine development was implemented. developed using marker-assisted breeding Technologies were developed and patented jointly at Seribiotech Research Laboratory with the leads obtained along with a good (SBRL), Bangalore and Andhra Pradesh State number of publications in this programme. Sericulture Research and Development Initiatives were taken for formulating a multi Institute (APSSR&DI), Hindupur. Studies on centric programme on whole genome ethology and hybrid compatibility of various sequencing of commercially important ecoraces of tasar silkworm (Antheraea mylitta) freshwater fishes - Labeo rohita and Clarias have been initiated at Kakatiya University, batrachus. Another programme on marine Warangal. A Consortium on Mulberry actinobacteria was also formulated for Genomics (CPMG) involving four exploring novel and product development. institutions – CSRandTI, Mysore, CSGRC, Hosur, UAS, Bangalore and UDSC, New Seribiotechnology Delhi has been continued. Genomic SSR markers have been identified and mapping Programme continued on improvement of populations segregating for root traits and productivity, enhancement of silk quality, WUE established for construction of linkage host-plants interaction and post-harvest map in mulberry using the co-dominant SSR processing of silk along with utilization of markers. Silk based supermacroporous by-products in sericulture. A new initiative cryogel matrices have been synthesized by on application of silk protein was cryogelatin technology for exploring their undertaken as potential biomaterial. A potential in cell-material interactions at IIT, Consortium Programme on Mulberry Kanpur. Silk fibroin-agarose cyrogel Genomics has been initiated during the year. composites showed fast swelling kinetics, SNP discovery and trait specific high-water uptake and good flow rates. transcriptome analysis of Indian mulberry These have shown good cell attachment and has been taken up. A pilot plant for the proliferation properties during interaction recovery of sericin from the waste with fibroblasts. Efforts have been initiated degumming liquor of silk has been set up on utilization of commercial silk waste as

12 Annual Report : 2011-12 Overview

potential nano-biomaterial at RV College of and computational approach. It is Engineering, Bangalore. Process for anticipated that such an approach may extraction and preparation of nano sericin reveal new strategies for the treatment of material has been standardized. TB infection.

Basic Research in Modern Biology Medical Biotechnology

The department through basic research The department has progressively increased programme in Modern Biology has been the expenditure under the broad areas of supporting a number of research projects medical biotechnology and health related to increase the competency of basic aspects and spending around 30% of its research. Important leads obtained in R&D budget. The medical biotechnology many of the basic research studies led and health related aspects included have to strengthening of applied research infectious disease biology, chronic disease and better understanding of the basic biology, vaccine research & development principles. For the first time functional and human genetics & genomics. expression of full length channel rhodopsin in yeast expression system has been Infectious Disease biology reported at Delhi University. In another work, IISc has shown a single mammalian The department has promoted research and mitochondrial translation initiation factor development activities in the area of to functionally replace two bacterial infectious diseases specifically relevant to factors (IF1 and IF2). Studies at the country caused by various pathogenic Chittaranjan National Cancer Institute, agents including bacteria, viruses, parasites, Kolkata have revealed that dopamine can fungi and others. Programs were supported significantly inhibit lung tumor growth in- to develop preventive, therapeutic and vivo and in-vitro by targeting tumor blood diagnostic tools for infectious diseases such vessels. The department has initiated a as Tuberculosis, Cholera, HIV/AIDS, network program under Systems Biology Hepatitis, Influenza, Chikungunya, Malaria, with focus on resolving and understanding Leishmaniasis etc. A multiplex PCR based the regulatory dynamics of interaction detection kit has been developed, validated between Mtb and the cellular component and patented for the rapid detection of STDs of the host using a systems level approach caused by Neisseria gonorrhoea and Chlamydia and combining experimental, theoretical trachomatis.

13 Overview Annual Report : 2011-12

Early pregnancy associated protein-1 Chronic Disease Biology (Epap-1), isolated from the first trimester placental tissue, blood and urine of The department is emphasising on the pregnant women during first trimester has chronic disease area covering patho-biolgical been shown to inhibit HIV-1 entry and is aspects of various cancer, pathway found to have affinity to HIV-1 gp120. A discovery, drug-interventions, biomarkers rapid IgM ELISA assay as a diagnostic etc. The curcumin clinical trials in cancer tool for dengue infection has been have reached a critical stage. DBT had set- developed and validated. up a “Curcumin Clinical Pharmacology Lab” at ACTREC, Mumbai for pharmacological DBT-ICMR collaborative programme on assessment of curcumin and its metabolites “HIV/AIDS and Microbicides” was in serum/plasma of patients on curcumin implemented for basic and translational intervention. The first lot of analysis has research on immunopathogenesis of HIV been done. The trials on oral-pre-cancer and development of therapeutic strategies. lesions have been completed. The It has played an integral role in supporting department has funded a project to explore the transition of anti-viral candidates from the pathogenesis of idiopathic nephrotic early discovery to initial clinical testing. syndrome of childhood and leads from this The 2nd phase of the programme has been study are likely to provide evidence for announced aiming at accelerating research cytokine polarization of T-helper cells. On that will generate knowledge and develop the long-term, this study might contribute state-of-the-art technologies to provide the to discovery of a biomarker for the basis for the development of HIV vaccines Nephrotic Syndrome disease course. and novel therapies against HIV including microbicides. In order to neutralize diverse A project was pursued to determine the HIV isolates, E coli expressed Outer presence of autoantibodies against factor H Domain based immunogen (ODEC) has in Indian children with Hemolytic Uremic been shown to be highly immunogenic Syndrome and their relation to disease which resulted in neutralization of B and severity, course and to characterize the C subtypes. Similarly CD4Bs, a gp120 antibodies and devise better treatments for based fragment, was found to elicit better the future. The department has funded a neutralization than gp120. Attempts are project towards the development of a rapid, being made towards patenting the CD4Bs indigenous test for diagnosis of celiac immunogens. disease. An ELISA kit has been developed

14 Annual Report : 2011-12 Overview

under this project. The kit has been tested on neuronal and non-neuronal cells via a against well-characterized sera samples and combination of molecular biology and also on sera collected prospectively from proteomic approaches, elucidating the children diagnosed with celiac diseases. cellular entry mechanisms of JEV using high- resolution imaging based studies, An immuno-chromatographic, a rapid visual development of high throughput assay test named “Crystal TB confirm” was methods (in vitro and ex vivo) to screen for developed by scientists at University of novel anti-virals effective against JEV and Delhi South Campus (UDSC) for detection studying the role of micro RNAs in JEV of tubercle bacilli in culture. This test replication and pathogenesis. confirms NTM versus MTB and provides results in less than twenty minutes. The kit Stem Cell Research has been launched and is being manufactured by M/s Span Diagnostics Ltd, A number of programmes on various aspects Surat. of embryonic and induced pluripotent stem cells have been generated and implemented Vaccine Research and Development for research. Programmes have also been implemented for basic and clinical research In vaccine development phase III trial of an using adult stem cells and over 45 oral rotavirus vaccine 116E is being carrying institutions, hospitals and industry are out at VIDRC. The laboratory has GLP involved in stem cell research in the country. compliant QA/QC processes and fully An institute for Stem Cell Biology and validated equipment. The vaccine efficacy Regenerative Medicine (InStem) has been assays are internationally cross-validated established at Bangalore with its translational and technicians are very well trained. units at Christian Medical College, Vellore. Another activity relates to a research GMP and clean room facilities have been programme pursued towards developing established in various medical schools. The novel vaccine delivery vectors. The group centre at Vellore is dedicated for translational is also focusing on immunogenicity of JEV stem cell research in a medical environment envelope protein in mice delivered using established with several basic and clinical Ovine Adenovirus, development of chimeric (physician) scientists involved in stem cell Adenoviruses for targeted delivery of research. Initiatives have been taken to enable therapeutic molecules to brain, identification rapid expansion of cutting edge scientific of the JEV attachment and receptor system activities at InStem and new research group

15 Overview Annual Report : 2011-12

have been identified for collaborative science models, evaluation of alginate, chitin and chairs in the interdisciplinary areas to chitosan bandages based on hydrogels with generate a vibrant atmosphere of international non-toxic ZnO/Herb Hemigraphis alternata exchanges especially for young researchers nanoformulations for wound dressing to work on joint projects with their applications and development of a international collaborators. Three young microfluidic device to study the aggregation scientists are being trained on DBT overseas of the β–amyloid peptide in scheme in top laboratories in USA in specific neurodegenerative diseases. areas of application to be developed at the centre. Human Genetics and Genome analysis Bioengineering Major projects have been initiated involving A number of bioengineering projects have clinicians, molecular geneticists and been initiated to address the challenges anthropologists in human genetics and involved and provide new vistas required genome analysis. Genetic resources are being for understanding the intricacies involved utilized to develop baseline data on various in applied research. Some of the significant ethnic groups for disease susceptibility and approaches include investigation of provide genetic services to a large number biomechanical factors responsible for of families including prenatal diagnosis and loosening and eventual failure of an implant, counselling to affected families including developing a novel microscopic technique tribal population and awareness among based on photothermal detection of metallic public regarding prevalence of common nanoparticle labels, designing mechanistic genetic disorders in the country like model for predicting the growth of thalassemia, DMD, SCD, haemophilia etc. aneurysms in an arterial bifurcation and The department has focused on disease developing novel intelligent peptides for based human genome analysis program by targeting peptide nucleic acid into cell for setting up genetic clinics anticipating that an effective drug delivery vehicle. Other the HGP data will be available in public initiatives include development of a liver domain. A human DNA profiling Bill has assist device for the temporary treatment of been formulated by the department and is patients with acute and chronic liver failure, being further revised based on the 3-D cellular dermal matrices for discussion held with the experts to bring reconstructive surgery in laboratory animal more clarity on various issues.

16 Annual Report : 2011-12 Overview

opportunity that combines multidisciplinary Environmental Biotechnology approach and finds applications in a variety of areas including drug delivery system, Environmental biotechnology research and new therapeutics, imaging, multifunctional development programmes are focused on the intermediates in biomedical devices etc. DBT development and use of biotechnological promoted research activities in these areas. tools for management of environment and A process was developed for the delivery biodiversity conservation. The focus was on of active molecules to nucleus and brain. development of mitigation technologies for Novel stimuli responsive graft copolymeric climate change, microbial technologies for nanoparticles based on polymers like environmental improvement, treatment of chitosan and fibrinogen was synthesized as industrial effluent, bioremediation of a promising smart material for the controlled xenobiotic compounds and biodiversity cancer drug delivery applications. conservation and characterization. Studies on Multimodal contrast agent based on bio- microbial diversity of various environments mineral nanoparticles was developed with and their genetic information were carried image enhancing abilities for different out for isolating micro-organisms that could medical imaging modalities such as nuclear be used in the manufacture of enzymes and magnetic resonance, X-ray-CT and near a wide range of bioactive compounds, as infrared (NIR) fluorescence, and Raman well as in bioremediation processes. A pilot imaging, together with targeted drug or scale facility of bioreactor with working gene delivery properties. NaoZno film was volume of 1000 liter has been established by used as smart food packaging material with TERI at Gualpahari. A study was carried out antibacterial properties. Extensive research on utilization of biodiesel waste by on Nanotoxicolgy is being continued to Pseudomonas sp. for production of phenazine understand various physicochemical antibiotics. A protocol of biological parameters associated with toxicity of production of PCN comprising raw glycerol different nanomaterials. was developed and standardized using standard culture NCIM 2141. RNAi Technology Platforms Nanoscience and RNAi approaches are extensively being Nanobiotechnology used as tool in understanding various gene Nanobiotechnology is a rapidly growing silencing mechanisms. RNAi approach was area of scientific and technological used in management of diseases of

17 Overview Annual Report : 2011-12

important crop and conferring attributes to Advanced Bio-energy has been established the plant to combat other biotic and abiotic at R&D IOCL Faridabad. stresses. The department supported research projects on development and application of Biotechnology Progarmmes for RNAi approach in the management of Societal Development various diseases, pests, enhancing the shelf life of the fruits and vegetables and making Programmes for SC/ST and Rural plants to withstand biotic and abiotic Population stresses. Application of RNAi technology has proven as an excellent tool in the area The programmes were continued for the socio- of therapeutics. economic upliftment of SC/ST rural and women population. Diffusion of technological Energy Bioscience Programme know-how in proven and field tested interventions were disseminated on production Energy Bioscience has been identified as of quality planting material, bio-control agents, priority area. The department has taken a vermicomposting, organic pepper cultivation, lead role in developing a research base in lac cultivation, sericulture, activities relating our country in the area of Energy Bioscience. to animal husbandry like artificial DBT has established network of more than insemination, goat rearing, quail production, 50 universities, research institutes and rabbitry etc to the target beneficiaries. In industry in close partnership, which are addition various programmes were working to realize the goals set in national undertaken on aspects of health awareness, biofuel mission. Among various bio-fuels, value addition and development of products bioethanol and biodiesel are being focused like soya milk, flour etc. Demonstrations and for scale up whereas others like bio-butanol trainings activities benefited a large number and bio-hydrogen are still at R&D stages in of SC/ST and rural people. The department India. Efforts are continuing for feedstock also supported eight bio-events to exhibit rural development, biomass production and products and processes for promotion and optimization of production technologies for marketing at the rural level and creating scale-up to make them commercially viable. awareness among the target community to The DBT–ICT Centre for biosciences is take up such activities for supplementation giving focus on developing biotechnologies of their income. The division is promoting for deriving energy from renewable new rural bio-entrepreneurship through resources. The DBT-IOCL Centre for establishment of rural bio resource complexes.

18 Annual Report : 2011-12 Overview

Programme for Women supports R&D, process and product development in industry. During the The Biotechnology based programme for present Plan Period, the SBIRI has made women is intended to benefit a large number a mark in the biotech sector. The efforts of women by improving their socio- of the department towards promotion of economic status through developing specific small and medium enterprises focusing skills among them through various on scientific innovations have been biotechnological interventions. The projects appreciated by the stakeholders. SBIRI supported under this programme cover has helped many small and medium training, field demonstrations, extension enterprises to establish proof-of-concept activities, enterprise development etc. in and to work on innovation R&D through areas such as horticulture, mushroom its Phase-I funding through which the cultivation, biofertilisers, biopesticides, industries were supported primarily in aquaculture, animal husbandry, poultry the form of grants-in-aid. The scheme farming, production of diverse value added also supported industries towards late marketable products. The department has stage R&D resulting into process and taken a major initiative during the year to product development through its Phase- address various R&D components on II funding. As in the earlier years, this women health care, nutrition and hygiene year also three Road-Shows were related aspects. The projects supported are conducted at Kolkata, Mumbai and being implemented at the community level Kochi. The participation of the private for the benefit of large number of women. sector was overwhelming. Such promotional activities and also Biotech Product and Process advertisement of the scheme in national Development dailies as well as in local newspapers has resulted in a continuous flow of INDUSTRY SCHEMES applications from industries. Under the scheme, the department has so far Small Business Innovation Research received more than 900 proposals and Initiative (SBIRI) has sanctioned 105 projects. Around 540 industries throughout the country have Small Business Innovation Research approached the department seeking Initiative (SBIRI) is the pioneering support under the scheme. Currently 52 programme of the department that projects are in operation.

19 Overview Annual Report : 2011-12

Biotechnology Industry Partnership for public institution innovation, technology Programme (BIPP) and Biotechnology transfer and acquisition in national priority Industry Research Assistance areas, promotion of entrepreneurship, Programme (BIRAP) incubators, parks and clusters and SME empowerment measure and schemes. BIRAP is well equipped with required staff to execute different programmes on capacity R&D Scheme building. It has initiated electronic journal consortium with the help of DELCON to Efforts continued towards optimization and facilitate access to experts and industry to scaling–up of research leads with an aim over 900 journals and scientific literature towards commercialization of the biotech for necessary research back up. BIRAP has products and process development for the a mentoring programme for supporting benefits of the society. Various schemes travel and other expenses of experts to have been supported on creation of process facilitate access to important workshops, analytical technology based control for meetings and conferences. The Cabinet has downstream biotech processes, use of sub- accorded approval for the setting up of critical CO2 for precipitation and “Biotechnology Industry Research Assistance stabilization of ultra-fine particles of active Council (BIRAC)” under BIPP scheme to pharmaceutical ingredients for support high risk futuristic technology and pharmaceutical applications. Other process development to make India globally approaches include development of competitive in biotech innovation and matrices using polyhydroxyalkanoates from entrepreneurship and to create affordable indigenous Pseudomonas sp. LDC-5, the products and services. BIRAC is being set process optimization for keratinase up as a separate body for supporting production from Bacillus pumilus for product innovation and providing required degradation of recalcitrant proteins, mass infrastructure and services at different stages cultivation of the fruiting bodies of of the value chain for promoting innovation different strains of Ganoderma lucidum at and product development and providing different climatic conditions to formulate funding/investment for early and late stage, Ganoderma powder as potential products of including Small Business Innovation nutraceutical importance and in vitro Research Initiative (SBIRI), Biotechnology biosynthesis of antimalarial drug Industry Partnership Programme (BIPP) and artemisinin via metabolic engineering of Ignition grant, contract research in Industry By-2 cells.

20 Annual Report : 2011-12 Overview

Biotechnological approaches to Food and from the use of Genetically Modified Nutritional Security Organisms (GMOs) and products thereof. A three tier mechanism comprising Severe acute malnutrition is an important Institutional Biosafety Committee (IBSC) cause of morbidity and mortality in at the Institute/company involved in children below 5 years of age in India. An recombinant DNA (rDNA) research, the alliance has been formed among Review Committee on Genetic Departments of Health Research (DHR), Manipulation (RCGM) in the Department Department of Biotechnology (DBT) and of Biotechnology, and the Genetic Ministry of Health and Family Welfare of Engineering Appraisal Committee (GEAC) the Government of India to support in the Ministry of Environment and Forests research to generate evidence for (MoEF) has been established for development of practical and scalable evaluation and approval of rDNA research regimens to medically rehabilitate children and development activities, monitoring suffering from Severe Acute Malnutrition and evaluation and environmental release (SAM) without serious complications at of genetically engineered (GE) crops. home/community level and/or at peripheral inpatient facilities. The Applications in healthcare/agriculture for department has initiated development of import/ export/ exchange of GE materials, indigenous products suitable for for conduct of pre-clinical toxicity studies, rehabilitation of SAM for children and evaluation of pre-clinical toxicity study development of stable and acceptable reports and subsequent recommendations multi-micronutrient and mineral mixture to Drug Controller General of India (DCGI) used as a part of regimes for management for appropriate phase of clinical trials, of SAM. contained/ confined field trials on GE crops etc. were examined by the RCGM and Biosafety Issues appropriate decisions taken. Though cotton is the only GE crop approved for Bio-safety research programmes have commercial release in the country so far, focused on facilitation and implementation several other crops like brinjal, corn, of bio-safety procedures, rules and mustard, sorghum, cabbage, castor, guidelines under Rules 1989, Environment cauliflower, groundnut, okra, potato, rice, (Protection) Act 1986 to ensure safety to tomato etc. are in the advanced stages of the users as well as to the environment development for environmental release.

21 Overview Annual Report : 2011-12

of NEBInet. Three major consortium projects Biotechnology Information on bio informatics in TB, Rice and Mango System Network (BTISnet) have shown excellent progress.

BTISnet has emerged as a potential scientific Biotechnology Parks and network in the country comprising of more Incubators than 165 institutions. In addition to the development of state of art infrastructure and Biotechnology parks have been established human resource, the network has also proved to facilitate product advancement and its capability in carrying out intensive innovation through the development of a research and development activities in biotechnology industrial cluster and to bioinformatics and computational biology. A produce biotechnologists and entrepreneurs compendium on “Research Publications in having strong foundation in research and Bioinformatics and Computational Biology innovation. The incubator facilities help start from India” was released and skilled human up companies, provide support to young resources are being promoted through the entrepreneurs who are not able to invest in long term and short term courses and facilities but have the capability to design trainings. The BINC exam which is considered new products and processes. With many as highly stringent national exam is picking multinational and bio-pharma companies up well and 35 candidates have been initiating their R&D and manufacturing qualified this year and is expected to grow operations in India the demand for biotech more numbers as the syllabus has been fine incubators has increased. Both Central and tuned and courses are being conducted State Governments are making earnest efforts based on the syllabus framed for the BINC to promote biotechnology activities in the exam. Eight new BIF centers have been country by setting up biotechnology parks, added to the BTISnet and in fact the new incubators as well as pilot projects. generation Bioinformatics centres are doing Biotechnology parks and incubation centres exceptionally well and has brought in a lot set up in different states are progressing well. of experimental component to the Bioinformatics. NEBInet comprises of more International Collaboration than 25 Bioinformatics centers in North East states. Several new programmes like biotech International Cooperation is an instrument hubs, overseas associateship, twinning R&D to address global challenges of food, health, etc. are being implemented with the support nutrition and climate change. DBT has

22 Annual Report : 2011-12 Overview

entered into bilateral and multilateral in ‘Systems Immunology and Genetics of strategic alliance with a focus on global Infectious Diseases (SIGID). challenges. These alliances promote scientific excellence through R&D and Autonomous Institutions innovation towards creating opportunities for higher education training and capacity Presently the department has 14 autonomous building. Concerted efforts were made institutions engaged in various activities of towards expansion of strategic bilateral and R&D innovation and excellence at par with multilateral cooperation with Australia, international standard. It allocated about 25% Canada, Denmark, Finland, Japan, Norway, of its total budget during the year for these Sweden, Switzerland, UK, EU and USA. The institutions. The salient achievements are department in partnership with ABLE has highlighted below: successfully conducted Biotechnology Entrepreneurship Student Teams (BEST) National Institute of Immunology (NII), programme for development of enterprise New Delhi amongst young doctoral students and training them in techno-managerial issues. NII, New Delhi continued its activities in A ‘Programme of Co-operation’ (POC) was conducting high-quality research in the area signed between the Republic of India and of immunology and related sciences. The Republic of Tunisia in 2006 for five years in core areas of research include infection and the area of biotechnology with an objective immunity, molecular design, reproduction, to develop and support collaborative development and gene regulation. A research activities in the area of agriculture number of promising leads were reported and health care. The POC was extended on the biology of Mycobacterium tuberculosis. recently for another five years on mutual HisB, an important protein in the histidine- agreement with a commitment to cooperate biosynthetic pathway of Mycobacterium for fruitful outcomes. A ‘Memorandum of tuberculosis was crystallized and preliminary Understanding’ (MOU) signed between India X-ray crystallographic analysis reported. An and CNRS; France was recently renewed agreement was signed with the National with an objective to establish International Cancer Institute in the US for undertaking Associated Laboratories (LIA) in the area of clinical trials at the Sloan Kettering biotechnology as well as to launch a new Memorial Cancer hospital in New York to international Masters’ and Ph.D. programme focus on cervical cancer and check the

23 Overview Annual Report : 2011-12

vaccine efficacy against ovarian cancer. The National Brain Research Centre (NBRC), institute has been involved in clinical trial Manesar, Haryana of rotavirus vaccine developed to reduce the incidence of diarrhoea or its severity in NBRC continued its focused activities on neonatal children. inter disciplinary science from molecular biology and genetics through psychology National Centre for Cell Science (NCCS), to neuro-medicines and bio-engineering. Pune Scientists at NBRC focus on major classes of brain disorders, such as The NCCS has given emphasis in the areas neurodegenerative, neuro-oncological, of cell biology, signal transduction, cancer infective, developmental and neuro- biology, diabetes, biodiversity, infection and psychiatric and conducting research on immunity, chromatin architecture and gene infectious agents including Japanese regulation, stem cell, proteomics, encephalitis, HIV and Prion diseases. As bioinformatics and regenerative biology. It neuron-glia crosstalk is recognized to be also serves as a National Cell Repository pivotal to normal brain functions, the and a training centre for animal cell and NeuroAIDS laboratory has broken new tissue culture. As the National Repository, ground by establishing a well characterized NCCS procures and maintains various cell human neuron-glia co-culture system that lines and distributes them to different is used for unravelling intricacies of neuron- Universities and Research institutions in glia communication. Researchers are India. In the previous year, NCCS supplied expected to develop capabilities with human over 2300 cell lines to 120 organizations. It brain cell culture system to understand is committed to its contribution towards better the HIV-1 proteins that modulate human resource development, by way of neurocognitive functions in HIV/AIDS reaching out to individuals at all levels patients. As a deemed university, NBRC is including students, teachers and researchers continuing its M.Sc. and Ph.D. programmes. in India. The procedures for isolation, expansion, cryo-preservation and Centre for DNA Fingerprinting and differentiation of stem cells into specific cell Diagnostics (CDFD), Hyderabad types have been optimized. The institute is making efforts in understanding the cellular CDFD is continuing its basic research in and molecular mechanisms defining stem related areas along with providing services cell niche in normal organs. for DNA fingerprinting and diagnostics.

24 Annual Report : 2011-12 Overview

The institute is regularly receiving and automated procedure was developed for dealing with the referred cases from the identification of terpene synthase (TPS) or judiciary and law enforcing agencies. prenyl transferase (PT) proteins in plants During this year, the centre provided using Profile Hidden Markov Model. In genetic evaluation and counselling to 1650 chickpea, interspecific linkage map has been patients. 112 cases of judiciary and law constructed for ICCV-2 x JG-62. In the Indo- enforcing agencies examined related to Canadian Pulse Genomics Initiative, a total identification of deceased, maternity / of 536 SSR primers were designed from lentil, paternity dispute and other related criminal of which 196 were validated. In another matters. APEDA-CDFD centre for Basmati legume Trifolium alexandrinum, a microsatellite DNA analysis centre has analyzed 205 enriched library was constructed which led Basmati samples for certifying the quality to the development of 692 SSR markers. It and authenticity of Basmati Rice. The was observed in rice that the induction of institute has taken new initiatives in DNA phytoalexin biosynthesis genes by UV-B rays profiling to demonstrate the power of was linked with the activation of MAP kinase. expanded application of the technology The transgenic tobacco lines over expressing improving the system of criminal justice CaZF produced phenotypes with improved delivery in the country. The Centre has root and shoot growth along with stress signed an MoU with the Institute of Life tolerance. Two stress-inducible promoters Sciences (ILS), Bhubaneswar and the State were evaluated for their activity and raising Government of Orissa, to establish its transgenics with selected target genes. In the laboratory in ILS and collaborate with the nutritional genomics programme, stable lines Government of Orissa to provide DNA of AmA1 potato developed were grown and profiling services in the state. evaluated. The transgenic potatoes have increased protein content and are safe for National Institute of Plant Genome consumption. In rice, functional analyses of Research (NIPGR), New Delhi seed-specific genes and anther-specific gene promoters were undertaken to understand NIPGR is working on computational biology, the crucial controls of reproductive genome analysis, molecular mapping, development connected to the yield. NIPGR molecular mechanisms of abiotic stress researchers published 61 papers in high response, nutritional genomics, plant impact journals. Three patents were filed and development and architecture, plant two technologies developed at the Institute immunity, and other emerging areas. An were transferred for product development.

25 Overview Annual Report : 2011-12

Institute of Life Sciences (ILS), the molecular efficiencies of pathogenic Bhubaneswar isolates of V. cholerae harbouring natural variants of ctxB in causing the disease, The institute continued its focus on suggesting the need to consider ctxB infectious diseases biology, gene function variants in designing vaccines against as well as regulation and translational cholera. research activities. Work on identification and characterization of an immunoregulatory Institute of Bioresources and Sustainable helminth glycoprotein was taken to its Development (IBSD), Imphal logical end. The active moiety that binds to TLR4 on the surface of mononuclear cells IBSD continued its efforts on sustainable and inhibits endotoxemia in animals was utilization of bio-resources focusing on identified to be a hexasaccharide, medicinal, aromatic and horticultural plants, Chitohexose, which offered insights into microbial, aquatic and insect bioresources evolutionary relationship between toward economic development of North East nematodes and sepsis in human population. Region. Germplasm repository of The research on TLR polymorphism in Zingiberales has been further enriched by human filariasis revealed an association of addition of 27 more species raising the TLR2 mutants (ins/ del + del/ del) and collection to 289 accessions belonging to 73 minor allele (del) for increased risk of species. Bambusa manipureana and elephantiasis development. Studies Dendrocalamus hamiltoni have been selected undertaken on pathogen vibrio isolates have as superior edible bamboo due to their low revealed details of genes regulating toxicity cynogenic glycosides content, high and virulence and ability to form biofilms. antioxidant properties and high level of Molecular analysis of toxigenic V. cholerae nutrient content. Kachai lemon found as a strains indicated the presence of multiple potential root stock for production of ctxB genotypes. The comparative modelling budded mandarin orange was studied to approach to define the structural features of increase yield, reduce moisture stress and all known variants of ctxB found in V. Phytophthora disease incidence. A strain of cholerae including 0139 serotypes suggested Bacillus subtilis MTCC 548 from fermented subtle variations in the binding ability of soybean was found to exhibit very high ctxB variants to carbohydrate ligands of GM1 fibrinolytic casenolytic ratio indicating high viz. galactose, sialic acid and N-acetyl affinity to fibrin. A total of 1857 bacterial galactosamine. These findings shed light on strains from NE region soil have been

26 Annual Report : 2011-12 Overview

found to exhibit anti-cancer, anti-diabetic and which is released by monocytes in response anti-inflammatory property. Bio-pesticide to oxidative stress induced by formulations comprising Trichoderma sp T- hyperglycemia. Cyclophilin A (CyPA) is 86 and Pseudomonas fluorescent IE 161 known to have paracrine and autocrine strains have been tested at field level for stimulatory effect on endothelial cells. CyPA the control of soft rot disease in ginger. A secreted by monocytes could have important low cost technique for conversion of floating effects on enhancing monocyte adhesion to aquatic biomasss of Loktak Lake into endothelial cells and thus in the pathogenesis compost was demonstrated to farming of atherosclerosis in type 2 diabetes. Attempts community of Bishnupur district and have been made to understand at the gene training-cum-demonstration programme on level, if timing of surgery during a particular fermented soybean production technology phase of the menstrual cycle plays a organized through KVK, Imphal significant role in survival of a pre- menopausal woman with breast cancer. Rajiv Gandhi Centre for Biotechnology Important molecular events/ patterns that (RGCB), Thiruvananthpuram, Kerala occur might help to determine a long term prognosis by appropriately timing the The major emphasis of the RGCB is on surgery and hence save lives. A number of research programs in Disease Biology and novel mutations, in both structural and non- Molecular Medicine. Employing cutting edge structural protein coding regions, were technologies, the centre is exploring the identified in CHIKV isolates by whole biological systems with a mission to genome sequence analysis. The institute is understand the diseases processes focusing also providing service facilities for molecular on cancer, infectious diseases, neuronal diagnostics for infectious diseases, cancer and disorders, reproductive and cardiovascular cardiovascular disease, DNA fingerprinting diseases. A new program was started in to cater to social and criminal justice systems disease biology of diabetes by taking up the and DNA barcoding for plants and wildlife. management of the Institute of Diabetes, a specialty medical center belonging to the Institute for Stem Cell Science and Government of Kerala. Scientists have Regenerative Medicine (InStem), identified a secretory factor, Cyclophilin A, a Bangalore peptidyl prolyl cis-trans-isomerase in monocytic cells of THP-1 cells as well as InStem has given emphasis on building a from patients with Type 2 Diabetes Mellitus strong foundation for core research and

27 Overview Annual Report : 2011-12

educational activities in the area of stem research activities are focused in three broad cell biology and regeneration. The core areas, namely, vaccine and infectious scientific program was initiated with the diseases centre, paediatric biology centre, appreciation that understanding stem cell and centre for bio design and diagnostics functions will require fundamental development. A Clinical Development investigations into basic, molecular and Services Agency (CDSA) has been cellular processes. Several projects are being established as an extra-mural Centre of pursued collaboratively on protein-protein THSTI. Vaccine and Infectious Disease interactions, quiescence and cell cycle, Research Center (VIDRC) research would signalling pathways, embryonic stem (ES) focus on infectious disease biology, cell self-renewal, RNA biology, chromatin development of animal models, and natural biology and regulatory networks. InStem history of disease in population giving new core group are collaborating with scientists insights into protective host responses and and clinicians internationally and within biomarker discovery for screening vaccine India to work on cardiac function, iPS candidates, for novel vaccine development. technology, biophysics and cell biology to The centre for Bio Design (CBD) has been tackle core problem-generating cellular set up to create medical technology models of cardiac disease. Another focus innovation in India for affordable health care of the institute is on epithelial stem cells and to support services that extend from and development, mechanisms of tumor strategic bench work to commercialization. formation and networks that control The primary objective is to develop a cadre signalling and adhesion in tissue of investigators of global standard in architecture. regulatory product evaluations through a comprehensive and sustained training Translational Health Science and program. Technology Institute (THSTI), Faridabad National Institute of Biomedical Genomics THSTI is an autonomous institution (NIBMG), Kalyani, West Bengal established by the department to conduct innovative translational research and NIBMG was established to provide an develop research collaborations across impetus to research and translation to enable disciplines and professions to accelerate the an understanding of the aetiologies, development of concepts into tangible prevention and treatment of diseases and a products to improve human health. THSTI’s reduction in public health burden.

28 Annual Report : 2011-12 Overview

Inadequacy of formal training programmes of the Biotech Science Cluster (BSC) at in human genetics has been a serious Faridabad, NCR where construction activities impediment to the development of are under progress. Presently it is undergoing biomedical genetics in our country. NIBMG different phases of growth. Currently, the is able to fill this gap by initiating courses centre is functioning from its interim on genetics in medicine. The institute has laboratories. A new Bill has been introduced been able to recruit the faculty and the for the establishment of the Regional Centre faculty members are currently engaged in for Biotechnology, Training and Education as research, training and outreach programmes. Category-II institution under the auspices of Three core areas are developing in NIBMG UNESCO to undertake research in the field of – cancer genomics; genomics of common biotechnology and to provide for matters diseases and traits, including susceptibility connected therewith or incidentally thereto. to infections; and statistical and population The Regional Centre having the futuristic genomics. The Institute has successfully vision of providing biotechnology education, generated eight competitive extra-mural training and research is planned to be within research grants, including one from the U.S. Biotech Science yet broad-based and multi- National Institutes of Health. NIBMG has disciplinary. Its proposed research and developed collaborations with many educational activities are focussed to be at national and international institutions, the interface of different disciplines of science including medical colleges and hospitals. with Biotechnology as a platform of The Institute’s flagship project, the confluence. Attempts are being made to International Cancer Genome Consortium – establish a wide range of disciplines that India Project, is progressing well. This include Biomedical Sciences, Bioengineering, project attempts to identify genomic Biochemical and Biophysical Sciences, Climate alterations that cause gingivo-buccal oral Science, Agriculture and Environment, cancer, which has the highest prevalence in Biotechnology Regulatory Affairs, IPR and India, using massively-parallel next- Policy. generation DNA sequencing technologies. National Agri-Food Biotechnology Regional Centre for Biotechnology (RCB), Institute (NABI), Mohali, Punjab Gurgaon NABI has taken new initiatives to study the RCB was established under the auspices of effect of diet and its constituents on UNESCO to be an important member institute adipogenesis. Fractionated constituents of

29 Overview Annual Report : 2011-12

selected cereal grains (wheat, finger millet, and improved therapeutic molecules for farm kodo millet and buck wheat) is being animals along with promotion of bio- examined in human (preadipocytes/ entrepreneurship for farm animal based adipocytes) HPAd/ HAd and murine (3L3- products. To initiate R&D activities NIAB L1 preadipocytes/adipocytes) cell culture has hired a building very close to the site models and in-vivo diet-induced obese allotted to NIAB and the recruitment process murine models to study the molecular basis for scientific, technical and administrative of adipogenesis. Another study was targeted positions is in progress. on mutagenesis for modification of plant genes to design sequence specific zinc finger Bio-clusters nucleases (ZFNs), synthetic proteins consisting of an engineered sequence The department has established a Biotech specific zinc finger DNA-binding proteins Science Cluster at the NCR region of Delhi. used to induce double-stranded breaks The heads of four founding institutions (DSBs) in specific DNA sequences and namely, the National Institute of Immunology; thereby promote site-specific recombination the Regional Centre for Biotechnology; the and targeted manipulation of genomic loci Translational Health Science and Technology in a variety of different cell types for Institute and the National Institute for Plant developing novel traits in crop plants. Genome Research signed a MoU to create a new entity called the Cluster Board. The National Institute of Animal Cluster Board is an enabling mechanism by Biotechnology (NIAB), Hyderabad which these institutions, while maintaining their own autonomy can address not only NIAB, a new autonomous institution of DBT, common infrastructural and cluster-related is being established within the campus of administrative issues but also synergize their the University of Hyderabad. The institute is complementary intellectual strengths and aiming to harness novel and emerging facilities to create a seamless campus. This biotechnologies and take up research in the Cluster will coordinate the development of cutting edge areas for improving animal the new campus at Faridabad. Efforts are health and productivity. It focuses research being made to create this Cluster as a legal on infectious diseases, breeding, reproduction entity. A “Centre for Molecular Medicine” has and nutritional enrichment and aims at been established at this Cluster. The focus of translational research leading to the this Centre is on infectious diseases, cancer, development of novel vaccines, diagnostics cell therapy and drug design.

30 Annual Report : 2011-12 Overview

The Bangalore Bio-cluster comprises the The Indian Vaccines Corporation Limited National Centre for Biological Sciences (IVCOL) was started as a joint venture (NCBS), the Institute for Stem Cell Biology company to undertake research and and Regenerative Medicine (InStem) and development and manufacture of viral Centre for Cellular and Molecular Platforms vaccines. Concerted efforts have been made (C-CAMP). These three institutions are to finalize the restructuring process with new interacting, sharing knowledge and resources activities. After taking necessary approvals on a regular basis to enrich research. C-CAMP from competent authority the company has is acting as provider, developer and enabler signed lease agreement with IPCL/Reliance of technology development, scientific activity Lifesciences, one of the promoters of the and entrepreneurship. This is an institutional company, to initiate new activities including model for cutting edge scientific research production of vaccines, biopharmaceuticals aimed at utilizing various centres of and set up superspeciality hospital to initiate excellence for developing new hubs. InStem translational research in collaboration with is developing collaborative programmes with NBRC. To initiate the proposed activities, other institutes utilizing the infrastructure and Reliance Life Sciences (RLS) finalized the facilities available in the Cluster. master plan for setting up integrated life science unit along with a super specialty Public Sector Undertakings hospital for neuro and cardio at Manesar.

Bharat Immunologicals and Biologicals International Centre for Genetic Corporation Limited (BIBCOL) were Engineering and Biotechnology established to manufacture Oral Polio (ICGEB), New Delhi Vaccine (OPV) to meet the tOPV requirement for Universal Immunization ICGEB is promoting high quality basic Programme (UIP) of Government of India. research and training of young scientists in The company established in the Technology broad areas of genetic engineering and Mission of Immunization to achieve self biotechnology including infectious diseases, sufficiency for the nation with respect to agriculture and bio-energy. Several new production and supply of high quality OPV, initiatives were undertaken during the last contributed significantly to the eradication one year through funding from different of Poliomyelitis in the country through sources including funding from DBT for Pulse Polio and routine Immunization Center of Excellence (CoE) and Bill Gates Programmes. Grand Challenge Exploration grant for the

31 Overview Annual Report : 2011-12

second phase of research. The Malaria Group genomes for identification of proteins that received CoE funding to undertake novel could be useful as insecticidal agents and interdisciplinary approaches using cutting two pro-region peptides that specifically kill edge technology to address important neonate larvae of Helicoverpa armigera have problems in the biology of blood stage been identified. The ICGEB has filed 8 malaria parasites which will generate crucial patents, developed 3 technologies along with field data that will help in designing a malaria 120 publications in high reputed journals vaccine for the Indian population. The during the year. Virology Group, focusing on hepatitis viruses, HIV, Influenza virus and multiplex Promotion of Biotechnology in virus detection strategies, initiated a study the North Eastern States of India during the last year to understand the role of oncogenic viruses (using hepatitis B virus The department has followed the government as a model) in regulating origin licensing as policy of contributing 10% of its total budget a model for cellular transformation. The DBT for the year 2011-12 to promote Biotechnology has recently approved and funded the activities in the North Eastern Region of India. extension of Centre of Excellence Program The department has taken several new major on TB research into Phase-II to develop novel activities for the benefit of North East States. intervention strategies for tuberculosis. A new Under Twining R&D programme a total of initiative was undertaken by DBT and ICGEB 117 proposals have been approved towards to establish a DBT-ICGEB Centre for integrated technology and product Advanced Bioenergy Research at ICGEB New development. More than 1400 farmers have Delhi to take the bioenergy research to a been trained on organic farming technology greater height. The DBT-ICGEB collaborative using bio inputs for 9 horticultural groups. centre shall be expanding its activity towards A Consortium project on biotech intervention genomic, metagenomic, synthetic and systems on selected medicinal and aromatic plants of biology areas for addressing some of the NER for their effective utilisation has been key issues of biofuel development such as implemented. Towards institutional capacity finding efficient cellulolytic enzymes, building the department launched several developing biocatalysts for C5/C6 innovative programmes under which so far fermentation, generating advance biofuel more than 90 Biotech Hubs have been molecules, and developing robust algal established at various institutions of eight strains for biodiesel production. NER States. NEBInet is spreading across the Investigations continued for exploring insect North Eastern Region with more than 25

32 Annual Report : 2011-12 Overview

Bioinformatics centres providing lot of new collection of body substances; to establish a avenues in the Biological Sciences for this National and /or State DNA Data Bank/ region. Altogether 15 institutions are a part Banks; to create policies for use and access of NER DeLCON for accessing more than to information from data bank, etc. and for 900 important journals. Through a special matters connected therewith or incidental programme DBT has supported more than thereto. The Draft Bill was circulated to the 50 NER Scientists with Overseas ministries concerned and departments of the Associateship for undertaking research central government to obtain their comments trainings in abroad. The DBT AAU Centre and has been revised, wherever necessary, which has been established at AAU, Jorhat keeping those comments in view. Draft Bill has shown excellent progress towards R&D has been sent to the chief secretaries of all in crop sciences, human resource the states for information and feedback. development and promotion of technology. Under the capacity building of NER Regional Centre for Biotechnology (RCB) Bill programme a number of lab staff and PI is for an international nodal point for have received short-term training in leading biotechnological sciences at the interface of research labs in the country and a number of multiple disciplines that would be an workshops and symposia have been autonomous body under statute of organized in the region. A series of hands- parliament as an institution of international on wet lab workshops are planned for the importance for biotechnological education, year 2012 to provide training in molecular training and research. A new Bill has been biology, medical genetics and immunology. introduced for the establishment of an institution of national importance to be New Legislations and known as the Regional Centre for Regulations Biotechnology, Training and Education as Category-II institution under the auspices Human DNA Profiling Bill has been of UNESCO to undertake research in the formulated by the department in field of biotechnology and to provide for consultation with the Centre for DNA matters connected therewith or incidentally Fingerprinting and Diagnostics, Hyderabad, thereto. to regulate the use of DNA analysis of body substance profiles; making provision for Biotechnology Regulatory Authority of India establishment of DNA Profiling Board to (BRAI) is proposed as an independent, lay down standards for laboratories, autonomous, statutory agency to be

33 Overview Annual Report : 2011-12

established through the Act of Parliament department rendered support in the by the Government of India to safeguard implementation of various programmes. the health and safety of the people of India Modern multimedia equipment were and to protect the environment by procured and installed for effective identifying risks posed by, or as a result of, presentation. An effective video conferencing modern biotechnology and managing those system has been operational in the risks through regulating the safe department. To keep pace with the growth development and deployment of of the department, new positions of biotechnology products and processes. The scientists and other technical staff created Authority will be responsible for regulating last year were fulfilled. Scientists/Staff were the research, transport, import, manufacture also deputed for various training and use of organisms and products in health programmes to enhance their skills in care, agriculture, veterinary and relevant areas. The department also environment. The BRAI Bill after cabinet participated in extracurricular activities and approval has been sent to the Lok Sabha for performed well in various events. A Hindi introduction. fortnight was organized in the Department from 14th-30th September, 2011. The Administration and Finance department was allocated under budget estimates an amount of Rs.1400 crores for Administration and finance divisions of the the year 2011-12.

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34 Chapter 2

HUMAN RESOURCE DEVELOPMENT

Skilled manpower is an important key Teaching component for the scientific and socioeconomic development of the country. Post Graduate degree program (M.Sc./ For achieving of this objective, the M. Tech./M.VSc.) Department of Biotechnology (DBT) is implementing an integrated human resource Department initiated postgraduate teaching development program in biotechnology programs in six universities in 1985-86 to comprising of postgraduate teaching ensure high standard of teaching and to program, doctoral & post-doctoral fellowship generate critical mass of trained manpower and specialized training program for UG and in country. The programs have been PG teachers and mid-career scientists. The expanded to 70 universities keeping in mind Department is providing industrial training regional distribution of universities, need to biotechnology students to develop skills for general and specialized courses such as required for biotech industries in country. agricultural, medical, pharma, food, The Department has initiated Star College veterinary, industrial biotech etc. Location Scheme for improvement of hands on training of institutes running these programs is for undergraduate science students by depicted in Figure 2.1 & 2.2. Students for providing support for infrastructure DBT supported teaching programs are development with emphasis on faculty selected on All India basis through common training pursuing, projects of day to day entrance test conducted by JNU at over 70 relevance and industrial exposure to centres in all parts of country or IIT-Joint undergraduate students etc. A few new admission test or University examination initiatives viz., an online system for feedback test. Selection process is very stringent and by students of DBT supported teaching approximately 1 out of 60 applicants is program and setting up of Biotech education selected. All selected students are paid and skill development council are under studentship. Department is developing an consideration of the department. Significant independent on-line feedback mechanism by achievements under different programs are students for DBT supported teaching given below: programs.

35 Human Resource Development Annual Report : 2011-12

Department provides grants for purchase of Sciences & Technology of Kashmir, equipment routinely required for class room Shuhama, Srinagar, J & K is under process teaching and liberal recurring grant for for providing financial support. consumables, books and journals, travel, contingency, equipment maintenance grant, summer/winter training. It has been mandatory to have in-house dissertation and department is providing thesis grant of Rs. 50,000/- per student to ensure their practical training. A few research articles and reviews in journals of national and international repute have come out as a result of dissertation of M.Sc./M.Tech. students. During 2011, a program in Medical Biotechnology has been sanctioned to M.D. University, Rohtak and proposal for starting M.V.Sc. in Animal Biotechnology course at Fig. 2.2. Map showing location of Universities/institutes Sher-e-Kashmir University of Agricultural running DBT supported M.Tech and M.VSc. programs

Monitoring of PG teaching programs & ranking of Universities/institute running DBT supported PG programs:

To ensure uniform standard of teaching, DBT sponsored teaching programs are periodically reviewed by expert committees viz., in-house advisory committee, course coordinators meeting and DBT–HRD Task Force. The progress of DBT supported post graduate teaching programs has been evaluated based on number of criteria such as core faculty strength, mode of admission, filling up of sanctioned seats, in-house dissertation, Fig: 2.1. Map showing location of Universities/institutes running DBT supported M.Sc. programmes placement of students publications during

36 Annual Report : 2011-12 Human Resource Development

last five years, infrastructure created, R & D projects of day to day relevance have grants received by their department etc. enhanced interest among students to pursue Mentors have been identified for programs science courses. ranked low to help them to improve. During 2011, advertisement seeking Star Colleges proposals from colleges in North Eastern Region was issued and 17 new proposals “Star College Scheme” has been initiated by were received. In response to another call DBT to support colleges and university for proposals from all parts of country, 38 departments offering undergraduate new proposals were received which have education in life sciences to improve been evaluated by expert committee. To teaching of biotechnology component. The monitor the progress of colleges supported programme aims to improve the skills of under the scheme, mentoring committees teachers by organizing faculty training, have been constituted to provide guidance, improved curriculum and emphasis on formulate and implement detailed plan and practical training to students by providing give suggestions to identify the access to specialized infrastructure and shortcomings and gaps to strengthen the consumables. Star college scheme has been ongoing colleges. divided in two categories viz. strengthening of support for undergraduate education and Star college status. Criteria for selection as a “Star College” are very stringent and budget provision is double for colleges accorded star college status. One time non-recurring grant for equipment and annual recurring grant is provided for life science departments in selected colleges. So far, 56 colleges have been supported under the “strengthening of support” category (Figure 2.3). None of the colleges have been accorded “Star College” status. The support has strengthened physical infrastructure in laboratories, library, teaching aids, and promoted networking with Fig 2.3: Map showing location of colleges supported neighboring institutes. Hands-on training and under Star College Scheme

37 Human Resource Development Annual Report : 2011-12

implemented through Biotech Consortium Training Programmes India Ltd., New Delhi. BITP provides industry-specific training to Biotech students Short term training courses for mid- for skill development and enhancing their career scientists, faculty involved in job opportunities in biotech industries undergraduate and postgraduate teaching engaged in R & D, quality control & analysis, production & manufacturing, marketing, DBT is supporting a number of short term regulation and IPR. This program has training courses for mid-career scientists, completed 22 years and has become faculty involved in undergraduate and increasingly popular among students (Figure postgraduate teaching for upgrading skills 2.4). There is a stringent process for screening of existing people. During 2011, 41 and selection through interview by expert proposals were received and 19 were committee comprising of representatives from recommended for financial support by academic and industries. 652 candidates expert committee. These courses are trained in 146 biotech companies (Annexure- extremely beneficial in upgrading skills of II). About 25-30% students trained under this existing faculty. These specialized courses program are offered regular placement. 150 are organized in premier research industries are involved in training. There is institutions for duration of 2-3 weeks for provision to place 700 candidates in 12-15 participants and provide hands on industries during 2011-12. exposure to UG and PG faculty and mid career researchers on latest techniques. The list of the courses conducted during the year with support from the department (Annexure-I).

Biotech Industrial Training Programme

Fig. 2.4 : Number of applicants and selected candidates Biotech Industrial Training program (BITP) for industrial training during last five years was initiated in 1990 for providing 6 months industrial training to fresh M.Sc./M.Tech Student Research Projects biotechnology students. The program has been extended to B.E./B.Tech biotechnology Department of Biotechnology jointly with students from 2007. The program is being Tamil Nadu State Council for Science and

38 Annual Report : 2011-12 Human Resource Development

Technology is supporting student research accounting, statutory and legal requirement. projects to develop and utilize the An entrepreneurship development program tremendous talent and potential of students (Phase II) for advance training and setting and train them for solving specific scientific up small biotech industry in North Eastern and technological problems relevant to region has been sanctioned to Biotech society. Under this Scheme, financial Consortium India Ltd, New Delhi. This support is provided to encourage the U.G. program is designed to provide the (Engineering) and PG students (Bio- entrepreneurship development training, all engineering / Physics / Chemistry / the technical assistance and hand holding Medicine / Agriculture / Veterinary / support for enabling entrepreneurs to set Environment / Social Sciences) enrolled in up successful industrial units in areas such colleges and universities to take up useful as (i) Aromatic & Medicinal Plant Extraction minor research projects as dissertation work. (ii) Micropropagation (iii) Bio-fertilizers and Candidates present their findings before an Biopesticides (iv) Orchid culture and (v) expert peer group in a seminar cum Aquaculture/Probiotics. exhibition. Selected projects and models are awarded. Fellowships

Entrepreneurship Development DBT Junior Research Fellowship (DBT- Programme (EDP) in Biotechnology JRF) Program

Department is providing support for DBT JRF programme was initiated in 2004 organizing EDP workshops in to provide fellowships for biotech students Biotechnology for setting up of new viable pursuing research in universities and / or biotech enterprises by prospective research institutions in the country. Students entrepreneurs in North Eastern region. A are selected through Biotechnology three day workshop was organized in Eligibility Test (BET) conducted at ten Guwahati by Association of Biotechnology centres by University of Pune. Fellowship Led Enterprises (ABLE) which was attended is provided in two categories: Category A by 44 participants. Training mainly focused and B. Category A fellowship: Top 100 on awareness of biotech entrepreneurship students can avail fellowship in any including overview of Indian biotech sector, University/Institute in India. Category B IPR and patenting, HR aspects, business fellowships (150 in numbers) can be availed plan, funding and financing, basic of at the DBT-Supported University/Institute

39 Human Resource Development Annual Report : 2011-12

conducting teaching programs or any of DBT interview. The fellows find placement in autonomous Institutions. The program has leading academic and research institutions become increasingly popular with students in the country. The program is fairly as is evident from increased number of popular with the students as is evident from applicants during last few years (Figure 2.5). increase in number of applicants over last few years while its selection process is very transparent and stringent (Figure 2.6).

Fig. 2.5. Number of applicants for DBT-JRF during last Fig.2.6 : Number of applicants and selected candidates five years for DBT-RA during last five years

DBT Research Associateship (DBT- RA) DBT-TWAS Fellowship Program The DBT-TWAS (Third World Academy of DBT Research Associateship program was Sciences) Fellowship Programme for Post initiated in 2001 to train post-doctoral Graduate Research offers two categories of students in frontier areas of research in fellowship (Regular and Sandwich) to young Biotechnology and life sciences at premier scientists from developing countries other institutions in India and is being than India who wish to obtain all or part of implemented by Indian Institute of Science, their Ph.D in biotechnology. While the Bangalore. The fellowship is initially regular programme is for those desiring to awarded for a period of two years and can register for Ph.D in an Indian University, be extended based on review of progress. the sandwich fellowship is intended for There is a provision for 100 fellowships per applicants who have registered for Ph.D in year. During the year 2011, in response to their own country and would like to get two advertisements, 354 applications were advanced training in their field of received and 80 candidates were selected specialization from an Indian research out of 170 candidates who appeared for institute / university. This fellowship grant

40 Annual Report : 2011-12 Human Resource Development

is for a minimum period of 12 months and candidates have come from USA, 7%, UK, a maximum period of two years. CICS, Canada 4%, Germany 3%, and 1-2% from Chennai has been co-ordinating this activity. The Netherlands, Ireland, France, Italy, During 2007-10, nine Post Graduate and one Singapore, Switzerland, Australia, Japan etc. Post Doctoral fellowship were awarded. Most of the candidates selected are in the Five of the awardees have completed the age group of 31-40 years. training successfully and also obtained their Ph.D degree. Tata Innovation Fellowship

Ramalingaswami Re-entry Fellowship The DBT initiated “Tata Innovation Fellowship” scheme in the year 2006 to The scheme was initiated in 2006 by the reward the scientists engaged in innovation department for scientists working in in the pursuit of path breaking solutions to overseas Institutions/ Universities who major challenges, interdisciplinary work and would like to return to India to pursue an emphasis on translational research in life their research interests. Under the scheme sciences, agriculture, biomedical science and each awardee receives a fellowship amount related areas of biotechnology. The awardees of Rs. 75,000/- pm from (consolidated), are provided a fellowship of Rs. 20,000/- House Rent Allowance @ Rs. 7,500/- pm per month in addition to regular salary and (consolidated). The host institute where they contingency grant of Rs. 5,00,000/- per take up the fellowship may consider giving annum. The duration fellowship is initially other benefits provided to regular faculty for three years, extendable further by two of the institute. So far 97 scientists from years on a fresh appraisal. During the current overseas institutions have been awarded this year four scientists were selected for the fellowship and 75 have already relocated to award of the fellowship. So far, 23 scientists Indian host institutions. There is a provision have been awarded the fellowship. of selecting up to 50 fellows per year. This scheme has been very well received by the Biotechnology Career Advancement and scientific community and more and more Re-orientation Programme for Women scientists are interested in returning to the Scientist (Bio-CARe) home country. This year 50 candidates have been selected. Nearly 50% of the candidates In an attempt to enhance the participation selected have joined as faculty at same or of Women Scientists in Biotechnology different institute. 74% of the selected Research, the Department of Biotechnology

41 Human Resource Development Annual Report : 2011-12

launched a Biotechnology Career like to change their career path to take on Advancement and Re-orientation newer areas. Specialized skills would be Programme (Bio-CARe) for women essential and this would require training in scientists. The programme is mainly for the relevant field such as – IP management, Career Development of employed/ Bioinformatics, Policy research and analysis, unemployed women scientists upto 55 years Translational research, Regulation etc. The of age for whom it is the first extramural training cost are borne by the Department research grant. The scheme is open for all upto maximum amount of Rupees one lakh areas of Life Science / biology (including on this training could be for a period agriculture, veterinary science and ranging from 3 months -12 months. Under medicine). this scheme the women scientists who are unemployed will be provided a stipend of There is a Research Grant Opportunity Rs.25,000/- p.m. and employed scientists (RGO), under which a 3-5 year research grant will get an amount of Rs.5,000/- p.m as an is provided. The purpose is to build incentive in addition to their salary. capacities for women scientists employed fulltime in Universities and small research There was an encouraging response and laboratories or unemployed women scientist nearly 1000 applications were received. after a career break so as to help them Candidates short listed based on scientific undertake independent R&D projects. Under merit, academic qualification, publications this scheme the women scientists who are were selected under the scheme. Forty three unemployed will be provided a monthly Women Scientists have been awarded the emoluments ranging from Rs. 35,000/- to BioCARe Research Grant Fellowship 45,000/- p.m. The employed women during the year in all areas of Life Science/ scientists in addition to salary will get an biology. Early Career Fellowship for Women amount of Rs.5,000/- p.m as an incentive. Scientists who have completed their Ph.D A research grant of Upto Rs. 50.00 lakhs is during last two years are also being provided considered to help them undertake independent R&D projects. 45 women In addition there is a Career Re-orientation scientists have been awarded the fellowship Fellowship (CRF). This scheme is mainly during the year. for women scientists who are trained in a particular area, but leave their permanent Mentorship Workshops were organized in jobs / or are unemployed and would now four regional centers for Women scientists

42 Annual Report : 2011-12 Human Resource Development

to help them to improvise their project appeared for interview and 10 candidates plans and details. The workshops would have joined the RA program. Biotech also capacitate the women scientists in good Industrial Training Programme for North grant writing and bring confidence to apply Eastern region offers industrial training to for Research Grant to different agencies. fresh B.Tech /M.Sc./M.Tech students in Nearly, three hundred fifty scientists have biotechnology in industry for a period of 6 benefited from these workshops. months. This program is implemented by Biotech consortium India Limited, New Distinguished Biotechnologists Research Delhi (BCIL). Advertisement for seeking Professorship applications has been inserted in national dailies for candidates from North Eastern Under the scheme “Distinguished Region. There is provision to place 100 Biotechnology Research Professorship” candidates in industries for 6 month during launched by DBT during 2008-2009 to the year. recognize eminent scientists who had superannuated and have made outstanding DBT Scholarships and Awards contribution in their respective fields four distinguished Professors selected earlier are Biotech Product, Process Development availing the scheme. This scheme comprises and Commercialization Awards of an award of Rs.60,000/- per month and a research grant upto Rs.20.00 lakh for a period DBT gives awards in recognition of of five years or till the awardee attains the outstanding contributions of scientists / age of 70 years whichever is earlier. innovators / entrepreneurs / Indian institutions & companies both in public Programmes for North Eastern Region as well as private sector for a new process, product development and The Department has started DBT-RA commercialization of a technology or a programme for students from North East product in the areas of biotechnology and region (domicile or have studied for past 3 biological sciences including agriculture, years in university / institute in North biomedical and environmental sciences. Up Eastern states). The program is being to five awards are given every year. Each implemented by Indian Institute of Science, award carries a cash amount of Rs. 2.00 Bangalore. During the year, total 20 lakh along with a citation. Rs. 5.00 lakh applications were received, 12 applicants would be given if the product is

43 Human Resource Development Annual Report : 2011-12

commercialized and has much higher along with citation and a medal. National impact of utilization in the country. The Women Bioscientists Award for year 2011 awardee should be a citizen of India, and is in progress. Indian institution or an Indian company actively involved in the development of National Bioscience Award for Career biotechnology processes and products and Development commercialization of technologies or product based on indigenous research. National Bioscience Awards for Career During the year 2011, out of 12 nominations Development are awarded in recognition of received, one awardee was selected for the outstanding contributions of young scientists Award of Rs. 2.00 lakh. below 45 years of age in basic and applied research in the areas of biosciences and National Women Bio-scientists Award biotechnology including agricultural, biomedical and environmental sciences with The National Women Bioscientists Awards potential for application/product and are given every year under two categories. technology development. Each Award These are (i) National Women Bioscientists carries a cash prize of Rs. 1.00 lakh and a Award (Senior Category) (One) –awarded citation along with project research grant of to senior woman biologist for life time Rs. 9.00 lakh @ Rs. 3.00 lakh per year for a contributions, who has done excellent period of three years for career research work in the country and has development. Upto 10 Awards are given applied the results for the benefit of every year, subject to the availability of students and society, and (ii) National suitable candidates. Out of 55 nominations Women Bioscientists Awards (Young received, 10 awardees were selected for the Category) (Two) – given for outstanding year 2011. contributions of women scientists below 45 years of age in basic and applied research DBT Biology Scholarship in the areas of biosciences and biotechnology including agricultural, DBT Biology Scholarships are awarded to biomedical and environmental sciences with students from the combined merit list of potential for product and technology Biology/ Biotechnology at Higher development. Contribution made during Secondary/Intermediate/ 10+2 level each last 5 years, is the main consideration. Each year to encourage students to pursue Award carries a cash prize of Rs. 1.00 lakh studies in biological sciences after 10+2

44 Annual Report : 2011-12 Human Resource Development

level. From year 2007-08, the amount of awarded and are pursuing excellent scholarship has been enhanced to a innovative research independently which are lumpsum @ Rs. 20,000/- per scholarship being reviewed every year by the IYBA and the total number of students has also expert committee. These awardees have been increased to 100 i.e. 44 students from published 18 publications in indexed Central Board of Secondary Education journals showing the impact factor greater (CBSE), 4 from the Council for Indian School than 7, out of which one publication in Certificate Examinations (CISCE) and 52 Nature Nanotechnology has the impact from State Boards (2 scholarships each from factor 26.31. 26 State Boards). The Award also carries a medal and a certificate of merit. For the A total of 127 applications were received year 2010-11, 89 Students (43 scholarships for the year 2011 awards. The short listing to students from CBSE, 4 scholarships to was carried out through online with the students from CISCE and 42 scholarships to IYBA Experts and out of 110 eligible students from State Boards) were selected candidates, 52 were short listed based on for the DBT Biology Scholarship, while for the scoring of marks of 40% & above and the year 2011-12, details from State Boards 17 candidates were selected for the IYBA are being obtained. Awards.

Innovative Young Biotechnologist Award Rapid Grant for Young (IYBA) Investigators (RGYI) Scheme

The Innovative Young Biotechnologist Rapid Grant for Young Investigators fosters Award (IYBA) scheme was instituted by creative research in various fields of DBT in the year 2005. The award is an biotechnology (Medical, Agriculture, Animal attractive career oriented scheme to identify Biotech, Environment and Industry etc.) to and nurture outstanding young scientists enhance early career development of young with innovative ideas and desire to pursue investigators below 40 years of age. The research in frontier areas of biotechnology. programme aims to provide first grant to This award provides an excellent establish the lab and initiate research in the opportunity for the young scientists who frontier areas of biotechnology. The scheme wish to start research carrier even if they is under implementation since 2005-2006, it do not hold a regular position. So far in was initiated with an endeavor to release last six years, 61 young scientists have been funds to young investigators within eight

45 Human Resource Development Annual Report : 2011-12

weeks of the submission of the proposal. (DBT-CREST Award). Under this programme Under this scheme numerous young 57 candidates were selected for the award investigator have been supported. RGYI has of fellowship during 2011-12. 50 fellowships been receiving overwhelming response are proposed to be awarded during the next through “Call for Proposals” and more than financial year 2012-13. 2000 proposals have been received and about 320 projects recommended and Biotechnology Entrepreneurship sanctioned by the department based on Student Teams (BEST) merit for implementation. RGYI has provided start-up grants to young In an effort to encourage enterprise and investigators across the country working in entrepreneurship the Department with ABLE different settings such as central government has initiated Biotechnology funded institutions, State Government Entrepreneurship Student Teams (BEST) funded University departments, scientists at programme. The programme aims to DSIR approved private institutions etc. encourage young doctoral students in About 100 proposals were evaluated and developing biotechnology entrepreneurship significant progress was observed in various and exposing them to issues involved in projects supported on various priorities commercialization of bio-science. They are research areas. encouraged in a competitive mode, to submit as teams business plans for scientific Cutting-Edge Research Enhance- ideas which can be commercialized. ment and Scientific Training Award (DBT-CREST Award) About 200 concepts were received and top 21 teams were selected for a 4 day In keeping with the advancement of global residential workshop on the topics like- networks for the development of science Role of the Entrepreneur, Qualities of an and the Department’s priority toward Entrepreneurial Mind, Intellectual Property capacity building in human resources, the - Protecting Your Idea, Teams to analyse ‘Biotechnology overseas associateship the market opportunity of their own plans, award’ and ‘Associateship for specialized Plenary – Market Opportunity, Validating training of young scientists’ in niche areas the Market Opportunity etc. of biotechnology has been revised and renamed as the “Cutting-edge Research A jury comprising academicians, managers, Enhancement and Scientific Training Award” entrepreneurs, industry and investment

46 Annual Report : 2011-12 Human Resource Development

groups choose for best teams. First prize Online Submission and Monitoring System was secured by Sastra University, (OSMoSys) helps expediting the release of Thanjkavur; second prize by ICGEB, Delhi grants in aid to the beneficiary institutions and third prize was shared by IIT, Bombay to promote Bio-Technology in India. TERI and ICGEB, Delhi has been selected as an associate partner to carry out the management of this program Biotech Popularization and as a complete out-sourcing assignment Promotion includes development, hosting, adminis- tration, maintenance of the system and Online System for Financial Support to operating it for three years. Conferences, Travel, Exhibitions & Popular Lectures (CTEP) The system has automated processes of proposal submission till the release of fund The department in addition to funding for financial support to the applicant’s research projects on biotechnology and organization. The online system is hosted at related subjects has been encouraging URL (http://www.dbtctep.gov.in) enabling research professionals, academicians and applicants to raise proposals to DBT seeking students to enable them to organize financial assistance for organizing conferences, participate in international Conferences; Seminar; Symposia; Workshop, events, arranging lectures by eminent Travel support for presenting research papers scientists and promoting exhibitions in in the International Conferences which are the subject of biotechnology. DBT being held outside India. earmarks a sizeable budget towards organizing these activities annually. The Proposals are also invited for organizing scheme has been renamed as Conference, exhibitions and arranging popular lectures Travel, Exhibition and Popular Lecture within India. Instructions for each type of (CTEP). proposal are provided to users to facilitate successful submission of proposals to DBT. Keeping in mind the objective of providing The following four types of online application easy access to the professionals throughout forms are available to seek grant from DBT. the country to these grants, DBT has automated the entire operation through the • Financial assistance for holding on-line system named OSMoSys (Online national/ international Conference/ Submission and Monitoring System). Seminar/ Symposium/ workshop

47 Human Resource Development Annual Report : 2011-12

• Travel support for attending management of this program. From January international conference/seminar/ 2011 to December 2011, the online system symposia/workshops has received 361 proposals for Conference support while 739 proposals for Travel • Participation charge in organizing Grants and 7 proposals for popular lectures exhibition by DBT out of which 255, 491 and 7 proposals were supported respectively. Support has also • Financial assistance for organizing been provided to DBT funded institutions popular lectures on Biotechnology by for celebration of National Science Day 2011. experts Moreover, the department participated in 3 exhibitions in India and represented India The TERI, New Delhi has been identified in the India International Trade event held as an associate partner to carry out the in Washington D.C, USA.

Fig. 2.7: Departmental participation in International Trade Exhibition held in Washington D.C, USA ❖ ❖ ❖

48 Chapter 3

BIOTECHNOLOGY FACILITIES, TECHNOLOGY PLATEFORMS AND RESEARCH RESOURCES

each Nistari and CSR-2 and six of their Centres of Excellence (COEs) in hybrids (polyvoltine x bivoltine) in Biotechnology silkworm using RNAi approach have been generated. Multilocational field trials of the The programme provides a flexible model transgenics are planned to be undertaken of long term support for highly innovative after obtaining RCGM clearance. Four viral research, both basic and translational to miRNA have been validated for their create high quality state of art facilities for possible involvement in inter-pathogen R&D and promote quality publications and interaction. Two downstream regulators of intellectual property. During the year a total sex-deterimination pathways genes in of 126 letters of intent/ concept were mulberry silkworm (Bombyx mori) and non- received in response to the call for mulberry silkworm (Antheraea assama and establishment of Centres of Excellence A. mylitta) have been characterized in through an open advertisement. Six new silkmoths. proposals funded under the “Programme Support” and two new proposals were Co-ordinated research on tuberculosis under the category of Outstanding Scientist Research Programme. In a collaborative project on tuberculosis The salient achievements of the “Center of research implemented by International Excellence” supported so far are as follows: Centre for Genetic Engineering and Biotechnology, New Delhi and University Genetics and genomics of silkmoths of Delhi South Campus, New Delhi, several Mtb target proteins were shown to be In a network programme on Genetics and essential for growth for pathogen and animal genomics of silkmoths implemented by models. An auxotrophic mutant of CDFD, Hyderabad, Andhra Pradesh State Mycobacterium tuberculosis with multiple gene Sericulture Research and Development disruptions as a vaccine candidate has been Institute, Hindupur and Seribiotech Research developed and evaluated for its efficacy in Lab, Bangalore, three transgenic strains of animal models. About 25 druggable targets

49 Biotechnology Facilities, Technology Annual Report : 2011-12 Plateforms and Research Resources have been identified. Various inhibitors antibiotics and designing strategies for against three of these targets have been antibiotic peptidomimetics using surrogate tested in collaboration with an industrial receptors of peptide / glycopeptide partner – M/s Sphaera Pharma. antibiotics of intake immune origin has been elucidated. A BSL-3 Containment Facility has been established at University of Hyderabad High-throughput allele determination campus which is undergoing testing for for molecular breeding certification. Immunomodulatory role of a novel protein-chorismate mutase essential At ICRISAT, Patancheru, Andhra Pradesh for survival of Mycobacterium tuberculosis has SNP genotyping platforms for molecular been elucidated. A potent chemical inhibitor breeding applications have been developed of this enzyme has been developed. in chickpea and pigeon pea. Efforts have Epidemiological studies have shown the been made to deploy marker-assisted back- uniqueness of the strains of M. tuberculosis crossing and marker-assisted recurrent circulating in the Indian subcontinent and selection approaches for enhancing drought could be potentially used to design tolerance in chickpea and molecular intervention strategies to be adopted to mapping of fusarium wilt and sterility combat tuberculosis in the country. mosaic disease in pigeonpea. A total of 182 Indian scientists have been trained in Novel paradigms of inhibitor design molecular breeding of crops.

Work undertaken on inhibitor design against Research on Hepatitis C Virus key metabolite pathways to decimate infectious agents was undertaken at NII, In the work undertaken at IISc., Bangalore, New Delhi. Investigations led to ICGEB, New Delhi, UDSC, New Delhi, identification of some hits to tackle bacterial, ACTREC, Navi Mumbai and Center for mycobacterial and malarial affliction. Liver Research & Diagnostics, Hyderabad Characterization of novel molecular bioactive compound from Phyllanthus mechanisms involved in biosynthesis of amarus plant has been found to efficiently mycobacterial virulent lipids in M. inhibit Hepatitis-C Virus (HCV)-NS3 tuberculosis has opened new avenues for protease and block replication of viral drug discovery. The role of carbohydrates RNA without showing cytotoxicity. A in biological activity of the glycopeptidyl molecular switch for translational to

50 Annual Report : 2011-12 Biotechnology Facilities, Technology Plateforms and Research Resources replication of HCV RNA which was Nus A and the H-NS family of proteins in successfully targeted with a small peptide E. coli. to inhibit HCV RNA replication has also been identified. High-throughput approaches

Genome Science and Predictive To understand molecular basis of heterosis Medicine in rice, work undertaken at UDSC, New Delhi in collaboration with Maharashtra Hybrid In a network project implemented by UDSC, Seeds Company Ltd., Jalna on transcriptomic New Delhi, NII, New Delhi, University of analysis in rice. A set of seven genes has Delhi, Delhi, Indian Agricultural Statistics been short-listed for validation of gene / Research Institute, New Delhi, AIIMS, New promoter function by transgenic approach. Delhi, Dayanand Medical College, Ludhiana About 25 transgenic events have been and Sri Venkateshwara College, New Delhi, obtained from two genes and the plants are new genes / loci for rheumatoid arthritis being analyzed for functional aberrancies. (RA) and ulcerative colitis (UC) have been Nine more genes have been selected for identified after Genome Wide Association making over-expression and RNAi constructs. Studies (GWAS) carried out on 1500 cases Initial cloning of these genes in primary each and 2000 control subjects of North vectors has been completed. Indian origin in two-stage study design namely discovery phase and replication Genome Mapping and Molecular phase. Differential contribution of multiple Breeding genes, their epistatic interactions and the role of metabolic networks in these two Four mapping populations from crosses inflammatory disorders is the current focus involving parents contrasting for variable of the centre. amount of oil content of Brassica juncea have been developed at UDSC New Delhi. Meta Microbial Biology Research analysis has identified one consensus QTL in a confidence interval of 2.4cM between Work undertaken on Microbial Biology 32.5 to 35.9 Cm. Molecular maps of three aspects at CDFD and CCMB, Hyderabad populations have been developed and these led to delineation of a spectrum of maps have been further saturated with more transcription termination efficiency number of microsatellite and other PCR generated by perturbations of Rho, Nus G, based markers.

51 Biotechnology Facilities, Technology Annual Report : 2011-12 Plateforms and Research Resources

Computational and System Biology in mouse models of depression and related Research disorders are in progress.

A database of aligned protein domain Programme Support superfamilies, the superfamily alignment database update has been developed by Programme Support is given to an NCBS, Bangalore and IISc., Bangalore. A identified institution / department (either computational pipeline, Pocket Annotate has as single institutional or multi-institutional been developed to identify potential ligand- programme) with multiple investigators in binding sites by comparing pockets in a various disciplines to create and strengthen protein with a library of well-known ligand research capabilities at university or binding pockets, given the three- institutional level for categorical research dimensional structure of a protein. A for different disciplines through joint genome wise dsRNA screen for genes research effort to focus on common research involved in endocytosis using a new problems. The mode of support contributes methodology for screening of perturbation towards enhancing the core competence of has been completed. the institution/department in biotechnology research. Epigenetic Research The salient achievements of the ongoing Genome of Indian isolate of Hydra activities are: vulgaris has been sequenced and also its transcriptome has been characterized for the Bioreactors for tissue engineering of first time at IISER, Pune, CCMB, Hyderabad, liver and cartilage tissue engineering ARI, Pune, CDFD, Hyderabad and TIFR, have been developed and validated at Mumbai. A database of histones and Sree Chitra Tirunal Institute of Medical their modification and modifiers has also Sciences, Trivandrum. An electrospinning been developed and made freely available facility has been set up for the fabrication online. The state-of-the-art breeding of polymer nanofibers for various and transgenesis facilities for Hydra tissue engineering applications. New and Zebrafish have been created. High- biometerials such as polymers, honey- throughput studies for under-standing comb structured polymer membranes genome-wide epigenetic patterns using bioceramics and components have been neural stem cells / neural progenitor cells prepared.

52 Annual Report : 2011-12 Biotechnology Facilities, Technology Plateforms and Research Resources

Real-Time PCR based diagnostic tests have A cryopreservation protocol has been been developed for non-invasive pre-natal established for prevention of Mononuclear diagnosis of β-thalassemia using cell free Cells (MNCs). fetal DNA in maternal plasma with an overall sensitivity of 83% and specificity of New techniques for In-gel detection of 71% at AIIMS, New Delhi. Out of 120 Steroid proteins, purification of novel enzymes and Resistant Nephrotic Syndrome (SRNS) characterization of biofilm formation by force patients, homozygous and compound spectroscopy have been developed jointly at heterozygous mutations were seen in 8 Anna University, Chennai and Madurai patients while single heterozygous variants Kamraj University, Madurai. Patents have were found in another eight patients. been filed for new electrophoretic technique, for production of novel media, process for An antigen detection kit using monoclonal protein purification and for bacterial cell antibodies against filarial candidate antigen imaging. SxP for field based diagnosis of filariasis has been developed at Anna University, Sixty-one SNPs have been genotyped in 500 Chennai. A more sensitive, reazurin-based coronary artery disease (CAD) patients with fluorimetric method has been developed for a strong family history of cardiovascular detection of Shigella. disease and 500 asymptomatic controls enrolled from the community at Thrombosis A serum-based biomarker for stroke has Research Centre, Bangalore. Eleven SNPs been identified through large-scale have shown significant association with proteomics study carried out jointly at CAD. Institute of Bioinformatics, Bangalore and NIMHANS, Bangalore. The biomarker has A hybrid cytosine deaminase / uracil been validated using ELISA on a larger phosphoribosyl transferase, a suicide gene patients cohort. Clinical utility of this therapy system to induce cell death through biomarker is being investigated. apoptosis has been established at IIT, Guwahati. A chitosan based nanocomposite Chitosan / Wollastonite, chitosan / b-TCP has been developed for cellular delivery of and PVA / TiO2 3D scaffolds and silk proteins and nucleic acids. nanofibres for bone and cartilage tissue regeneration have been developed at Pilot microarray studies utilizing human National Institute of Technology, Rourkela. subcutaneous and visceral fat biopsies

53 Biotechnology Facilities, Technology Annual Report : 2011-12 Plateforms and Research Resources revealed differentially expressed genes and rice has also been developed by RNAi their functional defects in patients with Type mediated silencing of mips and ipk1 genes. 2 diabetes at Madras Diabetic Research Molecular and biochemical analysis of T2 Foundation, Chennai. transgenics are in progress for selecting rice with reduced level of phytic acid. FTIR imaging method has been developed for early and rapid diagnosis of drug T-3 progenics of leaf hopper resistant Allium induced liver injury at IISc., Bangalore. The sativum leaf lection (ASAL) expressing IR-64 method is more rapid and sensitive as rice plants have been established at Bose compared to biochemical assays used to Institute, Kolkata. A full-length candidate diagnose liver damage. Method will be mungbeen yellow mosaic India virus further validated with clinical samples. resistant gene (MYMIV-R) has been isolated and characterized from Vigna mungo. A A human BAC library from the DNA of reference proteome map of MYMIV resistant an ethnic Indian male (IMBL4) of normal V. mungo has been generated and 109 karyotype covering the haploid human identified proteins have been registered in genome more than three times has been PRIDE database. constructed at Manipal University, Manipal. IMBL4 BAC library represents Co-expression of transcription factors cloned the first catalogued Indian genome from Eleucine corocona enhanced drought resource for applications in basic and tolerance in rice at UAS, Bangalore. A few clinical research. markers associated with root, water use efficiency (WUE) and yield in rice have been A miRNA expression signature that can identified. These have been used for predict glioblastoma patient survival has marker-assisted selection to introgress traits been identified at IISc., Bangalore. This into an elite variety of rice. Introgressed finding may be useful in development of line KMP-175 of rice with superior adoption targeted therapy and selection of high risk for aerobic cultivation has been transferred cancer patients for adjuvant therapy. for multi-locational trials to the rice breeding unit at Mandya, Karnataka. An agreement Transgenic high iron Indica rice has been has been signed with M/s Ankur Seeds to developed using rice ferritin gene driven by introgress the markers identified in rice by endosperm specific glutelin promoter at initiating a focused marker-assisted selection University of Calcutta, Kolkata. Low phytase programme.

54 Annual Report : 2011-12 Biotechnology Facilities, Technology Plateforms and Research Resources

Several genes associated with pathogenesis Long Term R&D Projects of Magnaporthe oryzae – blast fungus in rice were identified at MS University of Baroda, Long-term R&D support was provided to Vadodara. individual investigators of high scientific caliber with publications and / or patents Biotech Facilities and Research record at the highest level in recognition of Resources investigators for their recent performance and future work plan. The salient The department has made a tremendous achievements of long-term R&D projects progress in establishing and creating the supported so far under this category are research related infrastructural facilities in summarized below: several Universities/ Institutions. Various A drug combination of curcumin and areas supported are animal house, gene arteether was found to prevent banks, repositories for microbes, plants, recrudescence completely in Plasmodium model organisms and infectious organisms, berghei (ANKA) infected mice model at IISc., centres for genetic engineering etc. at Bangalore. The combination has potential different institutes and universities across to prevent recrudescence in falciparum the country. Along with these facilities, new malaria and relapse in vivax malaria. facilities in the form of NMR, fMRI, green houses, phytotrons, DNA sequencing A new pathway for the aggregation of the facilities for x-ray crystallography, molecular prion protein has been discovered at NCBS, modelling and microarrarys were also Bangalore. Aggregation of the prion protein established. The main research highlights leading to the formation of amyloid fibrils of the support are follows – is a characteristic feature of prion-related neurodegenerative disorders. DBT supported ‘Primate Resource and Research Center and Facility on Small Protein-protein interactions with RNA Animals, an incubator for translational polymerase core enzyme lead to its reduced research’ has been established at NII, New susceptibility to rifampiain used for active Delhi. The R&D work at the facility leads tuberculosis at IISc., Bangalore. A novel to the identification of full length promoter RNA polymerase-binding protein of buffalo beta-casein gene from buffalo discovered could mitigate the effect of genome and new process of amplifying a rifampiain on RNA polymerase activity. long length of amplicon (long PCR) from

55 Biotechnology Facilities, Technology Annual Report : 2011-12 Plateforms and Research Resources

genomic DNA of Indian River Buffalo. The potent antimalarial and in combination promoter is cloned, sequenced and with Artimisinin, prevents parasite characterized in terms of its activity. The recrudescence in mice. Efforts are being procedure will provide the basis for cloning made to generate recombinant the desired gene of therapeutic interest gonadotropins for therapeutic purpose. under the buffalo beta-casein promoter for These include production of host strains creating the transgenic buffalo(s). capabale of producing glycoproteins with human like glycan moieties by At ‘National Repository for Filarial Parasites glycoengineering the host organisms. & Reagents, “Sevagram Maharashtra”, a Expression profile chaperone proteins of SXP/RAL2 family protein WbL2 is identified Plasmodium falciparum in malaria protein as diagnostically important candidate with was shown to correlate with distinct 100% sensitivity and 90% specificity for physiological states of the parasite. Heat detection of filarial infection. Filarial shock protein 90 form P. falciparum and derived recombinant proteins viz., BmALT- T. evansi were shown to be suitable drug 2, BmCys and WbL2 suppressed the targets against protozoan infections. Also immunopathologies associated with diseases an inhibitor was recognized as a candidate progression, induced anti-inflammatory drug. effect and showed therapeutic potential in rodent model of autoimmune diseases viz., A new algorithm ‘PocketAlign’ is available Type-I diabetes, rheumatoid arthritis and as a web service at http:// colitis. The filarial serum bank has a proline.physics.iisc.ernet.in/pocketalign/ for collection of more than 500 bancroftian structural superposition of binding sites. filarial sera of different patients groups of Similarly, a new classifier incorporating ten different endemic zones. features at the protein-protein interface was developed to further improve the DBT provided infrastructure support for discrimination between biological and non- Basic Biology Research at IISc, Bangalore. biological contacts at the protein interface. As a result of the support, IISc has The work helped the international performed research in many directions community to bridge the gap in the under the major heads of ‘Pathogen automated availability of true quaternary biology, Biological Signalling Mechanisms structures from the PDB for all affinities and Biomolecular Architecture and and the method is freely available at http:/ Interactions’. Curcumin was shown to be a /pallab.serc/iisc.ernet.in/IPAC/.

56 Annual Report : 2011-12 Biotechnology Facilities, Technology Plateforms and Research Resources

For the first time, it has been shown that Of these 30 datasets were meant for ab-initio the volatile signals produced by fruit can SAD/MAD phasing. Till now, 28 show diel differences based on the activity international publications came out as part period of the dispersal agent. Similarly, an of this project. experimental system for successful differentiation of in-house derived Boost to University pluripotent stem cells viz. ES-cells and iPS- Interdisciplinary Life science cells to cardiac lineage is developed and Departments for Education & molecular and epigenetic regulation of its Research (BUILDER) Scheme differentiation is studied. The BRIT1 (BRCT- repat inhibitor of hTER expression 1) is During the 11th five year plan, the shown as inhibitor of cell proliferation i.e. department launched a scheme i.e. DBT- having anti-proliferative activity. Boost to University Interdisciplinary Departments of Life Sciences for Education During the 11 plan, the institute has trained and Research (DBT-BUILDER) for advanced 90 Ph.D. students and 209 numbers of education and research for the upgradation/ students are undergoing training for Ph.D. reengineering/remodeling/ creation of Life The institute published about 400 Science departments in central and state publications under the programme support. universities. From 2007 onwards almost 14 universities have been supported so far A DBT-BM14 program coordination unit under the aegis of this scheme. (DBT-BM14-PCU) has been established at NII, New Delhi with an objective to acquire During the last financial year, 11 universities and maintain synchrotron X-ray beam line viz. Madurai Kamraj University, Madurai; (BM14) in partnership with MRC, EMBL and University of Calcutta, Kolkata; The M.S. ESRF to enrich biomedical research University of Baroda, Vadodara; Pondicherry by providing access to the synchrotron University, Pondicherry; Karnataka beam line to the macromolecular University, Dharwad and University of crystallographers. So far more than 60 Rajasthan, Jaipur; Mahrshi Dayaynand proposals have been processed from University, Rohtak; Shivaji University, different institutions across India. More than Kolhapur; Patna University, Patna; Punjabi 500 crystals were subjected to the University, Patiala; and Barkatullah synchrotron beam exposure and data set University, Bhopal were supported. These were collected for about 200 protein crystals. universities have been provided financial

57 Biotechnology Facilities, Technology Annual Report : 2011-12 Plateforms and Research Resources support in terms of infrastructure; DBT-Calcutta University Interdisci- fellowship; faculty appointment; advanced plinary Life Science Programme for training programmes for faculty, students Advance Research and Education and staffs. This year, after the advertisement, the department received 19 proposals under An innovation program on Symbiotic this programme which were initially Nitrogen Fixation has been initiated. PG labs screened by the Screening Committee have been renovated. Sophisticated instru- Experts and finally four universities viz. ments like ITC isothermal calorimeter, Jawaharlal Nehru University, New Delhi; phosphor and fluorescence imager, atomic Aligarh Muslim University, Aligarh; force microscope and total internal reflection Mahatma Gandhi University, Kottayam; and microscope have been installed. 3 M.Sc. and Guru Ghasidas Vishwavidyalaya, Bilaspur 8 Ph.D. students have been registered and were selected for the further processing. 5 technical staffs have been recruited. Some of the achievements in some of the universities supported so far include: Scientific progress

DBT-Madurai Kamaraj University Group-1: Biomedical Science Centre of Life Sciences for Advanced Research and Education; Madurai Molecular mechanism of diseases: Under the Kamraj University, Madurai Pathophysiology and molecular mechanisms of cigarette smoke-induced degenerative Introduction of 5 year integrated M.Sc - Ph.D diseases study, a major long-lived radical programme in Genomics Sciences in the from cigarette smoke was isolated and School of Biological Sciences, Madurai characterized as p-benzosemi-quinone which Kamaraj University. 21 students have been is responsible for cigarette smoke-induced selected and the course commenced. degenerative diseases. Teaching, technical and supporting staff positions were appointed following the Biomarkers: In order to identify diagnostic University rules and regulations. The markers in diabetes mellitus associated renovation work in the laboratory facility, cardio-vascular disease, the participating computer lab facility, sophisticated group studied the effect of oral instrument rooms etc. was completed and hypoglycemic agent metformin on the status the first batch students and staff are using of some important oxidative stress markers these facility. viz. ROS, AOPP and pentosidine.

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Drug-development and nano-based drug degradation ability had been isolated from delivery: Chandipura virus (CHPV) has soil rich in recalcitrant materials that can recently been classified as an emerging efficiently degrade PES and use it as sole human pathogen in the Indian sub- carbon source for survival. continent. Recent work focused on the development of effective peptidomimetic Industrially important enzymes: Cellulose approaches towards the inhibition of viral and Xylanase producing Penicillium citrinum replication cycle of CHPV in culture cells. and Simplicillium obclavatum bacterium from soil has been isolated. Group-2: Pathogenic host-microbe interaction DBT-Centre for Cellular and Molecular Biology, University of Baroda Fungal infection by Macrophomina phaseolina Interdisciplinary Life Science severely affects the production of jute. They Programme for Advance Research and have identified and isolated the Education, Vadodara differentially expressed transcripts induced upon Macrophomina phaseolina infection in The foundation of Central Building named jute by differential display analysis. as Vikram Sarabhai Science Block, is laid and construction has started. Sophisticated Under phyto-remediation study, twelve instruments like FACS, Confocal endophytes were isolated from surface microscope, fluorescent microscope and sterilized Typha angustifolia plants collected ultracentrifuge have been installed in a from the uranium mines of jaduguda. temporary facility and are being used by the research scholars of the University. Group-3: Microbial ecology Efforts are initiated to start a five year integrated programme in Cellular and Microbial-diversity: In order to understand Molecular Biology by academic year 2012 the vast microbial diversity of Sunderban, in collaboration with NCBS-TIFR, a large-scale metagenomics study has been Bangalore, TIFR, Mumbai and visiting carried out on both water and soil samples faculties. Faculty level syllabus Committee collected from Jharkhali area. has been constituted.

Bioremediation: A new Pseudomonas In order to use stem cells as therapeutics, strain having Polyethylene succinate (PES)- an interesting aspect has been worked out

59 Biotechnology Facilities, Technology Annual Report : 2011-12 Plateforms and Research Resources under the project micro RNA profiling of in lineage differentiation and homing cord blood derived mesenchyme stem cells potential. (MSCs) and differentiated cells and its role

Fig.3.1: Stem cell differentiation and islet neogenesis

❖ ❖ ❖

60 Chapter 4

RESEARCH AND DEVELOPMENT

Support to research and development in salinity and/or drought stress-induced different sectors is a major activity of the helicase from rice and its functional Department. While potential investigators validation is being carried out at ICGEB, routinely submit R&D proposals to the New Delhi. Stress-responsive helicase Department for funding, projects are also (1.3 kb) called BATI helicase from rice has generated in priority areas through brain been cloned and found to be up regulated storming sessions and expert consultations in response to salinity and cold stresses. held under the aegis of various task forces The expression and purification of the BATI and other expert committees. The protein is in progress. Department has launched a new online project submission and monitoring system In another project of basic nature, (e-ProMIS) and has adopted a new suppression of innate immune response of competitive research grant process. The rice by bacterial effector proteins has been projects are funded for basic and applied studied at CCMB, Hyderabad. Xanthomonas research for cloning and characterizing genes orzae pv. Oryzae (Xoo) uses a type 3 secretion of importance, promoters, QTLs, developing system (T3S) to suppress rice innate immune enabling technologies, value added bio-mass responses. Using Agro-bacterium mediated and products from natural resources and transient transfection assays, it was shown processes for improving productivity, that the XopN (Xanthomonas outer protein healthcare, remedies for environmental N) protein suppresses the rice immune problems and industrial production. responses like, innate immune response associated programmed cell death (PCD) Agricultural Biotechnology reactions; innate immune response associated callose deposition in rice leaves Crops that is induced by Xoo LipA or a T3S Xoo mutant; resistance against Xoo infection that Rice is induced by prior treatment with T3S mutant of Xoo. The group has cloned genes Molecular cloning and characterization of for 15 other T3S secreted proteins of Xoo

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into Agrobacterial vectors and introduced production and TGMS multiplication. These them into plant cells via transfer. promising TGMS lines will be utilized for two line hybrid development programme. In a project for enhanced nutritional content at UAS, Bangalore, nearly 100 segregants Wheat showing high protein content (12-15%) that were identified in the F6 population were In a project on improvement of biscuit analyzed for lysine and methionine content making quality of Indian wheat, studies were and cooking quality/nutritional parameters. undertaken on genotype utilizing soft wheat Several promising inbreds with preferred germplasm lines including Indian land race plant type and enhanced nutrition and good of wheat, Nap Hal, and synthetic hexaploids. grain quality have been identified with Nap Hal, a unique Indian land race of wheat, medium to early duration. These promising was identified for possessing both weak inbred are being evaluated in multiple gluten and soft grain characteristics. Weak environments and under contrasting gluten is caused by double null trait at Glu- moisture regimes. Also high protein inbred Di locus where both the subunits of HMW lines for drought, aerobic and puddled glutenins coded by the locus are absent. conditions were identified. Several high Double null trait Glu-DI locus has been protein introgression lines in popular transferred into high yielding backgrounds background are being developed through using molecular approach for improving marker assisted backcrossing using MAS. biscuit making quality of Indian wheat.

For developing two line hybrids in rice In another project, identification and (Oryze sativa L.) good results were obtained characterization of differentially expressed at TNAU, Coimbatore. Thirty suspected genes during heat stress in wheat has been TGMS lines were identified for TGMS undertaken at UDSC, New Delhi. Some of sterility under high temperature regime and the heat stress-related ESTs chosen for a reversion to fertility under low temperature detailed characterization are the TaHSF, regime. Eight promising TGMS lines viz., TaHSP26, TaMIPS2 and a TaMP. Real time TS0912, TS0914, TS0915, TS0917, TS0924, analysis found HSF to be induced by TS0925, TS0926 and TS0928 were calcium, salt ABA, PEG and heat stress, characterized for CST/CFT, sterile and fertile particularly in various flower and seed phase, critical stages of thermo tissues. Arabidopsis T4 lines over expressing sensitiveness, safe period for hybrid seed these ESTS are being characterized.

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Maize resistance against three isolates Sg384, Sg445 and Sg561 representing three locations In a project on molecular characterization Barmer, Rajasthan, Banaskantha, Gujarat and and introgression of QPM for maize quality IARI, New Delhi respectively. Resistant improvement through marker assisted and susceptible lines were selected for selection, the non-QPM inbred lines are crossing to generate mapping populations being converted into QPM version. Recovery segregating for isolate-specific DM of homozygous plants carrying o2 locus has resistance. been achieved. These lines are now being fixed for the o2 allele before using them for Ragi generation of QPM hybrids. Isolation and validation of salt tolerant Sorghum genes in Ragi (Eleusine coracana L.) is being carried out at TNAU, Coimbatore. Extreme Study is being carried out at NRCS, rice and ragi genotypes exhibiting Hyderabad towards establishing the role of contrasting level of salinity tolerance have volatile cues in oviposition preference of been identified. Physiological studies sorghum shoot fly, and identifying revealed the superiority of Trichy 1 ragi in associated QTLs. The role of volatiles and terms of salinity tolerance. Protein profiling epiculture waxes in oviposition behavior of has resulted in the identification of key shoot fly on sorghum plants has been protein exhibiting contrasting behavior in identified. Further the volatile compounds the extreme ragi genotypes. Rice homologs were identified in the shoot fly susceptible of putative candidate genes controlling parent 296B and susceptible RILs. In salinity tolerance have been isolated and addition to the pronounced quantitative cloned. variation, substantial qualitative variation was also noticed among the parents. Plant Molecular Biology Programme

Pearl Millet Stress-associated proteins (SAPs) that interact with self and kinase in different sub-cellular In a study towards generation of mapping locations, viz OsSAP11 and OsRLCK253 have populations and identification of QTL(s) for been identified. These have been shown to Downy Mildew Resistance in Pearl Millet, confer stress tolerance on transgenic rice lines were screened for downy mildew seedlings. Two stress-responsive promoters

63 Research and Development Annual Report : 2011-12

have been characterized in transgenic rice. (>300x) and for 2AL about 50,000Mb (96x) CRY1 over-expression regulates plant height sequence is already generated. As many as by altering the expression of gene involved 264,555 contigs for 2AS and 321,517 for 2AL in GA metabolism, auxin signaling and have been generated. N50 values for 2AS transport and cell wall modification. The and 2AL assemblies are 2398bp and 2688bp, response regulator, OsRR6, a component of respectively. As many as 1908 genes have two-component sensor regulator system, been predicted form 2AS and 2872 genes functions to intergrate hormone, light and from 2AL. Using this data more than 6000 stress signaling pathways, as revealed by SSR markers have been identified, which over-expression in Arabidopsis. Full length are now being validated. Further, sequencing cDNAs of five TaSERKs from wheat have of 4608 BAC clones has been completed been cloned for functional analysis. Doubled from both the ends and nearly 46,00,000 bp haploid transgenic of wheat over-expressing of wheat genomic sequence has been HVA1 gene conferring drought tolerance generated. An average read length of ~500 with faster seed germination and seedling bp per BAC end has been achieved. The establishment have been identified. Rice BAC end sequences were searched for any ClpB/Hsp100-cyt protein gene family has significant homology in the assembled EST been characterized. database. As many as 3702 BAC ends find homology in the clustered-ESTs and 96 BAC Network Programmes ends showed positive hits with the protein database Uniprot-Swissprot. Physical Mapping and Sample Sequencing of Wheat Chromosome 2A Functional analysis of gene regulatory networks during flower and seed BAC libraries were developed from flow development in rice sorted chromosomes of Chinese Spring double ditelocentric stocks (2n = 42 While working towards delineation of gene +2ASt’’+2Alt’’) in collaboration with Institute regulatory network leading to reproductive of Experimental Botany, Czech Republic. development in rice, substantial progress Both short arm and the long arm of has been made towards characterization of chromosome 2A have been sequenced using key components and their down- and up- two NextGen sequencing platforms Illumina stream interactors. For floral transition and and Roche 454, in collaboration with TGAC, early flowering events, orthologs of various Norwich, UK. For 2AS, about 131, 603Mb components of Arabidopsis photoperiod,

64 Annual Report : 2011-12 Research and Development

vernalization, GA and autonomous O. nivara: 166-30 with dense panicle and pathways have been identified from rice with 166-2-1 with lax panicle of Swarna x O. the eventual aim to decipher unique nivara) at 5 locations was in top 5 of 16 components, if any, involved in regulating entries and was promoted to Advanced flowering in a dicot and monocot species Variety Trial 2-IM 2011. and that too with contrasting photoperiodic sensitivity. Four promoter elements, Pan3- At NRCPB, IARI, New Delhi, a major effect CRP, PP12, M2 and RP6, have been QTL for grain number qGN4-1 on the long validated for their expression in arm of chromosome 4 localised with flanking reproductive tissue-specific. Pathway markers HvSSR04-41 and HvSSR 04-46 is analysis of differentially expressed genes targeted for fine mapping, identification of has implicated hormone biosynthesis candidate genes and functional validation. pathways as major regulators of early seed The full length GN4-1 gene is being cloned development. The marker-free, transgene- and mobilised into pCAMBIA vector for stacked rice plants for two traits (Chitinase possible trasformation of rice lines. and Osmotin genes) were generated by sequential retransformation. These plants At PAU, Ludhiana, Xa30(t) gene identified displayed more than 60% resistance to the from Oryza nivara and transferred to O. sativa sheath blight disease caused by Rhizoctonia L has now been redesignated as Xa38. This solani. A pMVIGS system has been used to gene has been mapped based on sequence carry out virus induced silence the rice gene information and gene specific markers have phytoene deaturase. been developed for use in MAS. Two more BB resistance genes, xa-g from O. glaberrima Identification and functional analysis of and xa-b from O. barthii have been mapped genes related to yield and biotic stresses on chromosome 6S and linked markers developed for use in MAS. Inheritance of At DRR, Hyderabad fine mapping and bacterial blight resistance in an accession introgression of yield QTLs from wild (100098) of O. rufipogan is being studied here. species is being pursued. Yield QTL yld2.1 from O. rufipogan has been introgressed into At NRCPB, blast resistance studies were a parental line KMR3 for fine mapping this perused in TP-Pi54 rice transgenic plant. QTL. In another study on mapping of dense After inoculation with the blast spores Pi54 panicle trait is being followed using two gene expression was found higher in introgression lines derived from Swarna X transgenic Pi54 plants. At DRR, Hyderabad,

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two or three of the blast resistance genes tolerance, fine mapping of genes and allele Pi1, Pi2 & Pi54 have been introgressed in mining for DREB1, Hd3a and PTF1 genes the background of BPT5204 and Swarna. by TILLING has been done. DUS characterization of 89 mutants, phenotypic In area of gall midge resistance, at DRR, evaluation of 295 mutants contributed by Hyderabad, two of the gall midge resistance different centers has been done. Gm8 and Gm4 conferring wide spectrum of resistance have been mapped. They are now Puccinia triticina - Genomics Network being fine mapped, clone and validated for their function in collaboration with ICGEB, The sequencing of Puccinia triticina was done New Delhi. using 454 GS FLX sequencers. Assembled large contigs represented 102 MB of genome. At DRR, Hyderabad, brown plant hopper Assembled data consists of 12984 large resistance studies in two mapping contigs and 2301 scaffolds. A total of 24005 populations showed that resistance for the genes were predicted out of which 17528 trait polygenic. genes were protein coding while 3114 genes were TE related. A total of 16373 SSRs were Generation, Characterization and use of found in the genome which includes 64% EMS induced mutants of upland variety of mono-nucleotide. Nagina -22 for functional genomics in rice In another experiment, behavior of select During this period, a total of 507 selected pathotypes was observed on Near Isogenic mutants have been grown in the mutant lines or lines with known resistance genes garden and all these have been described at two temperature regimes. Some of the by distinctness, uniformity and stability resistance genes have shown effect of (DUS) parameters. These data along with temperature on the expression of host other valuable information including DNA pathogen interactions. At TNAU Centre, the fingerprints have been entered in the Rice rust reaction of the lines carrying leaf rust Mutant Database. About 4120 mutagenised resistance genes Lr24 and Lr9 has been lines have been maintained at NRCPB, New studied. Three wheat genetic stocks Delhi. Characterization of 15 lines for including one leaf rust susceptible (PBW226) drought tolerance, gene expression profiling and their resistant NILs (HW 2016+Lr24 & using microarrays to identify genes for seed HW2057+Lr9) were used for comparative size, plant architecture, and drought transcript profiling.

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Generation of salt-tolerant rice plants: A cultivars, landraces, wild species etc. have been translational approach screened for grain Fe, Zn and yellow pigments (in durum). Accessions/lines having grain Fe At Bose institute, Kolkata; advancement of and Zn concentrations two to three folds higher the earlier transgenic plants harboring than in the modern wheat cultivars identified. PcINO1 (both in PB1 and IR64 var.) have At IARI, New Delhi, synthetic derivatives and been done upto T4 stage and molecular and T. spelta accessions have been used in physiological characterization carried out collaboration with HarvestPlus. At IIT, Roorkee, following identification of salt-tolerant lines. the non-progenitor genomes carrying accessions From growth pattern in presence of salt and of Ae Kotschyii, Ae. peregrine and Ae longissima the photosynthetic efficiency analysis it was etc., have been used as donor sources while found that the transgenics were salt-tolerant PAU have primarily used T. monococcum and and photosynthetically as efficient as the T dicoccoides as a high zinc and iron source to control plants, sometimes more efficient than develop introgression and addition lines. The the control. work in Phase I also highlighted that the chromosomes 2 and 7 harbor genes/segments Identification of candidate genes for for higher iron and zinc concentration and enhanced water use efficiency in rice phytosiderophores. Five different QTLs linked through activation tagging to yellow pigment were identified on chromosome 1A, 3B, 5B, 7A and 7B in durum. Transformation work was initiated in all the four network centres viz., HCU, Osmania Rice Bio-fortification with Enhanced Iron University, DRR and ANGRAU, with the and Zinc in high yielding non-basmati variety BPT5204 with the gene pSQ5. cultivars through marker assisted breeding Confirmation studies for these transgenics and transgenic approaches are underway. Procedures for precise estimation of iron and Crop Bio-fortification zinc concentration in grains were standardized using Atomic Absorption Biofortification of wheat for micronutrients Spectrometer and 2, 2-dipyridylyl agent. through conventional and molecular Necessary infrastructure facilities have been approaches created for accurate screening of micronutrients. More than 3500 rice A large number of germplasm lines including accessions including ~252 rice landraces of

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CG collection known for high grain nutritive expression in oil bodies) were characterized value, ~100 popular rice cultivars and ~650 at the molecular level to study the advanced breeding lines developed through introduction, expression and stable various breeding populations has been transmission of the transgenes. Inheritance screened. Low genetic variations for grain studies indicated a Mendelian segregation Fe levels were observed compare to that of in most of the transgenic events. The grain Zn contents. About 14 genotypes have selected positive transgenic events were been identified with high Zn content in advanced to T2 generations for biochemical polished grains ranging from 26ppm to analysis. These events were characterized 32ppm. based on their carotenoid profiles, several of which showed a multi-fold increase in Development of micronutrient enriched the levels of β-carotene when compared to maize through molecular breeding untransformed control (1.2 to 5.4 μg/g).

Extensive evaluation of maize genotypes Establishment of screening facility for iron indicated the availability of large variation and zinc bioavailability for kernel Fe and Zn concentration in maize. The promising inbreds thus identified have A state-of-the art facility for screening iron, great potential as donor in the breeding zinc and β-carotene bioavailability using programme. Research efforts presently under simulated in vitro digestion/Caco-2 cell progress to identify QTLs for kernel Fe and model have been developed in NIN. The Zn would further help in expediting the facility is now ready for taking up screening enhancement of micronutrient concentration. of micronutrient bioavailability from bio The project is thus expected to result in the fortified rice, wheat and maize for its development of maize inbreds and hybrids selection and breeding. enriched with higher iron and zinc content. Accelerated Crop Improvement Programme Crop biofortification of Groundnut and Pigeonpea Department launched a major translational project on crop improvement where Over 90 primary transgenic events of molecular markers already available in groundnut (var. JL 24) carrying maize public domain for important agronomic phytoene synthase gene (psyI) driven by an traits in wheat, rice, soybean, chickpea and At oleosin promoter (for seed-specific maize have been validated and are being

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introgressed in the high yielding cultivated and chickpea; and 8 QPM hybrids will be in varieties suitable to specific agroclimatic final stage of development. Forty one centres zones and also at all India basis by are participating under this programme. pyramiding genes through Marker Aided Breeding (MAB). The various biotic stress SAUs Programme Support traits being undertaken in wheat are Leaf rust, Strip rust, Stem rust, Brown and Yellow The Department extended programme rust. Varieties of both Triticum (17 varieties) support for R&D in agricultural and Durum wheat (2 varieties) are being biotechnology to four state agricultural targeted and efforts are being made to bring universities. Highlights of their resistance to almost all races of these rust achievements are as follows: prevalent in the country by pyramiding these genes. Similarly quality traits of wheat UAS, Dharwad namely, high grain protein content (HGPC), low amylose content, high gluten strength Three transgenic pigeon pea events carrying and grain hardness in 13 Triticum varieties Cry1Ac gene for pod borer resistance have and HGPC, high yellow pigment content been selected based on repeated insect and lipoxynase activity in two Durum bioassay results and southern hybridization varieties are being brought through MAB. data. Currently these events are being characterized for expression levels of target In rice 14 varieties for traits like Bacterial protein in leaf, flower and tender pods. leaf blight (5 genes), Blast (5 genes), Gall midge (3 genes) and Brown plant hopper (3 Four different genes coding for chitinase 3 genes); 3 varieties for salt resistance (Saltol genes for endoglucanase were cloned from gene), 4 varieties for submergence tolerance Trichoderma and expressed in yeast. Isolates (Sub 1 gene), 5 varieties of chickpea for of B. thruingiensis with 100% toxicity at end resistance against Ascochyta blight (prevalent of 48 hours on Plutella xylostella have been races) and Fusarium wilt (2 races); 5 varieties identified. Mutants of cry1Ac and cry1AcM of soybean for kunitz trypsin inhibitor and have been developed. Two mutants showed rapid conversion of 8 hybrids into Quality enhanced mortality (10 and 20% more than Protein Maize are being developed by original cry1Ac). A more efficient pyramiding genes mentioned above. At the Agrobacterium-mediated transformation time of project completion, about 45 high method to transform tomato cultivars, Pusa yielding varieties of wheat, rice, soyabean Ruby and DMT2 has been developed.

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Transformation of native and codon In pigeonpea, one mapping population each optimized (synthetic) cry1Ac to tomato plants for Fusarium wilt-GS1 x ICPL8863 and SMD- was attempted and the plants are at various ICPL8863 x BSMR 736 were forwarded to F6 stages of development. generation. The subsets of RILs were subjected to SSR markers segregation testing and they In sorghum BC3F3 homozygous Near Isogenic were found to be segregating into expected

Lines (NILs) carrying different combinations 1:1 ratio. Currently the F7 seeds from selfed of charcoal rot (CR) resistant qCR1, qCR2 and individual RIL are being harvested from field. qCR3 QTLs from E36-1 in the background of M35-1 and SPV86 were field evaluated and Maize Ac and Ds transposons were used found to be resistant to the disease. These for generating tagged mutants in M 35-1, a varieties carrying all the three QTLs, together popular rabi genotype of sorghum for its with other combinations are being multiplied functional genomics. One mutagenic plant in the field for station trials and large-scale and one Ds-tagged mutant was obtained field demonstrations. Three stable QTLs for with transiently expressed transposase stay green, one for water use efficiency and system. In addition, 4 plants with ten other drought and yield related traits in transposed Ds containing iAc were obtained. sorghum were also mapped. M35-1, SPV86 and SPV570 were rabi varieties introgressed with these QTLs. The BC3F3 NILs carrying different combination of QTLs are currently (rabi 2011-12) being field evaluated.

A set of 17 advanced breeding lines of Pigeon Pea developed through MAS for resistance to Fusarium wilt and another set of 41 Conformation of homozygosity of QTLs with different combination in BC3F3 progenies in SPV86 background additional progenies selected based on DNA markers (SCAR) linked to recessive allele of a Fusarium wilt resistant gene from F5 generation population derived from various combination of parents were field evaluated and the superior lines will be forwarded to Seed multiplication of CR resistant QTLs further evaluations and selections to include introgressed M35-1 and SPV 86 -rabi-2011-12 into multi location trails. Fig. 4.1

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Fig.4.2: BC2F3 population derived from crosses with Ae. speltoides in the field

PAU, Ludhiana for various traits suited to direct seeding and for yield and yield components. Some As part of effort to develop heat tolerance in high yielding lines have been identified for wheat, a linkage map has been generated from testing in replicated multi-location trials. C306 X PBW534 with SSR markers. Various These RIL populations are being further components of heat tolerance are being analyzed for mapping QTLs associated with mapped onto this linkage map. In addition, yield and yield component traits suited to introgression profiling of T. durum- ae speltoides aerobic conditions. For developing resistance is being done to develop a panel of to stem borer and tolerance to abiotic chromosomal segment substitution lines stresses, ZAT12 and Cry1Ac genes have been (CSSL) of ae. speltoides in T. durum background. introduced into maize inbred LM5 and LM13, respectively, through particle bombardment In rice to enhance water use efficiency, the using immature embryos and confirmed generated RIL population has been evaluated through PCR.

Fig.4.3 : Transgenics of maize confirmed through PCR

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The glyoxalase gene (Gly I) to induce In rice a QTL near RM8085 on chromosome salinity tolerance is being used for rough 1 linked to grain yield under drought stress lemon transformation. Protocols have been explaining 11.8, 14.7 and 20.9 per cent developed for direct regeneration of plants phenotypic variation in 3 different trials has from cultured epicotyl segments and factors been identified. Preliminary QTL analysis affecting success of biolistics based in cotton led to identify several QTLs transformation have been standardized. including two major QTLs on chromosome 19 and 25 for fiber quality traits across the TNAU, Coimbatore mapping populations and genetic backgrounds. In rice, NILs introgressed with A reproducible genetic transformation QTLs associated with root traits have been protocol has been standardized for hill developed, and also identified proteins co- Banana ecotype ‘Virupakshi’ and 25 putative segregating with root penetration ability transgenic hill banana plant lines have been have been identified. Drought tolerant rice developed exhibiting resistance against lines developed through MAS are under Banana Bunchy Top Virus (BBTV), which evaluation. are being maintained in the transgenic green house. An interspecific mapping population Low Phytate maize inbreds are in the was developed between mung bean (Vigna advanced stage of backcrossing. In addition, radiate Wilzck) and rice bean (V. umbellata) transformation protocol for tropical maize and an introgression line VGG RU 1 was has been standardized and gene encoding identified to exhibit complete resistance for Phytase is being used for developing against MYMV. transgenic maize lines.

Transgenic hill banana plants maintained in net house Fig. 4.4

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GBPUAT, Pantnagar calmodulin ‘CaM’ was isolated from finger millet that highly expresses during the grain Under the programme, utilizing Arabidopsis filling stages suggesting that it might be thaliana as model plant, it was observed that involved in the activation of CaM dependant MAPK 3 plays a role of prime importance calcium ATPase transporter that pumps the during Alternaria pathogenesis process. It’s calcium during grain filling. full length gene was isolated and cloned from Brassica for development of knockout In silico experiments identified a key as well as over expression in Brassica. In antioxidant enzyme, namely apx1, that has rice, unique markers associated with salt further been characterized and fully length tolerance were identified which can be used gene isolated and cloned. One novel for breeding salt tolerance. In order to drought inducible gene ‘IDIP’ (Important identify genes for blast resistance, four lines Drought Inducible Protein) has also been showing blast resistance were selected as donor identified. parents and crossed with traditional varieties. Chi-square analysis of the segregation data Network project on development and showed that a major dominant gene was evaluation of salt and drought tolerant conferring resistance to blast and was transgenic rice segregating in a Mendelian fashion. This project is aimed at the development of A full-length gene sequence of a class of salt and drought tolerant “marker-free” rice. calcium sensor in plants known as For this, fusion gene containing both

Fig. 4.5 : Molecular cloning of full length Calmodulin ‘CaM’ gene from Finger millet

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trehalose-6-phosphate synthase (TPS) and tolerance towards salinity and sodic stress trehalose-6-phosphate phosphatase (TPP) in transgenic IR64 rice. Screening of these together was over expressed in a salt lines for the next two generations under sensitive rice variety, IR64 at ICGEB, New normal, saline and sodic conditions at CSSRI, Delhi and DRR, Hyderabad. Four Karnal, revealed that some of these lines independent transgenic events that were are promising in terms of early vigour, southern positive and showed enhanced salt spikelet fertility and overall yield than the tolerance were transferred to the Central Soil control non-transformed IR64 and the best Salinity Research Institute (CSSRI), Karnal local check for salinity and sodicity. for further testing under saline and sodic soil conditions. Preliminary observations The investigators are now seeking RCGM suggested that overexpression of trehalose permission to conduct strip trials of these biosynthesis genes confers enhanced transgenic lines.

WT Transgenic (SL1) Transgenic (SL2) Control Drought Control Drought Control Drought 15 d after stress 30 d after stress 7 d after re-watering

Fig.4.6 : Evaluation of drought stress tolerance of TPSP transgenic IR64 rice vs WT IR64 rice at the vegetative stage carried out at ICGEB, New Delhi.

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DBT-IRRI Project chickpea ICC4958 is being sequenced. The SOLiD platform was used for sequencing From QTL to Variety: Marker Assisted of ICC4958 as well as the wild variety Breeding of abiotic stress tolerant Rice C.reticulatum PI489777 (parent of the varieties with major QTLs for drought, mapping population) and used to identify submergence and salt tolerance unique SNPs. About 4000 SNPs have been selected and are being genotyped for The project has been initiated for transferring generating a high density linkage map of major genes/QTLs for drought, sub- chickpea. Additionally, 2000 SSR markers mergence and salt tolerance into popular polymorphic between the parents have also Indian rice varieties through marker-assisted been identified for mapping. backcross breeding (MABB). The network Simultaneously, deep sequencing of the involves fifteen Indian institutions, including chickpea transcriptome has been done ICAR Institutes, State Agricultural using both the short and long read NGS Universities and Central Universities with platforms and assembled into 34,760 NRCPB, New Delhi being the lead centre. tentative consensus (TC) transcripts The main objectives of the project are: (i) representing 35.5 Mb of the sequence. improved varieties of rice tolerant to drought, These have been functionally annotated and submergence and salinity, (ii) advance identification of new genes, analysis of breeding lines of rice with these traits, (iii) gene families and gene content has been trained human resource for MABB; and (iv) done. The analysis of abundance of information generation on markers for the chickpea transcripts within a tissue sample QTLs and their validation in the recipient led to the identification of differential and rice cultivars and genotyping. The project tissue-specific transcripts. Moreover, 4,111 envisages to improve at least 12 popular SSRs have been identified. The chickpea rice varieties grown in the rainfed agri-eco transcriptome has been published and systems within the country through marker- made publicly available through the assisted backcross breeding for flood, drought development of the Chickpea and salt tolerance. Transcriptome Database and transfer to the industry for the development of “Chickpea Challenge Programme on Chickpea Expression Microarray”. The whole Genomics Genome Browser for chickpea is under development, currently using one of the At NIPGR, New Delhi, nuclear genome of largest available contigs of the nuclear

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genome and contains the following tracks: Of these, 104 annotated proteins matched Gene (Overview), GC content (Region), and with Arabidopsis and 75 with rice, while CDS, Exon, Intron, 5’UTR, 3’UTR, Complex most other proteins were found in Repeats, tRNA, and Translation. different legumes [C. arietinum (91), Medicago (131), G. max (27), and P. sativum For manipulation of root architecture to (42)]. Further, 103 membrane associated improve abiotic stress tolerance, a putative proteins were identified from the CBL-interacting protein kinase (CIPK/sos2- membrane proteome. like protein kinase, PKS) was identified. The roots of the T1 seedlings were found longer Transcriptome sequencing of chickpea than the vector-control seeds. plants, inoculated with Ascochyta rabiei was done using the Roche 454 platform. The Functional analysis of inositol biosynthetic data was assembled to generate 68,942 genes is being done for which homozygous unigenes, with average contig length of 747 Arabidopsis transformed lines for each gene bp, N50 of 963 bp. (CaMIPS1 & 2) were generated and growth patterns under saline environment were To unravel the molecular events at various analyzed. stages of seed development and its nutritional status, transcriptome sequencing The water-deficit stress responsive of developing chickpea seeds at various proteome of chickpea was analysed which stages (10, 20, 30, and 40 DAA) was carried led to the identification of 773 proteins. out using the Roche/454 platform.

(A) (B)

Fig. 4.7: Differential and tissue specific expression analysis of chickpea transcriptome. (A) Transcripts preferentially expressed in each tissue sample as compared to others in tissue by tissue comparison For the transcripts in each cell, there is preferential expression in the column tissue than the row tissue sample. (B) Heatmap of the transcripts preferentially expressed in various tissue samples. The color scale (1100) represents RPM value. ML, mature leaf; FB, flower bud; YP, young pod.

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Functional annotation was done and contigs for developing various bio-fertilizers and were categorized as biological process, technology packages for their mass cellular component and molecular function. production and also focused on conversion Molecular analysis of important families is of industrial agricultural wastes into in progress. Currently, the development of biomanure and manage the organic waste comparative seed cytosolic proteome is in resources using low capital input protocols progress. without expensive laboratories and sophisticated industrial instruments. National Plant Gene Repository Microbial Consortia The Department has set up a National Plant Gene Repository (NAPGER) at Jaypee Institute of Information Technology, National Institute of Plant Genome Noida project studied plant growth Research, New Delhi. It is a National promoting microbes with Biofertilizer and facility for (i) storage and distribution of bio control properties to build a consortium plant genes, promoters and ESTs in form comprising both bacterial and fungi spp. of DNA clone, library, etc. and (ii) to Sampling of microbes was done from the develop a database for all stocks and other rhizosphere of different plant sp. such as information. The institute has procured banana, sorghum, millets, pumpkin, potato the necessary equipments, created and grasses. Isolates collected from the infrastructure for setting up the facility rhizosphere of sorghum and grasses were and also recruited the sanctioned particularly interesting as they were not manpower. The research protocols to be only withstanding high pH, but also followed in NAPGER have been showing tolerance to temperatures in upper developed. A web page has been mesophilic range of 35-400C. The developed and shortly an advertisement antagonistic effects were confirmed to would be issued to publicize the NAPGER develop a consortium. activities so that large section of scientific community is aware of it and gets Manipur University also developed benefitted. microbial consortia for the effective formulation of optimal strains of plant Biofertiliser Biotechnology growth promotion in rice and bio control against rice fungal and bacterial The Department has supported programmes pathogens. Actinomycete, Bacillus and

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Pseudomonas sp were the focus of the Vermicomposting study. After screening of the best strains in lab/greenhouse test, individual or Timber lignocellulosic wastes were mixtures of strains were subjected to inoculated with different combinations of the single or multi-site pot/field studies to fungi Phanerochete chrysosporium, Trichoderma learn feasibility for deployment of reesi, Aspergillus niger and the bacteria consortia of beneficial microorganism for Azotobacter chrococcum. Out of 10 microbial rice. Four isolates were identified. The combinations tested for pre-decomposition, culture filtrates did not show any the combination of P.chrysosporium + T.reesei inhibition against the fungal pathogens. was found best in terms of lingo-cellulosic In in vitro seed germination (vigor index) degradation prior to vermicomposting. The test was performed for three of the selected feasibility of bioreactive timber solid waste strains. vermicompost (TSWV) had also been validated for the first time.

Fig 4.8: View of vermi- entrepreneur using wood wastes as substrates

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Formulation of Mycorrhiza and alate traps, in situ termireactors, and termite Agriculturally Important Micro- harvesters. Pondicherry University had set organisms (AIMs) up an interactive web-based repository of all the information and the resources of The Energy Resources Institute (TERI), New information on termites-systematic, Delhi revalidated the PGP/BCA strains such distributions, niche, habitat, biology, as actinomycete isolates LSCh-10C, NRPI-18 substrate preference, role in natural and NRPI-18 and NRPI-26 and putative environments, control methods etc. Bacillus isolate CHDR. They established the co-habitation of AIMs with Arbuscular Biopesticides and Crop Mycorrhizal Fungi (AMF) to synergies their Management beneficial effects by developing a single bio- inoculants product that can improve plant A number of research projects have been growth by supplementing with nutrients. supported in the highly specific area for Six new unculturable endobacterial the control of pests and diseases of sequences were detected by the DGGE economically important crops, thereby analysis and 5 more after cloning of 16S enhancing the agricultural productivity for product directly. Endobacterial diversity sustainable development. Highlights of comprised both Bacillus related species as some of the project achievements are as well as bacterium-like organisms (BLOs). follows:

In case of termicomposting, Pondicherry Microbial Pesticides and Natural University, Pondicherry has completed the Enemies systematic survey of termite species with the species available and there relative At NCL, Pune Enzymes from a killed abundance has been established. Two types fungus (Myrothecium verrucaria) and conidial of multi-compartment termireactors preparation of entomopathogenic fungi designed. The multiple compartments (Metarhizium anisopliae, Beauveria bassiana and would enable to use different substances Verticillium lecanii) were produced in the simultaneously at each location and see the laboratory to control mealy bug for 2 relative preference of termites at that consecutive years (2009-2010 and 2010-2011). location for different feeds. Study has been In addition to the control of mealybug (50- undertaken towards captive colony 75%), M. verrucaria formulated enzyme development and preliminary designs of preparation reduced the infection level of

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downy mildew (Plasmopara viticola) and (Glomus bagyaraje) was developed. Data on powdery mildew (Uncinula necator) by 71% compatibility of nematophagous fungi and 76%, respectively in grapes. At Pochonia chlamydosporia and antagonistic Kuvempu University, Karnataka Survey of bacterium Pseudomonas fluorescens with AM Pest incidence as well as egg parasitoid on fungus (Glomus bagyaraje) was developed in Cylopelta siccifolia was completed. Laboratory vitro and in vivo. Again at IIHR, Bangalore experiment were carried out to know about a strategy was developed for the the hatchability and surveillances of C. management of disease complex in siccifolia. Aggregation and separation capsicum, okra, carrot, papaya, banana, behavioral study of C. cissifolia will be done gladioli and gerbera. Protocol of mass in the field. production of combination formulations of Pseudomonas fluorescens with Paecilomyces Data on compatibility of nematophagous lilacinus and Pseudomonas fluorescens with fungi Paecilomyces lilacinus and antagonistic Pochonia chlamydosporia was standardized. bacterium Pseudomonas fluorescens with AM Strategy of enrichment of vermicompost or fungus (Glomus bagyaraje) was developed in neem cake for the application in the main vitro and in vivo at IIHR, Bangalore. A field was also developed. Toxicological strategy of management of wilt disease data, shelf life data and bio-efficacy data of complex in tomato and capsicum using P. bio-pesticide formulations was also fluorescens and P. lilacinus with AM fungus generated.

A

B

C Fig. 4.9: A. Evaluation of bio-efficacy in gerbera under farmers field conditions being verified by member DBT task force along with the beneficiary farmer, B. Distribution of bio-pesticides to the farmers for field evaluation of bio-efficacy and C. Evaluation of bio-efficacy on Papaya under farmers field conditions

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Under tulticentre project implemented at confirmed the cultures belong to IARI, Pasighat and Mysore soil, plant and Pseudomonas and Bacillus group. seed samples were collected from different locations of Pasighat (Arunachal Pradesh) Botanical Pesticides and North India after recurrent field surveys. A total of 97 isolates of PGPR Study at Manonmanium Sundaranar were taken up for further characterization. University, Tamil Nadu studies were A set of isolates were screened against seed carried out for understanding the within- borne pathogens of cabbage, cauliflower plant preference in the rice leaffolder (RLF), and chilli from North east (Pasighat). Based Cnaphalocrocis medinalis (Guenée) on multiple screening, four isolates for ((Lepidoptera: Pyralidae) and its tomato and six isolates for cabbage were consequences for offspring performance on observed to be beneficial in better the host-plant Oryza sativa L. (TN, Ambai16, germination and seedling vigor. After a and IR20 varieties) concerning the role of sequence of screening in laboratory and induced resistance of rice plants to RLF pot culture, four best strains were feeding. The present study examined the identified and are being tested for seedling effects of induced resistance on the feeding priming under field conditions. Best strains (food assimilation and digestion) in green were given to Pasighat for further house and also the field cages. This study evaluation and Mysore centre for molecular also observed C. medinalis food utilization, characterization. In Pasighat centre, the best in order to estimate the possible influence strains received from IARI are being of induced resistance on C. medinalis feeding evaluated under pot culture and field. behavior. These results indicate that JA Citrus seedlings were also raised to test application induces systemic defenses in PGPR. The collaborating centre at Mysore rice that have a direct negative impact on has completed the biochemical tests and C. medinalis survival.

ABC Fig. 4.10: A. Field Cages, B. Rice leaffolder culture C. Effect of JA on rice leaffolder larvae (3 Mm)

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Entomopathogenic Nematodes (EPN) At TNAU, Coimbatore the survey was conducted under different agroclimatic At TFRI, Jabalpur seven native isolates zones comprising major Mango and Banana (TFRIEPN-08, TFRIEPN-15, TFRIEPN-23, growing areas and markets of Tamil Nadu. TFRIEPN-49, TFRIEPN-50, TFRIEPN-56 and Polyclonal antibody produced against 40 TFRIEPN-57) from banana, mango and two and 65 kDa mycelial protein exhibited the known isolates (Heterorhabditis indica and specific reaction with C. gloeosporioides and Steinernema carpocapsae) were maintained C. musae isolates respectively. By utilizing round the year. Laboratory culture of these PCA, presence of latent infection was fictitious host waxmoth, Galleria mellonella detected both in vitro and in vivo. RAPD- was maintained round the year, so as to PCR technique was utilized to determine obtain 300 mature larvae per day. The white the per cent similarity between the isolates grubs and their adults of three species of the pathogen. The SCAR primers were (Holotrichia rustica, H. mucida and H. able to detect the pathogen in fruit peel consanguinea) were collected from the forest tissue at 30 ng of infected DNA tissues. nurseries from central India. Field evaluation of the native EPN isolates was The crude extracts prepared from three initiated in the institute campus and in the common cultivars, three wild relatives (ICP selected termite mounds in the teak 15774, ICP 15815 & ICP 15868) and thirteen plantation areas. Experiments for bioefficacy wild accessions (ICPW 60 to ICPW 72) of of native species/ strains TFRIEPN-23, pigeonpea were tested for their proteinase TFRIEPN-49 and TFRIEPN-50 were carried inhibitory (PI) activity against bovine out against white grub species, Holotrichia trypsin, chymotrypsin and midgut trypsin- rustica, H. mucida and H. consanguinea in like proteinases of the following laboratory. lepidopteran insects: Helicoverpa armigera, Achaea janata, Spodoptera litura, Papilio Molecular Studies on Biocontrol Agents demoleus, Amasacta albistriga and Daphnis nerii. All the varieties of pigeon pea chosen in At S V University, Tirupati, the JHEH gene the present study possessed both trypsin was amplified, cloned and sequenced. A inhibitory (TI) and chymotrypsin inhibitory ~800 bp sequence of Bihar hairy caterpillar (CI) activity. The trypsin-like proteinase JHEH was obtained and analysed. This inhibitory activity of two wild relatives ICP partial JHEH sequence was found to have 15815 and ICP 15868 were found to be homology with other lepidopteron JHEH’s. highest in the following order: A. janata (>

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800 AJTI units), H. armigera (> 500 HATI Ltd., (PLSL) as an Industry Partner in a units), A. albistriga (> 35 AATI units) and P. unique public-private partnership model. demoleus (< 10 PDTI units). This program has contributed to the collection of microbes from different Development of comprehensive website biodiversity from all over India (the on bio-pesticide Western Ghats, North East, mangrove, marine environment, polluted sites etc.). The A comprehensive website on “Bio- largest collections of microbial cultures pesticides” has been developed. Salient (nearly 2,50,000) were screened for four achievements compiled from more than 250 different therapeutic targets. A total of 16123 completed projects have been included three stars hits were obtained of which 518 which will benefit scientists, entrepreneurs anti cancer, 3643 anti inflammation, 6676 and farmers. The website is under security anti diabetic and 5286 were anti infective check in NIC. activities. These potent cultures selected in the above exercise are being used to generate Bioresource Development and the list of 1000 cultures to be taken in the Utilization next phase of the program for identification of novel drug scaffolds. The National Bioresource Development Board (NBDB) accelerated R&D using In Phase II activity i. e. chemical modern tools of biosciences for characterization of selected hits of bioactives, development of new products and processes randomly selected 150 extracts were utilizing the rich biodiversity of our country. prepared and analyzed for chemical characterization. Additional 150 extracts Bioprospecting and product development have been prepared; analysis is in process and taxonomically diverse bacteria based Mission programme on microbial on ~4000, 16S rDNA sequences have been prospecting: drugs from microbes – a public generated. UPLC analysis and the private partnership dendrogram were obtained by identifying similar clusters of the chemical A Mission programme was launched in the fingerprinting analysis. year September, 2007 which involved partnership of 9 National Institutes & Action was initiated to explore the microbes Universities alongwith Piramal Life Sciences for many other biotechnologically useful

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products of industrial importance such as Repository would be set up as an production of industrially important independent Autonomous Institute for enzymes (i.e. Adenosine deaminases, nitrile Microbial Culture Sciences and Research hydratases, hydantionase, nitralases), and provide highest-standard services with screening for extracellular protease activity focused research on microbial ecology and for commercial purpose and identification systematics. of PKS genes from mangrove microbes etc. Prospecting of genes and molecules for Microbial Culture Collection Centre product development

The Microbial Culture Collection center Projects have been supported for prospecting (MCC) established at the National Centre of novel genes, molecules, enzymes etc. from for Cell Science (NCCS), Pune by the plants, microbes, fungi, lichens for Department of Biotechnology as the largest production of potential products of industrial culture collection is now an affiliate member importance. Novel genes/promoters, of the WFCC and is registered with the transcription factors were identified to WDCM. The MCC was recognized by the develop transgenics for biotic/abiotic stress WIPO Geneva as an IDA in April 2011. and for understanding different metabolic Currently, it holds greater than 2 lakh engineering pathway(s) operative in a cultures under various categories, such as system. Some of the technologies and normal, three-star, re-fermented, scale-up products developed from projects and and have been categorized based on the important leads are mentioned below:- degree of bioactive properties shown by them against cancer, diabetes, inflammation • In a programme aimed to prospect plant and infection. Majority have been tentatively and insect resources of the Western identified based on partial rRNA gene Ghats for important metabolites, sequencing. MCC has launched its own promising species from Icacinaceae website housed on the NCCS webpage. shown to produce high camptothecin MCC has begun to provide services to have been undertaken for domestication. academic and industrial establishments for Alternate sources of shikimic acid from microbial identification. The information of plants of the Western Ghats have been the molecular finger printing of the cultures identified and spatially mapped. Among has been added to the database. In the 12th the angiosperms, only two or three plan it is proposed that the Microbial plants Calophyllum apetalum had the

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highest level of shikimic acid. corosolic acid has been established in Gymnosperms species evaluated had Lagerstroemia speciosa and studies are detectable levels of shikimic acid. One underway to evaluate the plant extracts of the species belonging to the for anti-diabetic activity. Plant extracts araucariaceae family yielded the highest of Saraca asoca are being evaluated for levels of shikimic acid (5.02%). Isolation their anti-inflammatory activity. of anti-microbials from crude extracts of Microsatellite markers have been insect systems from the Western Ghats successfully developed and primers are has been carried out (Fig. 4.11). being designed to undertake population genetic study.

• In a programme aimed at Bioprospecting of selected lichen and plant species for product development against cancer and tuberculosis, MSSRF has isolated four novel compounds from lichen species (Fig. 4.12).

Fig. 4.11: Anti-microbial peptides from wasp venom

• A network project with eight institutions was initiated to bio-prospect for novel bioactive molecules from forest resources of the country. Populations of Dysoxylum binectariferum have been identified in Western Ghats and their distribution mapped. Significant variation in rohitukine have been Fig. 4.12: Ultra - structure of Lichen thallus- Secondary obtained (0.15% to 7.62%) and compounds – deposited on the hyphal wall derivitization of rohitukine and bioactivity against anti-malarial CDK’s • A biopesticide formulation (Bollcure) in progress. Similarly, variation in developed under DBT support from

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Eucalyptus has been transferred to two mycofumigation potential and industries. Central Insecticide Board has collaboration for product development approved the registration of “TERI-DBT is being finalized with Pest Control India Bollcure” for commercialization across Ltd. using the indigenous Muscodor spp. the India. Bollcure is environment friendly, suitable for both organic and • Under the project on mapping of marine IPM crop practices, suitable for green sulfur bacteria of India, eighty one conventional as well as Bt cotton, cost samples from marine habitats of Goa benefit ratio for cotton in 1:4.15 , cost and Gujarat were analyzed for genetic benefit ratio for chickpea in 1:17.1. culture and diversity of green sulfur bacteria. • Under studies on cold tolerant strains profile of the tolerance of altogether Characterization and Digitized 10 cold-tolerant strains and 4 Inventorization mesophilic strains to various environmental stress factors (viz, high Indian Bioresource Information Network temperature, freezing, high salt, high (IBIN) portal and low pH, oxidative stress, UV- radiation) were obtained. Remarkable The IBIN was approved for Spatial Node, variation was observed in the stress- Jeeva Manchitra at NRSC, Hyderabad and tolerance of cold-tolerant strains, Species node, Jeeva sampada at UAS, Banglore. obtained from the same environmental A set of six laboratories which linked their niche of Antarctica and also between databases with the IBIN have been identified the stress-tolerance of the mesophilic as BRICs of IBIN. The entire spatial and and Antarctic strains non-spatial data and also other related primary and secondary data is being hosted • Five Muscodor species have been on a special portal Indian Bioresource isolated from stem internal tissue of the Information Network. At IIRS Dehradun/ plant Cinnamomum malabaricum, NRSC, Hyderabad, national seamless C.camphora and from leaf of Aegle database of vetetarian type map, marmelos collected from Western Ghats biodiversity modeled outputs of and North Eastern Himalayas. Patent fragmentation, disturbance index and Application has been submitted on the biological richness at national level have new species of Muscodor with been prepared.

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Spatial Characterization different teams. This assessment has been done in a grid based manner and the Biodiversity characterization studies data has been compiled in the form of through satellite remote sensing and database. geographic information system was completed under the DBT-DoS project in DNA Barcoding 3 phases covering nearly 84 % of forest area. In Deccan Peninsula, 589 plant DNA Barcoding programmes were species recorded by information collected supported for generating barcodes for from spatially explicit, GPS tagged 1725 species of plants, insects and animals. In field plant inventory plots and DNA Barcoding of the birds, distribution and abundance information of approximately 1200 samples of birds have 881 species in Rajasthan, 313 species in been collected from various parts of India. Gujarat and 103 species in Lakshadweep DNA barcoding of 17 Phyllanthus species have been done. using the psbA-trnH region, 53 rattan species were successfully completed. A Quantitative assessment of plant resources digital database of Phyllanthus and Rattans in hot-spots of the country species was developed which includes a diagnostic key to the different Phyllanthus The programmes on mapping and species alongside their respective bar quantitative assessments of geographic codes. distribution and the population status of plant resources were completed for the Resource Based Network Programmes hot spots- Western Ghats, Eastern Ghats and North Eastern and Eastern Himalayan Several programmes have been launched to Regions with significant achievements. A screen, characterize and improve important first ever systematic attempt has been resources. Some important resources and made for quantitative assessment of plant interventions made are as follows: resources of Andaman and Nicobar islands. Several layers of Andaman and Honey Bee Nicobar Islands such as boundary, roads, rivers, places, water bodies etc were Under the ongoing network programme in digitized. Data inputting system was the Apiculture sector with focus on quality developed to load the data sheets from improvement, study of genetic diversity and

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development of molecular markers in Indian trait specific molecular markers, disease bee species, multiplexing of shortlisted resistance, low caffeine varieties. A network microsatellite markers has been project involving CCRI (Coffee Board), standardized. Two new lures have been CCMB (Hyderabad), UAS (Bangalore), MKU developed and effectiveness of these novel (Madurai) and CFTRI (Mysore) was plants based as well as the pheromone supported. A few stress responsive genes based honeybee attractant formulations is were cloned and validated for stress being evaluated. response.

Seabuckthorn Tea

Under the coordinated network project on Tea network was started with eight germplasm characterisation of institutes for improvement of tea, taking Seabuckthorn from different regions of the Tea Board along in all the programmes country, collection of accession continues with the institutes include, IHBT from across the country. Overall 488 Palampur, TRA Jorhat, UPASI, accessions of three Hippophae species Coimbatore, RRL Jorhat, NEHU Shillong, spread across Himalayas, namely, IIT Delhi, Delhi University and TERI, Hippophae rhamnoides, H. salicifolia and H. New Delhi. 1286 microsatellite primers tibetiana have been characterized were designed by sequencing of the morphologically for various descriptors positive clones derived from enriched and are being compiled for development genomic libraries and publicly available of a descriptor database. Chemical expressed sequence data in tea (Fig. 4.13). characterization of Hippophae leaf and fruit 622 of the identified microsatellite samples is being undertaken. markers were successfully validated in selected tea accessions and related Hippophae Germplasm Resource Centre has Camellia sps for their wider applicability. been established at Lahaul (HP) by IHBT, More than 3000 crosses were made for Palampur in collaboration with the Forest blister blight and drought resistance. 1058 Department of HP. mature seeds were germinated and these populations established at the nursery Coffee conditions. 644 F1 progenies derived from 32 different crosses were established in The thrust of the study was on developing the field condition.

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Fig. 4.13: Characteristics of microsatellite markers identified in tea

Zingiber variety have been micro propagated. Micro rhizome induction has been observed in 266 Multilocation trials for turmeric were plantlets and 150 are under primary completed in Sikkim, Assam, Meghalaya hardening stage. and Manipur. Technology for micro and mini rhizome production from ginger, Sugarcane turmeric and Kaempheria sp. has been optimized and transferred to AVS, Kottakkal The genomes of potyvirus isolates (SCMV for mass production for medicine & SStMV) infecting sugarcane and sorghum manufacture. All the collected samples have were partially sequenced. The full length been analyzed for their chemical genome of SStMV is determined and its compositions. The curcumin content of the genome organization and phylogenetic collected turmeric varieties ranged from 1 relationships were elucidated. Tissue culture to 11% and trans-geraniol content for protocols for development of somatic collected varieties of ginger ranged from 23 embryogenesis by different media to 36%. 1252 plantlets of ginger for Nadia combinations have been optimized.

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Antibiotic sensitivity test was conducted to regions (three different states viz. Haryana, determine optimum concentration for Rajasthan and Gujarat) of the country. selection of putative transplastomics using different antibiotics. 30 novel functional Bamboo markers based on conserved intron scanning primers were developed for the first time, Under the network program, 9 major states through the comparative analysis of publicly (Andhra Pradesh, Karnataka, Tamil Nadu, available expressed-sequence data of Gujarat, Himachal Pradesh, Uttaranchal, sugarcane, sorghum and barley and, the Kerala, Rajasthan and Haryana) and all the whole rice genome-sequence survey. 80 7 states of North East were covered. EST- SSR primers were synthesized based Demonstration programme completed its on the sequences available in public domain tenure in 18 states covering 978 ha and 103 genomic SSR (gSSR) primers were efforts are being made to consolidate the synthesized based on the sequences. performance data from all demonstration projects in the form of a booklet detailing a Gums and resins package of practices for Bamboo cultivation. Tissue culture/micro propagation The protocols were standardized for technologies have also been developed at metabolite profiling of C. wightii. A range various R&D institutes for different species. of chemically diverse metabolites including organic acids, fatty acids, amino acids, Capacity Building sugars and carbohydrates, sterols, cyclitols and terpenes were characterized using GC- DBT’s Natural Resource Awareness Club MS. Most of the metabolites identified in this study are not reported earlier in C. DBT Natural Resource Awareness Clubs wightii. Using high-field NMR spectroscopy (DNA Clubs) Program is aimed giving 43 metabolites were identified from different young school students (Class 6-12) a well plant parts of C. wightii which includes rounded exposure to the fascinating world primary, secondary and intermediates of of bio-resources by implanting a suite of pathways. Some of the identified mutually complimenting set of activities that metabolites (other than guggulsterones) may focus on various dimensions of bio- have high commercial value. Germplasm of resources and seamlessly blend with formal 78 accessions has been collected from school curriculums. DNA Clubs program is different locations from Commiphora growing being implemented in 190 schools spread

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across 20 States/UTs involving more than VI-X from 8 northeastern states are directly 11,400 student members each year. DNA involved through 249 lectures, 830 Program has designated coordinator(s) experiments and hands on activities, 121 nominated by the school management for Audio Video shows, 160 field visits to each partner school. The RRAs are different biodiversity rich areas and supported by a dedicated Program institutes of higher learning. Management Unit set up by DBT for management of the programme. Rural Bioresource Complexes

DNA Clubs Program activities across 190 The Department has established Rural Bio- schools resource Complexes to demonstrate viable and ecologically compatible technologies to S. Activity (2010-11) Number the rural people for adoption in a holistic No. and sustainable manner. In the first phase, projects have been funded at five State 1 Guest Lectures 745 Agricultural Universities (SAU). An 2 Institutional Visits/ 952 independent study on the Impact Field Trips assessment of Rural Bioresource Complexes in terms of its socio-economic benefits that 3 Audio Visual Shows 966 have been transferred to the community was commissioned by DBT to Mott MacDonald 4 Laboratory Experiments 1828 Pvt. Ltd., Noida. The planned interventions 5 Vacation Training 18 of respective SAUs and the implemented Programs interventions, as observed in field have been compared, which revealed that the number DBT-TERI Mentoring Schools for North- of activities have increased in almost all the East Region of India institutes. Most of the institutes have conducted baseline study at the initial phase The DNA clubs: DBT-TERI mentoring of the project. From this evaluation study schools of northeast is being implemented it was found that the Bio-resource through partner institutes in 361 high complexes have made major impact in schools. Two days orientation for extending certain recent interventions to the coordinating teacher has been completed for community and all the research institutes 7 northeastern states. 22650 students of Class have done their work precisely. The Rural

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Bio-resource complexes have initiated and Village, West Garo Hills District and so popularized a progressive approach in far thirty two varieties were planted in this integrated farming based livelihood germplasm bank. generation. Plant Biotechnology Rural Bioresource Complex in North- East India at North-Eastern Hill The department supported programmes in University, Shillong the area of Plant Biotechnology on basic research, forestry, horticultural and The Rural Bioresource Complex in North- plantation crops, metabolomics etc. East India at North-Eastern Hill University, Shillong has been established. Two Basic Research institutions viz., North Eastern Hill University (NEHU) and ICAR Complex for Studies continued on signal transduction N.E Hill Region are involved in pathways in plants to understand the implementing the project; ICAR is mechanism involved in response to responsible for demonstration farming of external stimuli and the process of Megha 1 turmeric and Khasi Mandarin, adaptation to these changed environmental while the remaining activities of the project conditions. are the responsibility of NEHU. Collection and ex-situ vivo conservation of 32 Citrus At University of Hyderabad, role of different varieties have been collected from signaling molecules was studied on stomatal Meghalaya. For extraction of turmeric and closure in pea. It was observed that levels ginger oleoresin and oil, an extraction plant of reactive oxygen species (ROS), Nitric has been established at Laskein Village, Oxide (NO) were found to increase on Jaintia Hills District, and is ready for exposure to abscisic acid (ABA) or Methyl production. The mechanical drying and Jasmonate (MJ). The relative kinetics of powdering units have also been installed increase in ROS, NO and cytosolic pH was at Laskein village. Mechanical de- also observed. There was a strong evidence starching, drying and powdering of to indicate that cytosolic pH, ROS and NO turmeric have successfully been tried. Trial interacted with each other. production of oleoresin is being undertaken. A Citrus field germplasm bank Molecular basis of potassium nutrition/ (10 ha) has been established at Bibragre signaling and functional analysis of calcium

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mediated CBL-CIPK (calcineurin B-like and Plant growth and development is the CLB interacting protein kinase) network result of controlled cell proliferation under potassium deficient conditions was where MCM (mini-chromosome main- studied in Arabidopsis, at UDSC, New Delhi tenance) proteins (DNA replicative and six interactors of C1PK9 were identified. components) play essential role in DNA Further, in order to carry out functional replication. The MCM2-7 or MCM4/6/7 analysis of selected candidate target, complex has been reported to function homozygous knock out mutants of VDAC3 as DNA helicase in animal and yeast (voltage dependent anion channel) and systems. Genes encoding all the six AP2C alleles have been developed and MCMs subunits (MCM2-7) from pea have over-expression transgenic lines of VDAC3 been cloned and the encoded proteins and AP2C generated. have been purified. Transcript of MCM6 was up-regulated in salinity and cold In order to understand interaction between stress in pea plant. MCM6 protein was auxin and sugar signaling pathway, a study shown to be localized in the nucleus and was supported at NIPGR, New Delhi. It cytosol. MCM6 single subunit self- was observed that glucose not only affects interacts and forms a homohexamer which auxin signaling genes but also affects auxin is active for DNA helicase and ATPase biosynthesis and perception. Besides, activities. MCM6 over expression driven glucose signaling affects auxin transporter by a constitutive CaMV-35S promoter in P1N2 levels, partioning and auxin polar tobacco plants confers salinity tolerance. transport assay. Microarray analysis further revealed that glucose and auxin control a Solanaceae Genome Initiative large number of genes both agonistically and antagonistically. India was a part of International Solanaceae Genome programme and was assigned the Study was supported to understand responsibility of sequencing 12 Mb membrane biogenesis at IIT, Madras. enchromatic region of chromosome 5. This Subcellular membrane of chloroplast from task was given to UDSC, New Delhi ( 5Mb spinach leaves and vacuoles from beetroot region), IARI, New Delhi (5Mb) and NIPGR have been isolated and first evidence for (2Mb). The sequencing has been completed presence of biogenic membrane flippase and the physical map of the entire genome (ATP Independent) and ATP dependent of tomato is now available. This would flippase activity have been reported. help in identification of agronomically

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important genes/allele markers linked to Disease Resistance important traits under Target Induced Local Lesion in Genomes (TILLING) During Phase-I two transgenic lines resistant programme at University of Hyderabad. to Tomato Leaf Curl Virus (ToLCV) using For TILLING, facility has been established antisense replicase gene have been developed at Hyderabad. with dual resistance against virus and insect infestation. Five mapping populations have Functional Genomics been generated to identify the source of ToLCV resistance and variety LA1777 has been Nutritional and shelf life improvement found to show resistance across India. Besides, SSR, ISSR and SCAR markers have been Metabolic profiling of tomato fruit at various identified and validated for linkage to ToLCV. stages of development has helped in Basic information generated during Phase-I is identifying genetic loci controlling the being taken further during Phase-II to develop characteristics that are related to nutrients tomato verities with broad spectrum resistance and shelf life of fruits. The leads obtained to ToLCV and Tospo virus by appropriate are being taken up further and phase II gene deployment strategy through marker programme is being initiated to enhance aided selection. nutrient levels such as flavonoids, carotenoids and folate, using induced Network Programme on Metabolomics mutations/ transgenic manipulations and enrichment of Total Soluble Solids (TSS) in A network has been initiated on fruits for making tomato suitable for Metabolomics focusing on crops like tomato, processing. Study is also being initiated on rice, potato, maize, Arnebia, Curcuma etc. genome analysis of SNP’s/mutations/ Its major focus has been to develop transcript/proteome in cultivars and the complete metabolomics profile of potato, wild accessions of tomato using whole understand metabolomics of tomato with genome sequencing and reverse genetic reference to fruit quality, aroma, nutritional tools for improving desired traits. quality, study changes in transcriptiome, Transgenic tomato lines expressing proteome and metabolite profile in maize polyamine genes under fruit specific (as induced by Nitrogen and Phosphorus promoter for post harvest quality have been stress), secondary metabolite pathway developed and are being tested for post related to shikonin synthesis (Arnebia), harvest quality traits. metabolomics related to stress and disease

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resistance (rice) and assessment of rhizoctonia system. On the basis of therapeutic properties in curcuma. virulence, isolates identified have been grouped into five clusters. Three isolates At IIHR, Bangalore two lines of tomato 249- have been confirmed as Rhizoctonia oryzae 15-4 and IIHR-2101 have been found to have both by morphological studies as well as higher values for fruit quality parameters. by ITS (Internal Transcribed Spacer) Metabolite profiling of the selected lines sequencing. Further studies on biochemical has been done for volatile flavour, and molecular events during the host carotenoids and Vitamin- C parameters pathogen interactions and also biotic and while profiling for organic acids, phenolic abiotic elicitor based induction resistance acids and flavonoids is in progress. in rice Rhizoctonia system are going on.

Host Pathogen Interaction At UDSC, New Delhi and TNAU, Coimbatore studies are underway to Studies were supported to isolate and understand the interaction between cassava characterize secreted salivary gland proteins mosaic virus and carrier (whitefly). Protocol (SSGPs) from rice gall midge (Orsalia oryzae) has been standardized for inoculation of to understand their role in rice-insect pest cloned SLCMU (Sri Lankan Cassava Mosaic interactions at ICGEB, New Delhi. SSGPs Virus) DNA and its whitefly transmission have been cloned to generate recombinant in the laboratory host Nicotiana tabacum. SSAPs proteins. Antibodies have been raised Plants have been generated using wild-type against a select sub-set of recombinant viral DNA and the transmission through SSAPs. Rice hosts when injected with whiteflies has been achieved. Besides, in - recombinant insect SSAPs showed reactions vitro interaction studies on viral CP and such as tissue necrosis and typical GroEL proteins of whitefly endosymbionts hypersensitive reaction was observed in is in progress. resistant hosts. Currently these recombinants are being bulked up for use in plant Madurai Kamraj University has found C2 interaction studies. protein of Bhendi Yellow Vein Mosaic Virus interacting with karyopherin – as well as At Bidhan Chandra Krishi Vishwavidyalaya with itself, suggesting that it may be Kalayani, a study has been supported to functioning as a dimer. Further the C2 understand the role of biotic/abiotic elicitor protein has been shown to transactivate a induced systemic resistance in rice- host promoter. The micro RNA binding

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properties of these proteins are being dot blot hybridization which was further studied. confirmed by RT-PCR. Complete genome (7379bp) of 3 isolates of Cherry Virus A Viral movement protein encoded by AV2 (CVA) has been cloned and one of them ORF and the coat protein (CP) encoded by sequenced. It showed 81 and 84% similarly AV1 ORF of a monopartite begomovirus, to the type isolate at the nucleotide and cotton leaf and kokhran virus-dabawali amino acid level respectively. This study (CLCuKV- Dab) have been cloned and over- provides the first report and the complete expressed in E.coli at IISc, Bangalore. The nucleotide sequence of Cherry Virus A from purified E.coli expressed CP has been shown sweet cherry in India. to interact specifically with single stranded DNA via Zinc finger motif with H85 as most Colocasia (taro) and Amorphophallus (elephant crucial residue in the motif. CP was shown foot yam) tuber crops and aroid ornamental to interact with AV2 by ELISA and surface plants were surveyed in AP and screened Plasmon resonance. The insect and these for virus infection using DAC-ELISA using markers can be used in plant expressed CP heterologus potyvirus antisera. Varying localized in the cell periphery. percent infections with plant species and locations was observed. Further, electron At IIHR, Bangalore, four isolates of Cucumber microcopy of Colocasia dip preparation Mosaic Cucumovirus Virus (CMV) have been revealed the presence of flexous collected and characterized. Study on filamentions particle characteristics of mechanism of CMV resistance showed that polyvirusis. Besides, partial genome in VC246 variety no virus replication was sequence analysis of potyvirus isolates observed and cell-cell movement of the virus associated with infection on Colocasia, was also restricted. Inheritance studies using Caladium and Dieffenbachia species revealed six generation mean analysis of perennial that isolates are phylogenetically closely and Pusa Jwala showed single recessive gene related to Konjac Mosiac Virus ( Ko MV) – for CMV resistance. Further molecular Zan reported from Taiwan, and this is the marker linked to CMV resistance in Chilli first observation on natural infection of has been identified and could be used in aroids with KoMV in India. marker assisted breeding programme. Forestry, Horticulture and Plantation crops IHBT, Palampur has identified viruses infecting plum and cherry by ELISA and A network project on molecular marker

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based breeding in eucalypts was initiated free tissue culture raised citrus (Nagpur at the Institute of Forest Genetics and Tree Mandrain) planting material through shoot Breeding, Coimbatore to develop genetic tip micro grafting has been undertaken. linkage map and Quantitative Trait Loci (QTLs) identification for two industrially In order to reduce the cold-induced important traits i.e adventitious rooting sweetening in potato, study was supported capacity and wood property traits. at CPRI, Shimla. Seven INV RNAi transgenic Mapping populations for the cross between lines were evaluated along with wild type E. camaldulensis X E. tereticornis, E. control Kufri-Chipsona-1 under confined camaldulensis X E. grandis and E. tereticornis field condition. Yield of two transgenic lines X E. grandis were generated through ( K.Chiplnv RNAi-2214 and 2123) have been controlled hybridization. Field planting of found comparable to non-transgenic wild F1 hybrids was completed to clonally type control Kufri-Chipsone-1. Transgenic propagate the hybrids for multi- tubers were cold stored at 20C and its environmental phenotyping. The hybridity chipping performance was evaluated. of the F1s are being confirmed using the Further development of marker-free potato simple sequence repeat (SSR) markers. transgenic with improved cold-chipping Seventy SSR loci were analyzed for the attributes is being evaluated under glass polymorphism between the parents to house conditions. generate species-specific linkage map using pseudo-testcross strategy. Studies have been supported on chemotyping and gene expression profiling An efficient protocol has been developed in black pepper at Kerala Agriculture for multiplication of carnation plants at IIHR, University, Trissur. Piperine content has Bangalore. A new variety IIHRP1 was been estimated in different stages (native developed and validated in farmers fields green, native red and dried) of berries in and it has been approved for release as seven black pepper genotypes using HPLC. ‘Arka Flame’ by Karnataka State varietal Dry samples showed more piperine content release committee. Another variety IIHRIS- than fresh samples. Further, during berry 1 has been named as ARKA Tejas and development, piperine synthesis was found identified for pot cultivation. It is valuable to begin in the berries 50 days after spike for academic interest and is registered with initiation. Cloning of candidate genes NBPGR as a valuable genetic stock. Large related to secondary metabolic pathway is scale production and demonstration of virus underway.

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A study was supported at IIHR, Bangalore Apple Network to identify markers linked to fruit quality in Guava. Two different mapping At NBPGR, New Delhi, study was supported populations have been raised and used to develop a protocol to cryopreserve apple for genotyping studies. Genotyping has dormant buds. Natural chilling of budwood been carried out for parental lines, to was found to be the pre-requisite for post- screen parental polymorphism by using a thaw recovery. Budwood when procured set of 237 microsatellite markers. The from high altitudes where temperature was identified polymorphic markers have been upto zero for weeks, responded after selected for high throughput genotyping cryopreservation. Besides, grafting and patch of the mapping population. budding was found to be season based.

Fig.4.14: Regeneration from leaf explants of apple rootstock, MM106: (A) leaves (B) callusing at excised leaf base (C-E) Indirect shoot regeneration (F) rooting of micro-shoots (G-H) GUS expression on putatively transformed leaf explants

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Plants Under Hi-Tech Polyhouse Hardening of Plants

Hardening of Plants

Rootstocks Planted under Field Fig. 4.15: Tissue culture raised apple plants being transferred to the field A network programme on Apple was IHBT, Palmpur efforts are being made to supported at IHBT Palmpur, TERI, New identify the viral pathogens infecting apple Delhi and CSKHPKV, Palampur under by devising a single assay to which a tissue culture based protocol for simultaneously detect several pathogens mass production of plants has been at a time. Besides, descriptors are also developed. The germplasm collected being developed. An Apple germplasm under the network is being screened for repository of elite germplasm collected virus infestation, nearly 240 samples from various regions of the country has collected have been screened and 105 been set up at Badarwah Campus, Jammu samples have been found positive. At University, Jammu.

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New initiatives of Information Technology, Hyderabad to develop a metabolomic relational database Saffron Network and develop models of metabolite pathway networking and software suitable for A Brain Storming Meeting was organized at predicting networks of metabolite University of Kashmir, Srinagar to evolve a formation, analysis/storage and retrieval of program on induction of variability for genetic metabolites. improvement of Saffron, transcriptome analysis to identify genes and regulatory National Certification System Tissue elements that determine floral development Culture Raised Plants and size of corm, development of tissue culture protocol for corm production of DBT is successfully implementing the desired size, development of agrotechnology National Certification System for Tissue for using cormlet of small size and Culture Raised Plants (NCS TCP) since last characterization of microflora of rhizosphere five years. The salient achievements of the associated with Saffron with a target to programme are as follows: develop consortia of beneficial microbes. Tissue culture production facilities have Metabolomics been recognized based on infrastructure, technical competency and package practice A network project on tomato metabolome of production of tissue culture plants. So has been supported at three institutes far 57 companies which have met the including Jammu University, UDSC, New necessary criteria have been recognized. Delhi and Hyderabad University. It will cover identification of metabolites from Nine Test Laboratories which are accredited natural accessions followed by mutants and by the NCS-TCP have started functioning transgenic lines, identify regulatory genes for extending services to the tissue culture and proteins regulating these metabolic industry. ATLs are now operational and pathways. Subsequently, it would undertake have tested approximately 7850 samples of pathway manipulations to increase/decrease various crops from different companies. the levels of desired metabolites in tomato. Awareness Programme on NCS-TCP Another network has been been supported at JNU, New Delhi and International Institite Fifteen programmes were organized

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successfully at Lucknow on March 25, 2011 of novel bioactive agents, development of with 136 participants from different herbal formulations, genomics and segments such as State Horticulture/ biosynthetic pathway studies. The salient Agriculture officials, tissue culture achievements of the programme during the production facilities, representatives of year are as follows: Accredited Test Laboratories, representatives of growers’ society, nurseries and Ex-situ conservation, reproductive progressive farmers. The participants were biology and agrotechnology trained for production of economical crops including banana, sugarcane, potato, vanilla. Important medicinal plants of Manipur Initiative has been taken to develop hills such as Paris polyphylla, Curcuma standards for new species potential for angustifolia and Zingiber zerumbet have been propagation through tissue culture. collected and maintained in the germplasm Guidelines for “Testing of mother plants/ bank at Krishi Vigyan Kendra – Sylvan, stock culture” and “Renewal of Recognition” Senapati District, Manipur. Work on have been developed and approved. reproductive mechanism of Picrorhiza Standard Operating Procedures (SOPs) for kurrooa, Valeriana wallichii and Ferula ATLs and TCPFs have been revised and jaeschkeana in natural habitats was relevant formats have been streamlined and completed at BGSB University, Rajauri, adopted. Certification label has been revised J&K. Seed germination studies on Dioscerea and approved for issuance by ATLs to tissue vilosa and Panax sp were carried out at culture production facilities towards Nagaland University, Mokochung. certification of tissue culture raised plants. Evaluation of the performance of tissue- Awareness has been created across the culture raised rose scented geranium country among all stakeholders through (Pelarganium graveoleus) in Maharashtra state organization of state level awareness continued jointly in collaboration with programmes. Kelkar’s Scientific Research Centre, Mumbai and Vidya Pratishthan’s School of Medicinal and Aromatic Plants Biotechnology, Baramati. About 10,000 rooted cuttings of geranium were raised A programme on biotechnological and distributed to the farmers of Baramati intervention on medicinal and aromatic district for field trials after a training plants (MAP) was continued for programme. Demonstration on cultivation conservation, isolation and characterization and processing of selected aromatic crops

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was also undertaken over an area of 50 zeylanicum and C. cassia significantly acres in Dhar block of Punjab state with decreased the NO level in murine joint collaboration of Kelkar Scientific macrophage cell lines – RAW 264.7 and Research Centre, Mumbai and Punjab State J774.1 at Interactive Research School for Council for Science & Technology, Health Affairs, Pune in collaboration with Chandigarh. an industrial partner – M/s Natural Remedies Pvt. Ltd., Bangalore. These A network project for identification of high extracts resulted into decrease in mRNA camptothecin yielding clones and expression of proinflamatory cytokines ILLb development of agrotechnology sustainable and TNFa in cell lines. Work on isolation harvesting methods in Nothapodytes and characterization of anti-cancer nimmoniana is continuing at UAS, Bangalore, compounds from edible mushrooms has UAS, Dharwad (College of Forestry, Sirsi) been initiated at Indian Institute of Chemical and Research and Action in Natural Wealth Biology, Kolkata. Administration, Pune. Protocol was standardized for extraction and estimation Administration of methanolic root extracts of camptothecin from leaf tissues of N. of Coix lachrymojobi at various doses nimmoniana. Over 5000 seedlings of N. effectively inhibited poisonous snakes (Naja nimmoniana were introduced into various naja and Daboia russelli) venom induced agro-forestry systems and coppicing lethality in mice at NMAM Institute of technology to maximize camptothcin yield Technology, Udupi. Myotoxicity induced by was developed. Efforts were initiated to both poisonous snakes venom in rats was develop diagnostics for better management significantly neutralized by the root extract of begamoviruses infecting Mentha spp at of C. lachromojobi. Ethanolic extract of CIMAP, Lucknow. Tinospora cordifolia was found highly active against human epithelial cancer stem cells Novel bioactive agents and herbal in a study jointly undertaken at Manipal formulation University, Manipal and Indian Institute of Science, Bangalore. Investigations on extracts Double-blind, randomized placebo of Withania somnifera and Withaferin A for controlled clinical trials continued on water their ability to inhibit the phenacetin O- extract of Terminalia arjuna in patients with deethylation activity of CYPIA2 using left ventricultuar dysfunction at AIIMS, New human and rat liver microsomes was Delhi. Methanolic extracts of Cinnamomum initiated at NMIMS, Mumbai.

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Studies were initiated on monoherbal Salient achievements in the R&D preparation and their phytochemical programmes were: constituents against Hepatitis-B virus jointly at Institute of Liver and Biliary Sciences, Transgenics New Delhi and CIMAP, Lucknow. Significant anti-Hepatitis-B activity was At CCMB, Hyderabad, a knockout mice recorded in the extracts of Phyllanthus amarus model was developed by deleting Wdr 13 and Silybum marianum in in vitro tests using gene in mouse embryonic stem cells Hep G 2.2.15 and Hep G2 cell lines. through homologous recombination to analyze its role in obesity and Genomics and biosynthetic pathways metabolism. The interacting portions of the Wdr 13 protein viz. PHIP, ERá, ERâ, Eleven genes involved in mucilage HDAC1, HADAC2 and HDAC7 which play biosynthetic pathway were identified in important role in the regulation of a wide Isabgol (Plantago ovata) at University of variety of cellular functions were identified. Jammu, Jammu. Efforts were made for These mutants were bred in the background isolating the key regulatory genes of db/db knockout animals which will help responsible for santalol production in in understanding the structure of Wdr13 and sandalwood (Santalum album) at Vittal Mallya db locus. Scientific Research Foundation, Bangalore. Studies on designing and preparation of Attempts are being made to express human microarray chip to analyze the terpene proteins of therapeutic value in the milk of pathway in aromatic plants is progressing buffalo at NII, New Delhi. A full length at CIMAP, Lucknow. promoter of buffalo beta casein gene was isolated, cloned, sequenced and Animal Biotechnology-Production characterized in terms of its activity. The green fluorescent protein (GFP) was cloned Efforts continued to enhance the under this promoter and MCF 7 cells productivity of livestock. During the (human breast cell line) were transfected in period, two brain storming workshops vitro. The construct was used to generate were organized in the areas of poultry transgenic mice for checking in vivo activity biotechnology and lignocelluloses of buffalo beta casein promoter. The breast degradation and priority areas were gland of lactating females of F1 progeny of identified for generating new programme. mice confirmed its activity.

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Animal Reproduction and Related Areas of ovulation of Mithun cows with spontaneous and superovulatory estrus The role of imprinting cluster on rat respectively. chromosome during embryogenesis was studied at NIRRH, Mumbai. The study Efforts are also on to conserve quality Yak confirmed that the imprinted genes regulate germplasm and its multiplication at NRC embryo growth whereas aberrant expression on Yak at Dirang, Arunchal Pradesh. Yak of imprinted genes was associated with embryos were developed in vitro up to embryo growth disorders. The study blastocyst stage where as Yak hybrid confirmed that paternal administration of embryos could be developed upto morula tamoxifen led to aberrant expression of stage. A few of the embryos developed imprinted genes in the F1 embryos which were transferred to the recipients and presumably abrogate Notch and Wnt pregnancies were confirmed. Some of the signaling leading to cell cycle arrest, embryos were cryopreserved using affecting embryo-placental growth and vitrification method. The ovum pick up development and ultimately causing (OPU) technique for harvesting embryos embryo loss. from live Yaks was also standardized in collaboration with NDRI, Karnal. Efforts were taken to enhance the productivity of Mithun at NRC on Mithun, Sperm specific antigens with immuno- Medziphema, Nagaland. The artificial contraceptive potential were identified, insemination technique and preservation isolated and characterized in dogs at of Mithun semen were successfully GADVASU, Ludhiana. Dogs and bitches standardized and calves were produced were immunized against purified PH-20 using cryopreserved semen both at farm and LDHC sub units of antigen to observe and field levels. The protocols for their effect on sperm parameters and superovulation and ETT were also fertility. Immunofluoresence of anti-PH and standardized. Mithun cows were LDHC sub units with dog spermatozoa superovulated using FSH and recovered indicated scattered localization of PH-20 sub embryos were transferred in to the recipient units on the entire head surface and that of animals. Out of six embryos transferred to LDHC sub units mainly on the acrosome. the recipient, two animals maintained The study confirms that LDHC and PH-20 pregnancy. It was found that hCG @ 1500 antigens have immunocontraceptive IU and 3000 IU was optimum for induction potential.

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The effect of zinc (Zn) supplementation on cycle followed by a significant decrease of growth, immune response and reproduction expression during the mid and late luteal of female rats were conducted at SVVU, phase and a further decrease of VEGF Hyderabad. The study indicated that 12 mRNA after regression. These results ppm Zn supplementation in feed was suggest an important role of VEGF in optimum for growth, while 36 ppm angiogenesis of the newly formed CL in was required for obtaining higher buffalo. immunocompetence in rat model. The serum progesterone concentration was found to be Estrus-specific pheromones were assessed higher in rats with Zn supplemented feed for their possible role in early pregnancy compared to standard feed and the ovarian detection in buffalo at Bharathidasan histology indicated lower percentage of University, Truchirappalli. Various estrus atretic follicles along with higher antral specific compounds were evaluated and 4- follicles and well developed corpus lutea methyl phenol was found promising for with 24 and 36ppm of Zn supplementation estrus detection. The estrus stage urine respectively. The Zn deficiency was found sample gave considerable elevated colour to depress body weight gain, feed intake, change with 4- methyl phenol compared to immune response and reproductive other stage of urine samples. The estrus efficiency. specific urine also showed significant result in the absorption spectra at 558 nm. Efforts Expression and localization of autocrine and are on to develop an estrus detection kit paracrine factors and their receptors using urine samples. regulating corpus luteum (CL) function during the estrous cycle of buffaloes was Genetic Characterization and Genome studied at IVRI, Izatnagar. All the vascular endothelial growth factor (VEGF) isoforms The satellite tagged genes of water buffalo, were found in the buffalo CL during the Bubalus bubalis were characterized at NII, estrous cycle. Analysis of the VEGF New Delhi. Four RsaI repeat fragments transcripts showed that CL predominantly viz. pDp1, pDp2, pDp3 and pDp4 of 1331, expressed the two smallest VEGF isoforms 65, 603 and 339 base pairs, respectively of i.e. VEGF120 & VEGF164 and weakly buffalo were cloned and sequenced. These expressed the VEGF 188 isoform. The highest fragments were found to represent retro- VEGF mRNA expression was detected transposons and part of some functional during the early luteal phase of the estrous genes. RsaI repeats were found to be

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transcriptionally active in somatic tissues allele), the frequency of functionally and spermatozoa. The pDp1 showed important alleles is low at other analyzed maximum activity in lung; pDp2 and pDp3 loci, suggesting the need for screening of in kidney and pDp4 in ovary. The study the breeding bulls before selection. suggests that RsaI repeats have been incorporated into the exonic regions of The fecundity of local sheep breed of various transcribing genes, possibly Kashmir is being enhanced by introgressing contributing towards the architecture and fecundity B (FecB) gene at SKUAST, Srinagar. evolution of the buffalo and related During the course of the study, the genomes. reproductive performance of the animals with introgressed Fec B gene was reported The genetic diversity and population to be a litter size of 146% against 86-92% in structure of different Indian zebu cattle the sheep without Fec B gene. The study breeds were studied at NBAGR, Karnal. All also confirmed that the Fec X mutation the breeds analyzed other than Nagori and conferring high litter size in the Kashmir Kangayam had substantial within breed sheep was not segregating and the existence genetic diversity with moderate levels of of Fec B gene in such animals ruled out. A breed differentiation. The genetic distances new mutation in exon 2 of Fec X gene showed close grouping of Mewati and between 1022-1243 bp area was also Kankrej cattle whereas Kangayam and observed. The study helped in enhancing Nimari cattle exhibited highest genetic the productivity of local sheep breed. In difference. Majority of the breeds from North another study, the productivity and and North-Western region grouped reproductive efficiency of Lonand strain of separately from that of breeds from Southern Deccani sheep was also enhanced at farmer’s region. The mitochondrial D-loop based level by introgressing the mutation of Fec B analysis on 20 cattle breeds revealed that by crossbreeding at NARI, Phaltan. The litter Southern, draft purpose and grey coat color size of Fec B carrier sheep was increased breeds are more diverse. The and to enhance the chances of their survival, phylogeopraphy and network analysis a small quantity (~200 gm per day) of revealed Southern breeds to be primitive in supplementary feed to the ewes just before comparison to Northern cattle breeds. The lambing to about two months after lambing candidate gene analysis across the breeding was found to be cost effective and could bulls utilized in artificial insemination yield double the profit per ewe as compared revealed that except at Beta-casein locus (A2 to non-carrier ewes.

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Animal Nutrition control diet. The dressing percentage and edible organs percent was also increased as Tannin degrading bacterial isolates were the Sheanut cake percent increased in the isolated and evaluated as a probiotic to ration along with inclusion of probiotics. improve utilization of tree leaves containing The study revealed that the Sheanut cake high tannin at IVRI, Izatnagar. A total of 69 can be safely utilised as a feed ingredient tannin degrading bacterial species were up to 40% level with or without probiotics isolated from the rumen of goats fed on oak in sheep and buffalo calves to reduce the leaves / pakar leaves as major roughage cost of production of meat and for effective source. Out of 69 tannin rumen bacteria utilisation of unconventional feed stuffs. isolated, 22 isolates showed improvement in IVTD of oak leaves. The isolates exhibited Utilization of agro-forest based non- good tannase activity and tannin degrading conventional oil cakes as an alternate to oil ability. On the basis of biochemical cakes as a protein source in feed was taken characterization, bacterial isolate TDGB 406 up. The feeding trials of detoxified was used as a probiotic for the feeding trials jatropha, karnaj and neem oil cakes were in goats and improved growth performance conducted in small ruminants to validate and FCR was found in goats fed on oak their potential use as protein supplements. leaves as one of the main roughage source. It was found that detoxifiied jatropha and neem cakes can be used as a replacement Efforts are underway to utilize Sheanut cake of soya bean meal to up to 75% level in the as an energy supplement in livestock diet of sheep and goats without any adverse feed to replace high cost low energy effects on nutrient utilization, nitrogen supplements like deoiled rice bran at metabolism, immune response and meat SVVU, Hyderabad. Chemical analysis of quality. Detoxified karanj, on the other hand, Sheanut cake confirmed high amount of can be used at a maximum of 50% level of crude protein, crude fibre, minerals and replacement of conventional protein meal. essential amino acids. The experiments in Encapsulation process for feed enzymes was sheep and buffalo calves were carried out developed at SVVU, Hyderabad to improve to study the growth, nutrient digestibility their heat tolerance and storage stability. and economics of meat production. The dry Studies on storage and thermal stability of matter intake and average daily weight gain commercial enzymes viz. amylase and was significantly higher in the animals fed xylanase indicated that the activity of these with Sheanut cake rations compared to enzymes declined slowly in the encapsulated

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form where as in the non-encapsulated forms micronutrients. Immunity of cattle was the activity declined rapidly even during found to be enhanced significantly with the storage at room temperatures. The sugar supplementation of micronutrients. The milk release activity in feed of amylase and yield was also enhanced with the group xylanase was not influenced by encapsulation of cattle with micronutrient feed. of enzyme at pelletization temperature of 700C for four minutes. However, there was a Poultry significant retention of amylase and xylanase activity in encapsulated enzyme at both 800C Molecular evaluation of forced moulting in and 900C of pelletization for four minutes. white leghorn hens and its possible effective The results indicate that the encapsulation alternatives were studied at CARI, Izatnagar. of amylase and xylanase enzymes with The differential expression patterns of sodium alginate offers protection against candidate genes (apoptotic and cytokine) thermal inactivation. responsible for regression/rejuvenation of reproductive tissues of white leghorn hens Studies on the effect of micronutrients during forced moulting were studied and supplementation on immunity and few critical genes (Caspase 1, Caspase 2, productivity of indigenous cattle were Caspase 6,BOK, Bcl 2, p53, IL1, IL6, IL10, conducted at NDRI, Karnal. The TRAIL, T and TG) responsible for regression/ micronutrients supplementation significantly rejuvenation were identified. A new method reduced oxidative and metabolic stress of forced moulting using Zinc and Chromium during calving period. Leptin levels were was developed which can be effectively used found to decrease before calving and at the commercial scale and also complies remained low after calving period. Insulin with the animal welfare norms. concentrations differed according to days postpartum: levels started to decrease before QTL markers for growth traits were identified parturition, minimum concentrations were in broiler chicken at PDP, Hyderabad. Three found around parturition but levels were strains of chicken viz. PB-1, CB and IWI were fully recovered after 30 days postpartum. generated to explore polymorphism of Plasma concentrations of GH increased at myostatin promoter. A total of 4 haplotypes parturition and remained elevated after were found across the populations. The calving. There was a significant increase in haplotype, h1 was the most predominant the levels of leptin, insulin and growth allele in all the populations, while the least hormone in cows supplemented with frequent haplotype varied from strain to

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strain. The haplotype combinations showed Animal Health significant effect on body weights at 6 weeks in PB-1 and IWI lines and 7 weeks at CB The department has been implementing line. In PB-1 line, h4 showed the highest programs in animal vaccines and diagnostics growth rate both between 4-6 and 6-7 weeks. and collaborative and coordinated research In CB line, h3 group had the highest growth for the translation of existing candidate rate between 6-7 weeks. The relative vaccine technologies and diagnostics for expression profile of myostatin gene in field use through product development to different haplogroups revealed that h1h2 commercialization. haplogroup had the highest expression as compared to other haplogroups suggesting A “Translational Research Platform for a significant role of the gene in regulating Veterinary Biologicals” (TRPVB) has been growth in chicken. established at Tamil Nadu Veterinary and Animal Sciences University (TANUVAS), Efforts were made to enhance the Chennai in September 2011 in partnership productivity of Emu at MVC, Chennai. Male with DBT. This platform would facilitate Emu birds were trained for semen the translation of technologies by performing product development, ejaculation using an artificial cloaca validation, obtaining regulatory approvals fabricated by the investigators. So far, three to facilitate product commercialization and male Emus were trained efficiently for also be a referral center to strengthen ejaculation procedures. The average daily linkages and collaboration in the area of output of semen from the trained emus was animal vaccine and diagnostics observed at the rate of 0.3 ml to 0.7 ml. The development, exchange of biological initial motility of the spermatozoa ranged materials, technology assessment, between zero to 40 per cent. Sex supporting training, consultation and determination technique for Emu is being intellectual property development. standardized.

Fig. 4.16 : Diagrammatic representation of services offered by TRPVB

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International experts were involved in and challenges for development of reviewing the progress of Network Project Brucellosis Network Project were discussed. on Classical Swine Fewer for smooth With the recommendation of international running of the program and to overcome and national experts a Network Project on the shortcomings of the results of swine Brucellosis was formulated and fever network project under CSF Network recommendations were made to set up six programme one National and five Regional Epidemiology units, two Repositories, two referral CSF laboratories have been projects for development of animal and established in different regions of the human vaccines respectively, three projects country. Rapid and precise diagnostic tools for development of diagnostic kit for animal for CSF: (TaqMan)-reverse transcriptase (RT) and one project on bioinformatics related PCR assay was developed for detection of work. Five papers have been published in CSFV in tissue samples originating from national and international journals through pigs suspected for CSF. Isolation and the projects funded. adaptation of CSFV in PK-15 cells along with production and characterization of Vaccines and Diagnostics projects monoclonal antibodies against CSFV was implemented are summarized as under: carried out. Seroprevalance and molecular biological A mini workshop on “Health Monitoring of approach for diagnostics of canine Laboratory Animals” involving potential monocytic ehrilichiosis in various regions users and selected stakeholders was of India organized at IISc, Bangalore was organised for discussion on important diseases of A total of 350 canine samples were small laboratory animals relevant to Indian processed using nested PCR targeting 16s subcontinent that need to be screened rRNA gene for detection of E. canis, of which periodically, various parameters which a total of 19 samples have been detected needs to be considered while monitoring positive for E. canis and one sample for the health of experimental animals like Anaplasma platys as also confirmed by number of animals screened, collection of sequencing their PCR amplified products. right specimen, usage of appropriate PCR for detection of Babesia which is also method, etc. The workshop of DBT Network a tick borne disease has been standardized Project on Brucellosis was held in August, and out of a total of 409 samples screened 2011 at NII, New Delhi in which the issues by this PCR , 76 have been found positive,

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as also confirmed by sequencing their PCR Development of recombinant fusion protein amplified products. Indirect Fluorescent vaccine for Mycobacterium avium sub Antibody Test for estimation of antibodies sp. Paratuberculosis against E. canis from canine serum samples has also been standardized and data on The fusion clones of 85A and 85B gene of clinico-pathological changes in E. canis bacteria were generated and expression was infection is being recorded. confirmed. Chitosan nano particles were produced and assessed for their characters. Development of vaccine for control of Preliminary studies with heat killed chitosan bovine tuberculosis coupled MAP vaccine and 85A+85B fusion antigen were found to be safe and resulted The animals were clinically examined; in Th1 and Th2 response. blood samples were collected for routine haematological assessment, baseline Identification of target molecule on B cells detection of intracellular cytokines in T cell which binds Infectious Bursal Disease subsets (CD4 & CD8) and screening for (IBD) virus and its regulation for mycobacterial pathogens by molecular immunoprophylaxis of IBD in chicken beacons and culture was done. The animals were immunized with live BCG and heat The investigation could lead to valuable killed Mycobacterium W, recombinant BCG new insights into the identification of the over expressing SOD and 85C antigens. For target which can be an effective therapeutic DNA vaccines the intra-muscular (rump) and be used for prophylactic measures for and rBCG vaccines the intra-dermal (neck the control of this important infectious left and right) route of immunization were disease which causes huge economic losses used. After immunization blood samples to the poultry industry worldwide. were collected at various time intervals. Experimental studies carried out have The PBMC have been isolated from the yielded new results which indicate that animals at each time point and cryo- MHC class II molecule present in large preserved. These samples were revived for quantities on immature B cells in the bursa in vitro assessment of immune response to of young chicks is the putative target for mycobacterial antigens during the extension the IBD virus. The binding of IBD virus to period by real time PCR for cytokines chicken MHC II molecules on developing B and other related immunological para- cells in the bursa prevents their interactions meters. with the non-lymphoid bursal cells which

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is essential for their survival and cellulolytic and amylolytic microbes was maturation. Thus, blocking of MHC II on carried out at Kakdwip Research Centre of immature B cells by IBD virus in chicken CIBA. This study was undertaken to identify Bursa may lead to apoptosis in B the potential of isolated cellulolytic and cells causing large scale destruction of B amylolytic microbes from the gut of cells and hence immunodeficiency in young brackishwater fishes by supplementing them chicks. in the diet of Seabass (Lates calcarifer) and Mugil cephalus (Grey mullet) in feed Aquaculture and Marine utilization efficiency and digestibility. The Biotechnology in vivo trial on M. cephalus juveniles revealed that fermented ingredients could replace In Aquaculture & Marine Biotechnology 75% of fish meal in diet of Mugil cephalus programme, projects were supported on juveniles without affecting growth rate, FCR, aquaculture feed, development of PER and survival. Supplementation of live therapeutic feed, identification of novel bacterial mixture (Bacillus subtilis DDKRC5 bioactive molecules, marine extremophiles, and Bacillus sp. DDKRC1) or feeding of molecular characterization, induced microbial fermented ingredients could maturation in shrimp, production of male reduce Vibrio load in water though total ornamental fish, and development of microbial load in water did not differ molecular markers for disease resistance, significantly when compared with tank diagnostics and vaccines, in vitro model for water of control. Feed supplemented with a viral replication, development of cell lines mixture of Bacillus subtilis DDKRC5(CCx) & etc. An Indo-Norway joint collaborative Bacillus sp. DDKRC1 (LC8) showed higher programme on fish vaccine development weight gain (141.42±2.76%), lower was implemented. Technologies were FCR(2.15±0.03), higher nutrient digestibility, developed and patented with the leads better gut microbial and digestive enzyme obtained, along with a good number of status in Asian seabass juveniles. publications in this programme. Some of the important achievements of the The studies on immunostimulatory property programme are as follows: of seeds of Achyranthes aspera (Ameranthaceae) in Indian major carp Catla Aquaculture Feed catla was carried out at Delhi University. The larvae of C. catla were fed with diets Development of enriched aqua-feed with containing raw seeds and crude extract of

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seeds with control diet. Fish were challenged shrimp aquaculture can fully be prevented, with Aeromonas hydrophila after one month as the newly developed product, of feeding. Group of fish exposed to UV-B Asparagopsis diet is a natural algal-based radiation (80 μW/ cm2) for 10 min for 40 product, which will not have environmental days were fed with seeds of Achyranthes consequences as recorded in the use of aspera. Incorporation of seeds of Achyranthes antibiotics. It was found that haemogram aspera in diet of fish showed promising profile of the medicated shrimp enhanced results to overcome the problem of UV-B considerably when compared to the control radiation in aquatic system. Feeding of carp groups. Similarly, the agglutination titer, larvae with seed at 0.5% level improved serum bactericidal activity and phagocytic the non-specific immunity at early rates of the medicated shrimps were higher. developmental stage and it enhanced the The PO activity of the 1.2 g/kg treated resistance of fish against the pathogen. shrimp group (10.7 ± 2.8) was higher than Dietary supplementation of seeds resulted that of control (4.8± 3.2). Based on the results in enhanced growth rate of fish. Best it can be concluded that Asparagopsis performance was found in raw seeds incorporated feed at a dose level of 1.2 g/kg incorporated diet fed carp, but the diet significantly improves survival, growth and containing either extract of the seeds showed yield under real farm conditions. promising results. Induced maturation in shrimp Shrimp Therapeutic Feed Molecular signalling for induced ovarian An Integrated Disease Management (IDM) maturation of P. monodon was studied at System for Sustainable Shrimp Farming was University of Madras, to overcome the developed at Bharathidasan University, problems of excessive loss of hemolymph Tiruchy. A therapeutic feed was formulated and susceptibility to infections faced in from marine red alga, Asparagopsis taxiformis traditional eyestalk ablation process. for the management of Vibriosis in Penaeus Molecular signal interventional approach monodon. The product developed is suitable using MEK inhibitor has been used as an to be used as an alternative to antibiotics. alternative technique. The expression of The efficacy was proved in statistically phospho ERK was predominantly detected designed experimental trials conducted in the eyestalk XO-SG complex of control through in vitro, in vivo, in captivity and field animal. Gonadosomatic index (GSI) was trials. The consequence of the antibiotics in assessed for the ovarian maturation. The

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shrimp treated with inhibitor attained fully related to metabolic pathway of various mature stage and spawned at ~96 hrs, organisms. This strategy would be useful where as unilateral eyestalk ablated shrimp to identify the disease resistance gene and spawned at ~144 hrs. Statistical analysis also to understand molecular mechanism of showed a highly significant increase (P<0.05) white spot disease in P. monodon. in the mean of GSI of shrimp treated with inhibitor over ablated and control shrimp. In another project, improvement of disease The shrimp showed excellent response to resistance in rohu carp and tiger shrimp this inhibitor treatment than eyestalk was undertaken by developing marker ablation. The study could lead to alternative resource, real time expression analysis, method to induce maturation in shrimp. survival data analysis and immune parameter studies including screening of Disease Resistance Molecular Markers microsatellite markers. The results suggest that innate immunity is enhanced in native A project on identification of disease resistant line fish because higher quantities resistant giant Black Tiger Shrimp, Penaeus of particular compounds are expressed, and monodon using molecular markers was because of the presence of particular implemented by Bose Institute, Kolkata. polymorphisms, or linked genes. This has With this aim, highly statistically significant demonstrated the utility of identifying genes DNA marker of 455 bp by RAPD method associated with disease resistance. A number was identified to screen the disease-resistant of the putative rohu SNPs were tested and shrimp populations and disease susceptible these are ready for use to perform a populations. An attempt was made to thorough scan for genes associated with screen disease resistant P. monodon among disease resistance. wild populations at four different geographic locations in the East cost of India In vitro model for WSSV replication as well as 35 different cultured ponds using DNA marker. Challenge experiment was A project was undertaken to develop an in also carried out in screened shrimp with vitro system from Penaeus indicus and WSSV. The sequences were subjected to freshwater crab Paratelphusa hydrodomous for NCBI mega blast to find homology with WSSV replication, pathogenesis and other sequences and showed similarity with quantification at C. Abdul Hakeem College, mainly two types of proteins such as TN. An attempt was made to develop an membrane bound protein and proteins in vitro system from marine shrimp (Penaeus

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indicus) and freshwater crab (Paratelphusa Abdul Hakeem College, TN. A RT-PCR hydrodomous). The results of PCR and based assay and a prototype kit for the Western blot revealed the presence of WSSV detection of betanodavirus causing Viral in hemolymph, eye muscle, gill and heart Nervous Necrosis (VNN) in fish was tissue of freshwater crab and these organs developed and standardized. The assay and were found to be highly susceptible to WSSV kit have been validated extensively using and more suitable for WSSV propagation. field samples of clinically and sub-clinically The transcriptional and translational infected fish (freshwater, brackishwater and analyses of VP28 gene of WSSV in different marine) from different parts of the country. organs of WSSV-infected crab revealed the The kit can be used for the routine diagnosis multiplication of WSSV in heart tissue, gill of disease, besides as a management tool to tissue, hemolymph and muscle. In vitro screen broodstock, larvae and even trash system was successfully developed using fish used as feed in fish hatcheries and also heart explants of freshwater crab. The heart in developing specific pathogen-free stock explants were maintained in viable condition development. using modified EX-CELL 405 cell culture medium without serum for more than 50 days. The results of PCR, RT-PCR, Western blot, histology, and immunohistochemistry revealed the replication of WSSV in heart explants of crab. The overall results revealed that the heart explants of freshwater crab was found to be a promising in vitro system for WSSV replication and also for screening antiviral substances against WSSV.

Development of RT-PCR kit for the detection of fish nodavirus

Fig.4.17: Betanodavirus assay prototype kit A collaborative project on characterization and development of diagnostics for viral Marine Carotenoids nervous necrosis in sea bass (Lates calarifer) and mullet (Mugil cephalus) was Isolation of carotene-protein from shrimp waste implemented by CIBA, Chennai and C. by autolysis technique was carried out by

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CFTRI, Mysore. Autolysis conditions were transcript analysis of novel gene Serine standardized to prepare carotene-protein isolate Proteinase and alpha-2- macroglobulin from rich in antioxidant activity. Antioxidant activity shrimp Fenneropenaeus indicus was carried of crude carotenoid extract from shrimp waste out by Alagappa University. Alpha-2 and its fractions was evaluated by in-vitro and macroglobulin (A2M), a non-specific in-vivo techniques. Different in-vitro antioxidant protease inhibitor involved in host defense, assays indicated the strong scavenging activity is a glycoprotein found in almost all of shrimp waste extract and the astaxanthin taxonomic categories of animals. As fraction separated from crude carotenoid extract. proteinase inhibitor, it regulates protein The extracts were also able to inhibit the degradation activity in tissues. The oxidation of lipids in liposome membrane expression of serine proteinase were model system. The antioxidant activity of the analysed in different tissue of F. indicus and extracts was demonstrated through in-vivo the mRNA transcripts were analysed after studies using rat feeding experiments. the injection of bacterial challenge with Carotenogenic bacteria were isolated from Vibrio (V. harveyi & V. parahaemolyticus). The marine environment and their ability to tissue expression profiles and challenge- produce carotenoids was evaluated. The induced expression of these genes were conditions for extraction of carotenoids from assayed. Three A2Ms isoforms were Flavobacterium sp. were also standardized. The identified in F. chinensis and it has been hydrolyzed protein isolate showed higher found that the sequence of F. indicus A2M antioxidant activity compared to that obtained have high similarities (82%) with FcA2M-1. by the pH shift method. The proteins are This suggests that the different types of A2M broken down to smaller units and the carry out different functions and are not low molecular peptides result in higher simply functionally redundant. Functional antioxidant activity of the hydrolyzed proteins. studies on shrimp A2Ms in F. indicus would The protein isolates also contain a considerable help to elucidate A2M defence mechanisms amount of carotenoids. Thus the protein and and also clarify the evolutionary relationship carotenoid rich protein isolate obtained from between A2M-FI and its molecules. shrimp waste would find use in aquaculture nutrition. Bio-active Compounds

Genomic Characterization A collaborative project on characterisation of bioactive compounds from marine Genome characterization and mRNA Mollusc and Porifera that regulate

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osteoclastogenesis was implemented by Kochi. Eighteen cell lines have been ACTREC, Navi Mumbai and the D. G. developed from 4 species of commercially Ruparel College of Arts, Science and important marine fishes i.e. Cobia Commerce, (DGRC), Mumbai for exploiting (Rachycentron canadum), honeycomb grouper the source of potent bioactive compounds (Epinephelus merra), rabbit fish (Siganus as marine natural products. Incremental canaliculatus), and the marine ornamental fish changes in the rate of bone resorption can Dascyllus trimaculatus. Three cell lines were lead to bone disruption and cause major developed from the fin and caudal peduncle bone diseases, including osteoporosis, bone of the three spot damsel, Dascyllus metastasis, and rheumatoid arthritis. The trimaculatus. Six successful cell lines have marine extracts of mollusc Turbo brunneus been developed from various tissues of the and porifera Tethya spp. showed a good cobia, Rachycentron canadum. Cell culture antiosteoporotic activity in ovariectomised systems have been developed from the mice model. Inhibition of osteoclastogenesis honeycomb grouper, Epinephelus merra. These was shown by TME and its fractions. Raman cell lines were cryopreserved in liquid spectroscopy studies showed increased nitrogen and their subsequent revival mineralisation in the bones of mice treated showed >80% survival rate. The cell lines with TME and SPPE. Ovariectomised mice are being characterised by chromosome were used as estrogen deficient model for analysis, immunophenotyping, transmission studying antiosteoporotic effect of marine electron microscopy and molecular extracts Turbo Methanol Extract (TME) and techniques. Petroleum Ether soluble portion of methanol extract (SPPE). Oral administration of TME Development and characterization of cell and SPPE to ovariectomised mice could lines from Etroplus for virological and reduce the increased bone resorption and toxicological applications was implemented trabecular thinning and leading to bio- at C. Abdul Hakeem College, TN. Cell lines prospecting of novel bio-active compounds from tissues of eye, gill, kidney and brain from marine species. of Etroplus suratensis were developed and characterized. These cell lines showed Cell line development predominantly epithelial-like cells. Effects of temperature and foetal bovine serum Establishment and characterisation of cell concentration on the growth of these cell lines from selected marine food fish and lines were examined and optimum growth ornamental fish was continued at CMFRI, was found at the temperature of 28oC with

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20% foetal bovine serum. All the four cell Andhra Pradesh. The isolated â-galactosidase lines were successfully cryopreserved and producing deep marine bacterium from Bay- revived at different passage levels. The cells of-Bengal was investigated by 16S rRNA, of these cell lines were successfully FAME, biochemical and TEM analysis and transfected with pEGFP vector DNA. The was identified as gram negative, spiral eye (IEE), gill (IEG) and kidney (IEK) cell shaped, motile belonging to the class lines were found to be susceptible to Alphaproteobacteria and the genus Thalassospira. nodavirus but resistant to infectious The optimum growth temperature and pancreatic necrosis virus (IPNV). tolerance against the salt concentration suggested that the isolated bacterium was At CUSAT, Kochi a growth medium categorized as haloplanktic psychrophile. exclusively for shrimp lymphoid cell culture Moreover it has shown 10% to 30% of β– was developed as a major block in the galactosidase activity at 5oC to 15ºC, whereas establishment of cell lines from shrimp due the thermal stability of the enzyme was to lack of a specific cell culture medium for 0oC to 30oC at pH 6.5. A comparative docking the cultivation of shrimp cells in vitro. A study of psychrophilic β-galactosidase novel cell culture medium named SCCM with lactose, ONPG, and PNPG against (Shrimp Cell Culture Medium) has been the β-galactosidase from mesophilic and developed and validated exclusively for thermophilic sources revealed that shrimp cell culture in-vitro and monolayer psychrophilic β-galactosidase showed more of lymphyed cells developed in SCCM binding affinity towards the three substrates medium. This has helped in identification when compared with other two sources. The and removal of blocks on in-vitro enzyme has shown high specific activity at transformation and establishment of low temperatures when compared with permanent cell lines from Penaeus monodon. mesophilic and thermophilic enzymes. A patent application has been filed through DBT. Indo-Norway Collaboration on Fish Vaccine Marine Extremophiles A multicentric Indo-Norwegian programme Studies on isolation, cloning and production on vaccine platform was continued. Work of industrially important cold adaptive on development and evaluation of bacterial enzymes from marine extremophiles were (Aeromonas hydrophila and Edwardsiella tarda) carried out at Acharya Nagarjuna University, vaccines for finfish based on outer

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membrane proteins (OMP) was initiated at rosenbergii nodavirus was carried out with College of Fisheries Mangalore. Aeromonas the collaborative efforts of CIFA and CIBA. hydrophila is responsible for serious Based on the sequence analysis of three economic losses for fish-farming industry MrNV genes (Capsid, RdRp, B2), the due to serious disease manifestation in a tertiary structure was predicted using I- number of ways such as fin rot, tail rot, TASSER software. In the absence of any hemorrhagic septicemia, dropsy, ulceration, therapeutics to control white tail disease asymptomatic septicemia, exophthalmos etc. (WTD) in Macrobrachium rosenbergii, A recombinant vaccine was developed recombinant proteins of M. rosenbergii against this pathogen. Fish immunized with nodavirus (MrNV) may also act as this recombinant protein was found to be immunomodulators against the disease by highly protected (RPS ~ 65%) when targeting the viral genes. The MrNV RdRp challenged with A. hydrophila. The vaccine and capsid protein were able to reduce was highly immunogenic as seen from the the viral load after a 14 day post challenge. high antibody titre recorded in immunized Sequence similarity in different viral fish, level of which was maintained for over isolates, the nucleotide and amino acid two months. Edwardsiella tarda is also a major sequence of MrNV capsid gene was concern to the aquaculture industry. A studied and compared to Thai, Taiwanese, recombinant vaccine was also developed Chinese and Belize MrNV isolates. The against this pathogen. Fish immunized with phylogenetic analysis based on the this recombinant protein were seen to be sequence comparison of MrNV capsid highly protected (RPS ~70%) when gene, revealed that the Indian isolate was challenged with E. tarda. The vaccine was close to the Thai isolate when compared highly immunogenic as seen from the high to other geographical isolates. antibody titre recorded in immunized fish, the level of which was maintained for over Seribiotechnology two months. The study indicates the potential of the OMPs for protecting carp Programme was continued on improvement and rohu through vaccination. of productivity, enhancement of silk quality, host-plants interaction and post-harvest In another programme, work on processing of silk along with utilization of Immunomodulation studies in freshwater by-products in sericulture. A new initiative prawn Macrobrachium rosenbergii using on application of silk protein was recombinant proteins of Macrobrachium undertaken as potential biomaterial.

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Significant achievements made are silkworm (Antheraea mylitta) have been summarized. initiated at Kakatiya University, Warangal. Ethological and morphological Development of improved races of characteristics of four ecoraces of tasar silkworm for enhanced productivity silkworm – Andhra local, Daba TU, Daba BV and Bhandara at different stages of life BmNPV resistant strains of silkworm cycle have been recorded. (Bombyx mori) have been developed using marker-assisted breeding jointly at Efforts were made to develop protocols for Seribiotech Research Laboratory (SBRL), cryopreservation of eggs and embryos of Bangalore and Andhra Pradesh State silkworm (B. mori) at Central Sericultural Sericulture Research and Development Germplam Resource Centre, Hosur. A Institute (APSSR&DI), Hindupur. These method for dechorination of silkworm eggs strains have shown about 40 to 50% survival of 10 accessions of multivoltine and when challenged with BmNPV as compared bivoltine races has been successfully to 10% survival in CSR-2 lines of silkworm developed. used as control. Efforts were continued on identification of DNA markers linked to Development of Diseases Control cocoon traits at CSR&TI, Mysore. EST-SNP Measures primers have been identified to be closely linked to the quantitative trait loci (QTL) Efforts were continued on biochemical and controlling the filament length and denier molecular characterization of events traits. Diapause specific genes have been following uzifly infestation of silkworm at identified in the eggs of multivolatile SBRL, Bangalore. Immune response proteins silkworm (B. mori) through suppressive such as chaperones, cytokines, signal subtractive hybridization at SBRL, proteins and proteolytic enzymes in Bangalore. Work has been initiated on silkworm were identified. Life cycle features cloning, expression and characterization of of microsporidians infecting tasar silkworm yolk protein receptors from mulberry (A. mylitta) and muga silkworm (A. assama) silkworms (B. mori) and eri silkworm (Samia have been studied. synthia ricini). Improvement of Host Plants Studies on ethology and hybrid compatibility of various ecoraces of tasar Multiple test mapping populations have

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been raised by crossing two powdery mulberry at UAS, Bangalore. Mapping mildew resistant and three susceptible populations segregating for root traits and parents towards validation and utilization WUE have been established for construction of SCAR marker for powdery mildew of linkage map in mulberry using the co- resistance in mulberry jointly at CSR&TI, dominant SSR markers. Berhampore and CCMB, Hyderabad. A novel AP2/EREBP family surface wax- Post-harvest processing of silk related gene called MiSHN has been cloned and characterized from mulberry jointly at Studies have been continued on two University of Agricultural Sciences, microbial dyes – Bluish Violet and Scarlett Bangalore and CSR&TI, Mysore. Over- Red for their dying characteristics and dying expression of MiSHN cDNA in tobacco process optimization jointly at IICT, (Nicotiana tabacum) resulted in an increase Mumbai and Bhavan’s College, Mumbai. in leaf surface wax leading to delayed post- Optimization of dying process parameters, harvest water loss. dying kinetics and improvement of fastness properties through application of mordents A consortium project on Mulberry of these dyes has been successfully Genomics (CPMG) involving four accomplished. Significant improvement in institutions – CSR&TI, Mysore, CSGRC, fastness properties have been achieved with Hosur, UAS, Bangalore and UDSC, New mordenting of silk fabrics. Delhi has been continued. Genotyping of 72 exotic mulberry germplasm using SSR Utilization of by-products markers has been completed jointly at CSR&TI, Mysore and CSGRC, Hosur. Four Process for recovery of sericin from the soap mulberry genotypes having high water use alkali as well as from industrial silk efficiency (WUE) and high root growth – degumming liquor has been standardized UP, MS-3, Himachal local and Dudia white at pilot plant set up by IIT, New Delhi have been selected for transcriptome-based jointly with an industrial partner. SNP discovery, identification and Application of sericin on polyester fabric characterization of novel stress specific has been found to impart value-added genes jointly at UAS, Bangalore and UDSC, properties to the finished product such as New Delhi. Genomic SSR markers have improved moisture regain, antistatic been identified by adopting the behaviour, antibacterial and ultra-violet microsatellite enrichment strategy in protection.

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Silk Proteins as Potential Biomaterials Bacterial/Microbial Functional Genomics

Silk based supermacroporous cryogel Studies conducted by researchers in BHU matrices have been synthesized by showed the role of anti-ant sigma factor in cryogelatin technology for exploring their conferring resistance to several cell wall potential in cell-material interactions at IIT, active antibiotics including first, second and Kanpur. Silk fibroin-agarose cyrogel third generation cephalosporins indicating composites showed fast swelling kinetics, novel mechanisms of antibiotic resistance high-water uptake and good flow rates. in bacteria. These have shown good cell attachment and proliferation properties during At DU South Campus functional expression interaction with fibroblasts. Efforts have of full length channel rhodopsin in yeast been initiated on utilization of commercial expression system was reported. Further silk waste as potential nano-biomaterial at work is being carried out to elucidate the RV College of Engineering, Bangalore. spectral and structural characteristics of the Process for extraction and preparation of light-gated ion channel protein. nano sericin material has been standardized. Work conducted by scientists at IISc has shown a single mammalian mitochondrial Basic Research in Modern translation initiation factor to functionally Biology replace two bacterial factors (IF1 and IF2). Leads showed that the ribosome recycling The department through basic research factor (RRF) known to disassemble post- programme in Modern Biology has been termination complexes contributes to supporting a number of research projects to recycling of ribosomal complexes stalled at increase the basic competency of basic the step of elongation in E.coli. research. Important leads obtained in many of the basic research studies led to Cellular and Molecular Immunology strengthening of applied research and better understanding of the basic principles. A Studies were conducted on the expression number of research programs were and function of nucleotide binding supported during the period. Noteworthy oligiomerization domain proteins in achievements of some of the projects are macrophages on treatment with presented below: peptidoglycan at BHU. The findings

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revealed that PGN induced iNOS expression EhCaBP3 using solution NMR. The in mouse peritoneal macrophages is a structural analysis showed that this protein secondary effect in which PGE2 plays an is partially folded with a well folded N- important role along with other autocrine/ terminal domain and an unstructured C- paracrine signaling molecules such as IFNα, terminal counterpart. Structural studies TNFα, INFα. carried out at IISc Bangalore on acetate kinase (AcKA) which shares homology with In a study carried out to investigate chronic PduW and TdcD have led to the inflammatory disease like arthritis at Vittal identification of a novel ligand pockets Mallya Scientific Research Foundation has which could be important for enzymatic led to the first time report to relate and regulation. establish involvement of NFkB induction to other cytokines in IL-1 signaling in human synovial sarcoma cell lines

Fig.4.18: RT-PCR analysis raise in different cytokines (Cox- 2, ICAM, VEGF, MMP-1 and MMP-2 after NFkB activation indicating inflammatory from synovial sarcoma cells Fig. 4.19 : Tertiary structure of S. typhimurium AckA treated with IL-1 for 1,3,6,12 and 24 hours (GAPDH-internal illustrating the small (domain-I) and large (domain-II) Control) domains of StAckA. The core secondary structural elements (âââáâáâá) are shown in green (strands) and cyan (helices), while insertions of subdomains between secondary structural elements are highlighted in magenta (strands) Structural Biology and yellow (helices)

Scientists working on structural and Scientists working at ACTREC, Mumbai on functional aspect of calcium sensor proteins structural and functional characterization of from E.histolytica at JNU have shown the RAP80: a novel h-BRCA1 interacting protein three dimensional solution structure of involved in the mediation of DNA damage

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repair have reported change in the protein in DNA repair. Studies on molecular folding of RAP80 wt, BRCA1 wt and mechanism of pathogenesis of glaucoma at pathogenic mutants. The information is CCMB have shown that glaucoma associated being generated for further determining the mutations causes alteration in interaction of residues important for genomic integrity and optineurin with cellular proteins and this for drug discovery. leads to defect in function. Optineurin regulates signaling through transcription Cell and Molecular Biology factor NF-kα, by mediating interaction of an enzyme CYLD (deubiquitinases) with its Work undertaken to functionally characterize substrate RIP; a glaucoma causing mutant HAMP domain in osmosensing at IMTech, (H486R). Chandigarh have shown that HAMP domain is crucial for osmosensing by DhNiklp Biochemistry & Biophysics (group III hybrid histidine kinase) and regulates the activity of DhNiklp like “on- The group working on elucidating the role off switch”. Their work has provided an of MAP kinase directed phosphatases in Toll- insight into the molecular mechanism of like receptor signaling mediated protective osmosensing by hybrid histidine kinases. Th 1 type immunity at UCS, Kolkata, have Overexpression studies conducted on the for the first time identified that tumor necrosis role of the molecular chaperone protein factor receptor-associated factor (TRAF)3, a DNAJB6 at IISc, Bangalore showed isoform negative regulator of TLR pathway plays a 2 in the cervical cancer cell line Hela critical role in the establishment of visceral increased the rate of cell proliferation, infection. suggesting that it could be involved in the tumor development and progression. Work carried out at NII to understand the role of different domains on the stability of Scientists at IISc Bangalore have reported a interferon-ã induced human guanylate distinct function of FANCO/RAD51C gene binding protein has led to the identification in DNA damage signaling and repair. In of a novel DxEKGD motif in hGBP1. The addition, they have also shown that ATM truncated and mutant proteins showed that and ATR whose mutations are known to both the alpha helix of the intermediate cause ataxia telangiectasia and ATR-seckel region and the motif plays critical role in the syndrome, respectively regulate sister stimulation of the activity which may be chromatid recombination, a process involved related with antiviral activity of the protein.

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Scientists at CCMB working on elucidating Cancer and Tumor Biology the role of inositol pyrophosphates in eukaryotes have shown that yeast lacking Group working on simultaneous inhibition IP7 grow slowly compared to their normal of plasminogen system along with counterpart and attribute their slow growth matrix metalloproteinase in controlling to a decreased role of protein synthesis. angiogenesis at University of Burdwan have Further, the cellular protein synthesis newly synthesized phthalazine compound machinery is reduced in yeast that does not and platinum-azo compound which can be have IP7. The work may help in better used as small molecule inhibitor. understanding of mechanism regulating cell Isoquinilone another compound synthesized growth in all eukaryotes. by the same group could be used as imaging molecules for cancer cells.

(A) (B)

(C) (D)

Fig.4.20: Cancer cell imaging with isoquinilone compound under flurosence microscope. The bright field image [10X objective] of HeLa cells (A) grown in normal culture media and placed on glass slide. The faintly fluorished cells were visible [40X objective], when incubated with only isoquinilone compound (B). The cells were seen to fluorise with greater intensity in presence of increasing amount of FeCl3 (C, D).

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Studies on characterization of functional shown that loss of cell-cell adhesion leads to interaction between estrogen receptor and change in the level of genes that modify the ETS transcription factor in breast cancer cells keratin cytoskeleton. Inhibiting keratin at University of Hyderabad have revealed a expression leads to a decrease in tumor positive co-relative expression of ESE1 with progression and metastasis, while the altered ERα in breast cancer patients and showed cytoskeleton seen in tumor cells leads to an poor patient survival. It is also shown that increase in metastasis and tumor progression. ESE1 expression may lead to ER-negative Therefore modified keratin protein could breast cancer phenotype. Further work is serve as prognostic markers in tumors. being carried out to determine binding regions of these two proteins to design a Developmental Neurobiology peptide which can prevent their interaction. Studies on characterization of topographic Studies on understanding the effect of statin guidance molecules in the visual pathway drugs on breast cancer cells and the at IIT Kanpur, has led to the identification mechanism involved in this process have of candidate molecules that guide the suggested that only hydrophopic statins like ganglion cell axons to their target during fluvastatin, simvastatin selectively cause embryonic development. Further work in breast cancer cell death due to statin induced this area will lead to new regenerative nitric oxide generation via inducible nitric therapeutic strategies for diseases affecting oxide synthase (iNOS). Further, their group the optic nerve. has also shown that statin dysregulate iron transport mechanism in cancer cells and Chemical Biology thereby lead to cancer cell death. Work done at Chittaranjan National Cancer The investigation conducted at BHU has Institute, Kolkata has revealed that demonstrated the role of microwave dopamine can significantly inhibit lung irradiation in the synthesis of novel bioactive tumor growth in-vivo and in-vitro by targeting heterocyclic compounds resulting in a tumor blood vessels and its molecular promising alternative to the existing mechanism has been deciphered. methods of their synthesis.

Studies to investigate control of cell-cell Plant Molecular Biology adhesion and its relevance to metastatic progression at ACTREC, Mumbai have Under the project on development of virus

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resistant papaya crop at Babasaheb Bhimrao The department has taken initiatives to Ambedkar University, Lucknow, SiRNA promote new and emerging areas in modern against two major genes i.e. the coat protein biology and developed a network program gene (AV1) and replicase gene (AC1) of under Systems Biology with focus on papaya leaf curl virus (PaLCuV) have resolving and understanding the regulatory successfully designed. Further work is being dynamics of interaction between Mtb and carried out to design SiRNA against the cellular component of the host using a geminiviral suppressor genes. Under the systems level approach and combining project to understand the molecular basis experimental, theoretical and computational of plant immunity vs. disease at organ level, approach. scientists at NIPGR, New Delhi have developed 2-DE map for nuclear proteome Medical Biotechnology and phosphor-proteome in rice. In chickpea, 2-DE map of ECM proteome has been Infectious Diseases generated and more than 1000 proteins were found to be up regulated upon fungal The Department promoted R&D activities infection. These results might help in in the area of infectious diseases specifically understanding the stress responsive relevant for the Country caused by various proteome and identify target proteins and pathogenic agents including bacteria, strategies to improve stress adaptation in viruses, parasites, fungi and others. plants. Programs were supported to develop preventive, therapeutic and diagnostic tools Vascular Biology for infectious diseases such as Tuberculosis, Cholera, HIV/AIDS, Hepatitis, Influenza, Investigation carried out to elucidate Chikungunya, Malaria, Leishmaniasis etc. signaling mechanism of sFRP4 mediated During the year, 3 task force meetings were inhibition of angiogenesis at Anna organized and 24 new projects were funded. University showed that secreted frizzled Significant achievements of some of the related protein 4 (sFRP4) can inhibit R&D programmes are summarized as below: angiogenesis under both in-vivo and in vitro conditions. The excessive leakiness of Bacterial Diseases endothelial monolayer is coupled with increased ROS levels that promote the Bacterial infections constitute a major cause endothelial cells to undergo apoptosis. of mortality in early infancy in our country.

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In order to improve the efficacy of standard The data provide evidence that ERK-2 antibiotic therapy to reduce neonatal and interacts specifically with Gag present in infant mortality a study was supported to the capsid protein and packaged into virus evaluate the effect of zinc administration as particles. Further studies on the role of ERK- an adjunct to antibiotics in infants with 2 in early activation of NF-κB in early serious bacterial infection. Oral zinc infection are in progress. application has proven to be a promising candidate to improve outcomes of serious Early pregnancy associated protein-1 bacterial illnesses in new-borns and young (Epap-1), isolated from the first trimester infants treated with antibiotics. placental tissue, blood and urine of pregnant women during first trimester has In another study supported, a multiplex been shown to inhibit HIV-1 entry and is PCR based detection kit has been found to have affinity to HIV-1 gp120. A developed, validated and patented for the study was funded to design effective anti- rapid detection of STDs caused by Neisseria HIV peptide from Epap-1. Indeed, small gonorrhoea and Chlamydia trachomatis. Efforts peptides derived from Epap-1 showed were made towards the technology transfer significant anti HIV-1 activity and further for commercialization and development of work to design and develop anti- HIV a cost effective indigenous kit. Under the peptides is in progress. aegis of Infectious Disease area, a LAMP assay has been standardized. The kit was Chandipura virus replicates in nervous shown to be very sensitive for detecting tissue and spreads through the neuron to Neisseria gonorrhoea DNA in preparations reach brain. Also replication of virus in from cultured bacteria, spiked clinical spinal cord induces tissues damages and specimens and real-life clinical specimens. immunological reactions. Study concluded that the death in susceptible young mice Viral Diseases might be due to spinal cord damage and several immunological reactions in nervous A study was supported to define the tissues. Pre-clinical studies with potential mechanism of MAPK/ERK-2 incorporation anti-HIV compound, Acaciaside-B and into HIV and SIV virions and to understand enriched fraction were conducted for their the relationship between MAPK/ERK-2 effects on the several species of vaginal packaging and HIV/SIV replication both in Lactobacillus flora and found to be reasonably the dividing and non-dividing target cells. safe with potent activity.

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Inhibition studies of Influenza A virus another study, Iridoid glucosides are using Ribozyme and siRNA have shown identified as novel inhibitor of that siRNA-ribozyme chimeric constructs Trypanothione reductase from an Indian protect the cells to variable extents against Medicinal Plant Nyctanthes arbortristis. influenza virus infection. Molecular studies Iridoid glucosides were assayed for anti- on host-virus relationships of Swine-flu leishmanial activity with promising (H1N1) and Avian influenza (H5N1) viruses results. have shown that interference using siRNA to the host cell partner protein in the Acaciaside A from Acacia auriculiformis has interaction of viral neuraminidase (NA)- been identified as a novel compound for host cell adhesion molecule-6 (CD66) the control of bancroftian filariasis. caused reduced viral transcription and Acaciaside A is shown to induce apoptosis increased cell apoptosis. Diagnostic tool for in Setaria cervi cells by different pathways dengue infection, a rapid IgM ELISA assay involving up-regulation of different pro- has been developed and validated. A serum apoptotic genes and down-regulation of bank of dengue infected patients has also some of the anti-apoptotic genes. been generated. Clinco-pathological study of arthropathy and acute flaccid paralysis DBT-ICMR Collaboration following Chikungunya virus infection revealed high levels of MCP-1, a chemokine DBT-ICMR collaborative programme on associated with bone degeneration, in “HIV/AIDS and Microbicides” was serum of infected patients. implemented for basic and translational research on immunopathogenesis of HIV Parasitic Diseases and development of therapeutic strategies. It has played an integral role in supporting Studies on novel anti-leishmanial agent the transition of anti-viral candidates from against experimental visceral leishmaniasis early discovery to initial clinical testing. The suggested that chromosome linked nitrone 2nd phase of the programme has been can function as an important immuno- announced aiming at accelerating research modulator even in an immune- that will generate knowledge and develop compromised state. The data suggest that state-of-the-art technologies to provide the chromosome- linked nitrones are the class basis for the development of HIV vaccines of compounds with potential for further and novel therapies against HIV including development for anti-protozoal therapy. In microbicides.

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HIV/AIDS participants have registered at website to provide a list of reagents and antibodies In order to neutralize diverse HIV isolates, available with them. Various institutes have E coli expressed Outer Domain based developed protocols, assays, cell lines from immunogen (ODEC) has been shown to be peripheral blood mononuclear cells, highly immunogenic which resulted in complex mobility analysis, biological neutralization of B and C subtypes. Similarly isolation of HIV from semen of HIV-infected CD4Bs, a gp120 based fragment, was found individuals, purification of Tat protein and to elicit better neutralization than gp120. its functional aspects. Attempts are being made towards patenting the CD4Bs immunogens. Microbicides

Indian clade C envelop chain isolated from Several chemically synthesized reverse recently transmitted HIV-1 showed moderate transcriptase inhibitors have shown potential sensitivities to variety of antibodies to develop as anti-HIV molecules. Recently including broadly neutralizing monoclonal identified Rabbit epididymal haemoglobin antibodies. Novel residues in clade C HIV- beta peptide (REHbβP) with antimicrobial/ 1 Env were found to confer enhanced virus anti HIV-1 properties has been filed for neutralization by acting on different sites patenting. Compounds from different plants on Env. A new class of specific and tight sources exhibited promising anti-HIV binders that inhibit Rev-RRE interaction in activity. BASANT, a polyherbal gel, used HIV were synthesized. A novel dual reporter as a vaginal microbicide showed promising based single step assay system has been results in terms of safety and acceptability developed for evaluation of drugs that among women in phase-1 clinical trial. inhibit Rev-RRE and Tat-TAR interactions Potential anti-HIV compounds from various that can lead to development of inhibitors plant extracts have been identified using of HIV replication. Novel nucleobase ethers various standardized assays in vitro at NII, such as glycol and propylene glycol New Delhi. neucleobase ethers that bind with bulge and loop region of TAR RNA have been DBT-IAVI Collaboration synthesized. The collaborative programme has been A Virtual Knowledge and Resource Centre further extended for another period of 5 is functional at NARI, Pune. Fifty eight years under the aegis of Indian Medicinal

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Chemistry Programme. Two projects drug-interventions, biomarkers etc. The have been funded at ICGEB, New Delhi Curcumin clinical trials in cancer have to study the development of reached a critical stage. DBT had set-up a conformationally preferred peptide “Curcumin Clinical Pharmacology Lab” at immunogens as candidates against HIV- ACTREC, Mumbai for pharma-cological infection. The emphasis is on designing assessment of Curcumin & its metabolites in peptide immunogens to elicit HIV-1 serum/plasma of patients on Curcumin neutralizing monoclonal antibodies. At intervention. The first lot of analysis has been IISc, Bangalore the study is directed done. The trials on oral-pre-cancer lesions towards designing and characterization of have been completed and several meetings novel Outer Domain (OD) derived of the Data Safety Monitoring Board taken immunogens with additional mutations to place to firm up SAP. The data captured prevent protein aggregation. and cleaning is going on.

Chronic Disease Biology A Cancer Data been has been created by IOB, Bangalore which encompasses all There is a greater emphasis on the chronic important and relevant information about disease area. There are about 120 ongoing DBT’s stake in the cancer domain. It can be projects in the area covering patho-biolgical accessed though http://www.incredb.org/ aspects of various cancer, pathway discovery, dbt_home.html.

Fig. 4.21: Indian Cancer Research Database

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Neuroscience amongst school going children. The Department is also planning to invite The DBT had established an Expert Group proposals in the area of Diabetes soon. on Neurobiology under its Task force on Chronic Disease Biology (EGN-CDB). The Up-gradation of Infrastructure in Medical EGN-CDB is making efforts to put more Colleges in the NER thrust in the area of Neurosciences research in the country, with its call for proposals, The DBT program on Development/Up- advertised in the April, 2010 followed by a gradation of Infrastructure in Medical fresh RFA in September, 2011. More than Colleges in the NER was started in the year 100 projects have been funded covering 2009. The program is now operational in 12 various aspects of neuroscience. A dedicated medical colleges/ institutions in four states website for neuro-projects has been of the Region, namely Assam, Nagaland, prepared; and relevant information Tripura and Manipur. Labs of 21 Principal pertaining to DBT’s activities in neuro-area Investigators have been renovated / is available at dbt-neuro.ncbs.res.in hosted upgraded for carrying out quality research by NCBS, Bangaluru. on various health problems prevalent in the region using modern biotechnology tools Endocrine, Cardiac, Autoimmune Diseases and technologies. Various scientific & Reproductive Biology equipments including 27 high cost equipments such as flow cytometer, Real- A strategy meeting was held to provide Time PCR machine, Hi-speed centrifuges, - more impetus to the area of “Endocrine, 80 freezers etc. have been procured and Cardiac, Renal, Autoimmune Diseases & being installed. Several of these labs are Reproductive Biology” under Chronic now ready for formal inauguration. Disease Biology. Call for Proposals for Kidney Diseases and Autoimmune Nephrotic Syndrome Disorders were released during the year and about 40 projects shortlisted for final round The Department has funded a project to of examination. A brain-storming on explore the pathogenesis of idiopathic Rheumatic heart disease was held. The nephrotic syndrome of childhood. Leads general consensus was that despite a belief from this study are likely to provide that RHD is not a disease of public health evidence for cytokine polarization of T- concern; the prevalence rate was high helper cells. On the long-term, this study

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might contribute to discovery of a biomarker Technology Institute (THSTI) and for the Nephrotic Syndrome disease course. International AIDS Vaccine Initiative (IAVI) to accelerate the HIV Vaccine discovery Hemolytic Uremic Syndrome program. The program is targeted to expand the number of vaccine candidates globally A project was pursued to determine the for testing, and development. The programme presence of autoantibodies against factor H shall engage scientists, build scientific in Indian children with Hemolytic Uremic capacity in India towards enhancement of Syndrome and their relation to disease severity global R&D efforts for HIV vaccine and course and to characterize the antibodies development, strengthen efforts to share and devise better treatments for the future. commercialize scientific knowledge and foster inclusive innovation process. The unique Celiac Disease Project on Diagnostics industrial-type high-throughput vaccine design, screening and selection processes A project on towards the development of a proposed for the THSTI-IAVI HIV Vaccine rapid, indigenous test for diagnosis of celiac Lab will be largely facilitated by disease was undertaken and an ELISA KIT interdisciplinary interaction driven by the has been developed. The Kit has been tested principles of international collaboration, high- against well-characterized sera samples and quality science and vaccine-oriented research. also on sera collected from children diagnosed with celiac diseases. The samples Biotechnology Strategic Planning and tested and compared with other commercially Analysis Centre (Bio-SPACe) available ELISA kits and the Kit is found comparable with the best imported Kit The Department has supported this centre available in the market and is ready for with a DBT-ICGEB collaborative effort with commercialization. Development of Dip-stick the primary emphasis to address issues that would contain all the three antibodies related to healthcare biotechnology, perform (IgA, IgM, IgG) for detection in fresh human technology assessment in order to bring out blood samples progressing well. appropriate strategic plans relevant for the country. In addition the centre would take Vaccine Research and Development up work on evaluation of intended efficacy of new technologies which could range from The Department has taken collaborative effort disease burdens of neglected diseases, newly between Translational Health Science and diagnosable chronic ailments, likely future

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impact of drug resistant diseases, increased (ATPC) is supported to promote incidence of diseases due to climate change, multidisciplinary research that translates faster industrialization and lifestyle changes scientific and technological advancements such as diabetes, cancer, and respiratory into innovations towards improvement of diseases. public health. It would act as a catalyst for multidisciplinary basic and translational Biomedical Genomics Centre at IPGMER, R&D by providing relevant state of the art Kolkata (BMGC-K) instrumentation, and professional services for research laboratories at the Biotech The Department has also supported BMGC- Science Cluster (BSC) Faridabad, viz. K at Kolkata with “precisely defined” on Regional Centre for Biotechnology (RCB), disease phenotypes, including events Translational Health Science & Technology resulting from administration of relevant Institute (THSTI) etc. In addition, it would drugs, drawn from the patient population also promote industry-academia of the Medical School and to return back to participation and training of personnel at the patients with genomic solutions for different levels. improved diagnosis, management and prophylaxis. This centre will act as a Stem Cell Research platform for clinical scientists to carry out research in genomics. In addition, it also The Department is promoting basic and undertakes various events viz. workshops translational research in the area of stem and CME courses on biomedical genomics, cells and regenerative medicine in the with the eventual goal of initiating a DM/ country since 2001 keeping in view its DNB programme on Medical/Clinical potential therapeutic applications. A Genetics and impart clinical services for number of programmes on various aspects detection of genetic disorders and their of embryonic and induced pluripotent stem management, thus BMGC-K will foster cells have been implemented for basic and capacity-building that is sorely lacking in clinical research using adult stem cells. medical profession at present. Currently, over 45 institutions, hospitals and industry are involved in stem cell Advanced Technology Platform Centre research in the country. An institute for (ATPC), Faridabad Stem Cell Biology and Regenerative Medicine has been established at Bangalore An advanced Technology Platform Centre with its translational units at Christian

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Medical College, Vellore. GMP and clean cells; differentiation of human mesenchymal room facilities have been established in stem cells to cardiomyocytic and adipocytic various medical schools. The Centre at lineage in-vitro; AAV-based vector Vellore is a dedicated Center for technology on induced pluripotent stem translational stem cell research in a medical cells, etc. In addition to R&D programmes, environment established within an training programmes and workshop on academic medical environment with several iPSCs have also been supported during the basic and clinical (physician) scientists year. Programmes have been formulated in involved in stem cell research. Three young the area of adult stem cells and sanctioned scientists were sent for long training on for implementation. DBT overseas scheme in top laboratories in USA for specific areas of application to Clinical Research be developed at Centre. The work involves: AAV based gene therapy, The Department has implemented multi- endothelial progenitors de novo and iPS centric, multi-investigators clinical trials in derived in MGH, studies on the the areas of acute myocardial infarction hematopoietic stem cell niche. (AMI), acute ischemic stroke (AIS) and critical limb ischemia using autologous Embryonic and induced pluripotent Stem bone marrow adult stem cells. Recruitment Cells of 250 patients (125 control group and 125 intervention group) in AMI clinical trial Embryonic stem cell lines generated from and 120 patients (60 control group and 60 discarded grade III blastocysts at JNCASR, intervention group) in AIS clinical trial Bangalore and deposited in the UK stem have been completed. A clinical trial cell bank are being used by the national proposal has been implemented to assess and international scientists for research safety and efficacy of adult autologous purposes. During the period, a number of peripheral blood cells in critical limb programmes have been generated and ischemia. Patients are being recruited at implemented on various aspects of four hospitals in the country. The sample embryonic stem cells and induced size of the study is 200 (100 in the pluripotent stem cells (iPSCs). Some of intervention arm and 100 in the Control the programmes are: generation and arm). Follow-up of the recruited patients characterization of iPSCs; analysis of human under this study is being carried out by amniotic membrane mesenchymal stem all the participating centres.

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Guidelines for Stem Cell Research and by the Department. Significant Therapy achievements of some of the projects are presented below: In order to revise the guidelines for stem cell research and therapy formulated jointly Bio-imaging/Instrumentation by the Department and Indian Council of Medical Research (ICMR), public Scientists at IIT Kharagpur are aiming to consultation in northern region were investigate the biomechanical factors organized in December 2011. The inputs/ responsible for loosening and eventual opinion received from all the stakeholders failure of an implant, using numerical during public consultation organized in east, (Finite Element Analysis), and west, south, north-east and northern regions experimental techniques. The primary goal will be taken into account during revision of the project is to develop better of the guidelines. orthopaedic implants. The study is mainly focused on lower limbs, like the hip and Bioengineering the knee joint replacements. This study sought to explain the relationship between Bioengineering is a fusion of engineering load transfer and some biomechanical sciences with life sciences for promotion failure mechanisms in femoral head of scientific discovery and the development resurfacing, using FE analysis and of new biomedical technologies and experimental measurements, in order to therapies through research and education. suggest measures for improved femoral Under this scheme, the Department has laid resurfacing implant. emphasis to develop bio-based technology involving interdisciplinary sciences Scientists at BITS, Pilani are making effort towards development of novel materials, to develop a novel microscopic technique designing new devices, establishing new based on photothermal detection of metallic methods for disease diagnosis, developing nanoparticle labels. The “photothermal new computational approaches to create microscope” contributes to the area of biological system etc. During this period biomolecular imaging and tracking. The the Department received 160 proposals out study would provide insight on transport of which 25 proposals were found worthy mechanisms of DNA through the nuclear of financial support and 60 proposals are pore complexes and its internalisation in under processing for further consideration the nucleus, with potential implications in

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gene therapy. Gold nanoparticles are targeting into in vitro virus cell culture detected by sensing intensity changes of the system. Peptides having rabies virus probe beam using a Lock in amplifier. glycoprotein motif with NLS sequence have Labeling of DNA is done with different dye been designed and their delivery are seen molecules and gold nanoparticles. Once the in nerve cell (N2a cell line) to develop detection scheme is optimized to detect and tissue specific novel peptides for targeting image gold nanoparticle labeled PNA particularly CNS across BBB. The biomolecules, it will provide a novel investigators found that PNA uptake is microscopic technique free of photo significantly higher in N2a cells and in bleaching. primary cells of mouse brain in comparison to primary cells of liver, spleen and kidney. Scientists at IIT Kanpur have developed a The identified peptides as molecular mechanistic model for predicting growth of steerings for brain homing along with aneurysms in an arterial bifurcation. The efficacy of PNA as antiviral are underway investigators have developed a numerical for the in vivo studies. simulator for oscillatory flow in arterial bifurcation. Simulations have been carried Scientists at IIT Madras are in the process out with the following features a.) adaptive of investigating simultaneous release of high quality mesh generation for FVM antibiotics and anti-inflammatory drugs calculations, b.) computational fluid using CDHA nanocarriers. CDHA dynamics calculations over unstructured nanocarriers of diferent Ca/P ratios are meshes, c.) data analysis, extraction of synthesized and characterized. The loading physiologically meaningful parameters and and release profiles of two drugs, an d.) tools for visualization of the results. antibiotic tetracycline and anti- inflammatory drug ibuprofen have been Biomaterial studied along-with doxycycline and cefalexin. The nanocarriers exhibit both Scientists at IVRI, Izzatnagar have single and two stage release profiles of developed novel intelligent peptides for doxycycline depending on the Ca/P ratio targeting PNA into cell and see their of CDHA. antiviral efficacy to develop non-invasive antisense therapeutic intervention. They Tissue Engineering designed and synthesized PNA for fusion F-gene of NDV and evaluated them by Scientists at IIT Kanpur and ILBS, New Delhi

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aims at developing a liver assist device for embryonic fibroblasts are seeded on the the temporary treatment of patients with acellular dermal matrix scaffold and 3D acute and acute on chronic liver failure. The growth of cells has been observed. The treatment with this device may help bridge histological and scanning electron the acute crisis and help spontaneous microscopic examinations have been hepatic regeneration. The anticipated performed for the morphological assessment product will be a suitable polymeric of cellular growth on biomaterials. The cell bioreactor immobilized with appropriate seeded 3D biomaterials would be used for hepatocytes and cryopreserved for ready reconstructive surgical applications in the application. A suitable polymer based on experimental animal models, wherein the poly (N-isopropylacrylamide) and chitosan wounds will be created in the laboratory have been synthesized as cryogel scaffold. animals and will be implanted with cell Bioreactor models in the form of cryogel seeded biomaterials for achieving early sheets have been fabricated. Detailed healing. analysis and physico-chemical characterisation of the cryogels based on a Scientists at Amrita Centre for Nanosciences number of parameters have been carried aimed to develop alginate, chitin and out to establish swelling kinetics, porosity, chitosan bandages based on hydrogels with flow rate, protein diffusion and absorption. non-toxic ZnO/Herb Hemigraphis Ulternata Efforts at identification and optimisation of nanoformulations for wound dressing cell lines as potential sources for the applications. The investigators developed Bioreactor are in progress. flexible and microporous chitosan hydrogel/ nano zinc oxide composite bandage (CZB) Scientists at IVRI Izzatnagar, are working by the incorporation of zinc oxide on the development of 3-D acellular dermal nanoparticles (nZnO) into chitosan hydrogel. matrices for reconstructive surgery and The prepared nanocomposite bandages have evaluate the surgical potential and efficacy been characterized and properties like of 3-D matrices in laboratory animal models. swelling, degradation, blood clotting, Different protocols for de-epithelization have antibacterial, cytocompatibility, cell been optimized in rabbit, goat, pig and rat. attachment and infiltration ability of the The in vitro cultured primary chicken prepared nanocomposite bandages are been embryonic fibroblasts and primary mouse evaluated.

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Fig. 4.22: The nanocomposite bandage showed enhanced swelling, blood clotting and antibacterial activity. The study strongly encourages the use of these CZBs for burn, chronic and diabetic wound infections.

Biosensor complete match as well as single base mismatch detection, compared to DNA. It Scientists at IACS, Kolkata developed a has been found that the LNA-based DNA sensitive and robust cantilever nanosensor detection exhibits the highest sensitivity in for genomic research. The study envisages single base mismatch discrimination. the systematic development of films of alternative nucleic acids, e.g., the peptide Scientists at IIT Kharagpur are designing a nucleic acid (PNA) and locked nucleic acid digital and plug-based microfluidic system (LNA)], onto a solid substrate and to study the aggregation kinetics of the â- assessment of DNA detection capabilities amyloid peptide in presence of electric field, of these layers in comparison to a DNA chemical molecules and metal ions. The film. The investigators have optimized the investigators made i) plug based studies in ordered arrangement and the most upright microchannels and ii) droplet based digital molecular configuration as per requirements microfluidic systems towards the of an effective biosensor surface. It is found development of microfluidic systems. The that such a layer is capable of much superior microchannels are fabricated by standard DNA detection capability in terms of soft lithographic technique.

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Fig. 4.23 : (a) Schematic of the experiment used to investigate the diffusive broadening in laminar ûow of ctDNA and EtBr. (b) The concentration of the fluorescent product was plotted as a function of both y and x direction, indicating enhanced diffusive mixing and product formation along the length of the microchannel.

Digital microfluidics utilizing electro-wetting- Major projects have been initiated involving on-dielectric (EWOD) has been developed to clinicians, molecular geneticists and handle and manipulate discrete droplets anthropologists. India’s rich genetic resource rather than a continuous stream. is being utilized to develop baseline data on various ethnic groups for disease susceptibility and provide genetic services to large number of families including prenatal diagnosis and counseling to affected families including tribal population and awareness among public regarding prevalence of common genetic disorders in the country like thalassemia, DMD, SCD, haemophilia etc. The department has focused on disease based human genome analysis program by setting up genetic Fig. 4.24: Droplet based digital microfluidic platform clinics. Anticipating that the HGP data will be available in public domain, DBT is Human Genetics and Genome prudently using its funds to initiate project Analysis with major relevance in post genome era. With this in view, major infrastructure has The Human Genetics and Genome Analysis been established at various institutions to programme that was initiated two decades undertake advanced genome research ago has revolutionized research in the field. including sequencing projects.

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Significant achievements made under genitalia. Genotype analysis led to the R&D projects identification of mutations indicating that the patients had abnormal genotype. Further At M. S. University of Baroda, work on the mutation varied with the type of CAH analysis of possible genotype - phenotype in patients. correlation between oxidative stress related genes polymorphisms and Vitiligo was At CDFD, Hyderabad the group funded. The study revealed a significant standardized the process of transformation increase in SOD1 and SOD2 activities of human lymphocytes using Epstein Barr concurrent with a significant decrease in virus obtained from B-95 marmoset cell line CAT, GPX1 and G6PDH activities in vitiligo and revival of frozen cell lines. In addition patients as compared to controls. The GPX1 the group were able to establish cell lines T/C exon 1 (Leu6Pro; rs4991448) and G6PD from 8 patients with rare genetic disorders G/C exon 2 (Gln41His; rs1050827) SNPs with future plan to establish more cell lines were significantly associated with vitiligo. from additional patients with rare genetic Study at University of Hyderabad diseases. demonstrated for the first time show that PfMre11 is an authentic DNA repair protein Under the project study on “Sperm Factors of the protozoan parasite Plasmodium (DNA damage, mt mutations, oxidative falciparum. Lack of sequence identity stress) - Role in Recurrent spontaneous between PfMre11 and human Mre11 abortion (RSA)” at D/o Anatomy, 30 indicates that this DNA repair protein is a idiopathic RSA cases showed the association promising candidate for chemotherapeutic of increased ROS level and DFI. Along with intervention. ROS study the DFI in such cases was also found to be higher in comparison to controls Under a project on Congenital Adrenal and the study concluded that male factor Hyperplasia (CGA) implemented at AIIMS, especially paternal DNA, do play a role in New Delhi, 49 patients were diagnosed to embryonic and fetal development and loss have SV CAH type, 12 patients were of DNA integrity may lead to RSA. diagnosed to have SW CAH type and 2 were diagnosed to have non classic type of In a project on “Biochemical and Functional CAH as per their clinical and hormonal Characterization of RIO kinase(s) from profile. Among these sixty three CAH Plasmodium falciparum as Potential Drug patients, fifty six (88.89%) had ambiguous Target” at IIT, Guwahati, 3-D model of the

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PFD0975w was prepared and critical amino the details of the all clinical samples was acids for kinase activity and auto- created. Other databases have been created phosphorylation were identified. The group to document clinical and consumption cloned PFD0975w from Plasmodium falciparum details of clinical samples, as well as the to over-express the protein in E.coli. Efforts experimental details of the proteomic study. to design high resolution horizontal PAGE for non-radioactive protein kinase assays are Under the project on End Stage Renal underway. Disease (ESRD) at SGPGIMS, Lucknow, the group collected 368 patients and their At ILBS, Delhi studies were undertaken on donors who have reported for the Ist cross “Early prediction of interferon match with this group, and also collected responsiveness in patients infected with 400 unrelated individuals from that region Hepatitis C virus (HCV) using of UP to study the population stratification. pharmacogenomic tools”. Patients have been Standardization of protocols and population enrolled for interferon induced gene stratification was done with the aim to start expression analysis and HCV RNA detection the patient and donor KIR genotyping and before and after IFN therapy was done. The get more insight into the molecular profiling response rate to IFN therapy in HCV infected of KIR and their clinical relevance to the genotype1 patients was 55-60%, while in end stage renal disease (ESRD) and graft genotype 3 patients it was 90%. Further the function after renal transplantation. group selected 36 genes for gene expression profile based on interferon signaling and Under project on construction of genomic other related pathway. Analysis of these library of Leptospira interrogans serovar gene showed an altered gene expression Autumnalis for the identification of profile of IFN-induced genes, cytokines immunogenicproteins and development of (interleukins), SOCS, apoptotic and other DNA vaccine, the group at Bharathidasan related gene in the HCV infected follow up University constructed and screened the patients on PBMCs at day 0, 1, 4, 7, 14, 28 phage library and identified two clones that and at weeks 8, 12, 24. have showed good sensitivity and specificity and are expected to be an immunogenic At IIT, Mumbai under the study on gene plays a vital role during infection. proteomic analysis of human gliomas for biomarker discovery database entitled At MAMC, Delhi, group working on “TMH Hospital’s Patient Database” to store lysosomal storage disorders project study,

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standardize the gaucher enzyme assay and Health (NIH), USA. DBT implemented major Mucopolysaccharidoses (MPSI) on dried blood programme on Oral Cancer, most prevalent spot using fluoroimmuno assay. This recently form of cancer in India, at National Institute gained expertise will help centres in remote of Biomedical Genomics (NIBMG), Kalyani, areas to send samples to lab on filter paper in collaboration with Advanced Centre for and the gaucher disease can be diagnosed. Research, Treatment and Education on The group has also done the detection of Cancer (ACTREC), Mumbai. So far, whole- beta- Glucosidase enzyme for gaucher disease exome data on 34 pairs of patient samples and Alpha-L-iduronidase enzyme for MPS I has been generated. The analysis of 30 pairs on dried blood spots first time in India using of samples has been completed and all the Fluroimmunoassay system and have inherited (germline) and acquired (somatic) been cross checked by Traditional genomic alterations in the samples have Fluroassaytechniquies. The current technique been catalogued. is much more accurate and sensitive showing strong correlation co-efficient (R2) indicating Environmental Biotechnology excellent ability to differentiate between healthy controls and affected. Environmental biotechnology research and development programme are focused on the International Cancer Genome development and use of biotechnological Consortium (ICGC) Programme tools for management of environment and biodiversity conservation. The main focus India is a part of Human Cancer Genome was given on development of mitigation Project – an International Collaborative technologies for Climate Change, microbial Initiative (TCGA)” launched in November, technologies for environmental 2008 with commitments of eight countries improvement, treatment process of i.e. India, Australia, Canada, China, France, industrial effluent, bioremediation of Japan, Spain and United Kingdom alongwith xenobiotic compounds, biodiversity eleven funding organizations to generate conservation and characterization of comprehensive, high-resolution analyses of biodiversity. Efforts were made for the genomic changes for 8 forms of cancer treatment of wastes and abatement of found across the planet based on the pollution through bioremediation. Studies International Cancer Genome Atlas on microbial diversity of various programme implemented by National environments and their genetic information Cancer Institute of National Institute of were carried out for isolating micro-

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organisms that could be used in the mercury bioremediation demonstrated the manufacture of enzymes and a wide range feasibility of manganese bioremediation and of bioactive compounds, as well as in simultaneous manganese oxide nanoparticle bioremediation processes. DBT has taken synthesis by Bacillus sp. cells. The up several initiatives and continued its synthesized nanoparticles were characterized support in various ongoing projects. as orthorhombic MnO2 with average size of 4.62 ± 0.14 nm. Manganese oxide Bioremediation/Biodegradation nanoparticles could also be synthesized ex- situ by the cell lysate. In a project implemented by TERI, New Delhi a pilot scale facility of bioreactor with Delhi University conducted a study on working volume of 1000 liter has been isolation of bacteria capable of degrading established at Gualpahari with an up scaling endosulfan from soil using selective facility for bulk production of Oil-zapper. enrichment technique. Achromobacter Total 600 tonnes of oil zapper was supplied xylosoxidans strain C8B was able to degrade to oil companies. Bioremediation of oil endosulfan sulfate, which is highly persistent contaminated soil in operation area of and toxic metabolite of Endosulfan. ONGC, IOCL, BPCL and HPCL is completed and the sites have been restored after At Bharthidasan University, Thiruchirapalli bioremediation. work on identification and evaluation of novel microbes in CETP of Tannery At IGIB and CPPRI, Saharanpur, technology industrial units through molecular approach for improvement of a process of biological was carried out. Bacterial diversity in the reduction of AOX, colour, COD and BOD effluent were analyzed through 16S rRNA of waste water emanated from large pulp & amplification and sequence results revealed paper industries was developed. The the dominance of firmicutes and the microbial consortium could bring down the dominant genus is Bacillus, with variable colour upto 82% and lignin upto 76% species diversity. Notably, putative Bacillus besides reducing COD and BOD within the sp, B. firmus and B. licheniformis were permissible limits. observed in all stages of treatment. These species might have the capability to degrade At IIT, Delhi study undertaken on the complex tannin into simpler sub immobilization of heavy metals derivatives. Metagenomic DNA isolated bioaccumulating microbial strains for from effluent and 16S rRNA gene was

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amplified. Future course of action is to At IIT, Mumbai in a study on development prepare 16S library of non-culture microbes of a structured model and experimental and screen the novel tannase gene from the validation for the prediction of the kinetics micro biome CETP. of competitive metabolic networks in hydrocarbon degrading organisms, the At SPU, Vallabh Vidyanagar and IICT, substrate uptake pattern of the model Hyderabad, studies were undertaken jointly organism Pseudomonas putida CSV86 was on application of periodic discontinuous studied. This organism preferentially utilizes batch operation to enhance treatment aromatics over glucose and co-metabolizes efficiency of dye containing wastewater. Two them with organic acids. The strains showed distinct consortia optimized for their simultaneous utilization of organic acids and physico-chemical parameters revealed that aromatic compounds. A cybernetic model to at higher salt concentration also these predict the growth and substrate uptake of consortia were able to degrade dye. Reactor P.putida CSV86 was developed. operation was carried out using simulated textile effluent containing nine different Biodegradable Plastic/ Biopolymer dyes (monoazo, diazo and triazo) and reactor efficiency checked for various shock In a multicentric project implemented by loadings found that consortium sustained Osmania University, Hyderabad, IIT, up to 500 mg/l dye concentration at two Kharagpur and NIIST, Trivandrum, studies days retention time. Biochemical and on cost effective production of lactic acid electrochemical analysis showed basic for Polylactide (PLA) synthesis and understanding on the functional role of biodegradation was carried out. A total of aerobic microenvironment in dye removal. fifteen agricultural and industrial wastes are screened for checking their potential to At IIT, Delhi laccase mediated degradation replace the refined sugars for cost effective of textile dyes and textile wastewater was production of lactic acid. Scaling up of lactic investigated. The process was developed in acid fermentation by Lactobacillus amylophilus an enzyme membrane reactor using both GV6 with the optimized media composition batch and continuous methods. Degradation was carried out. New bioreactor trial at IIT, pathways were established for three Kharagpur showed promising results. commonly used dyes. Mechanism of action Newly isolated indigenous cultures for PLA of laccase on complex triarylmethane dyes degradation were developed at NIIST, was shown. Trivandrum.

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At ARI and NCL Pune, studies on characterized. TTHADH stereo development of blends and composites specifically coverts glycerol into D- based on biodegradable polymer of glyceraldehyde, a chiral molecule. microbial origin viz. PHA was carried out. Process optimization for producing The production of the biopolymer was monoglyceride from glycerol was carried optimized from using Halomonas campisalis out. strain in 14 L SS fermenter. PHA could be produced from cheap substrates like baggase In another study on development of a extract and table sugar with significant bioprocess for the production of reduction in cost of production. Scale up Polyhydroxy Butyrate (PHB) from bio-diesel production of PHA carried out in 120 L SS industry generated glycerol, bacterial strains fermenter with 85 L production medium were screened for PHB production. Among resulted in 26 g PHA. The developed PHA these strains Bacillus firmus NII 0830 was was found to be biodegradable as per found to be a good producer of PHB. ASTM methods. The blends and Optimization of different process parameters nanocomposites of PHBV with nanoactive were carried out to enhance the PHB Al2O3, Optim, Nylon 11 and production. The result showed that Hydroxyapetite were successfully prepared phosphate limited condition was more which show desired performance in terms favorable for PHB accumulation by Bacillus of mechanical properties. The suitability of firmus. PHBV – Optim blend for the cellular growth has been studied. In a project on sustainable utilization of trash fish for the formulation of various Product from Waste valuable products, implemented by Annamalai University, TN, investigations At IIT Delhi, biotechnological approaches lead to the production of Fish oil, Chitin for utilization of Jatropha curcsa oil cake and Chitosan, Fish Protein Concentrate (FPC), and glycerol for obtaining value added Fish Meal, Fish Pellet feed, Fish Bone products were explored. Two specific Powder (calcium powder), Fish Collagen isoinhibitors for trypsin have been form various low value as well as trash/ isolated and purified from deoiled bycatch fishes. The products developed out Jatropha curcas meal. A new alcohol of this project were periodically for its dehydrogenase from Thermus thermophilus proximate composition, microbial status, (TTHADH) was isolated, purified and shelf life etc.

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Environmental Metagenomics These clones have been checked for antibiotic production against different At MKU, Madurai, microbial diversity on pathogens such as Vibrio cholera and X. goat skin surface was assessed by 16S oryzae. rRNA gene amplification and sequence comparison. Unique sequences that shared At UDSC, New Delhi a protocol was sequences similarity with unculturable developed for maximizing the extraction of bacteria were submitted to the public DNA from the environmental samples that database. A metagenomic DNA library allows the extraction of humic acid free with 70,000 recombinant clones were DNA in one-step. Metagenomic libraries constructed and screened for clones have been constructed and the clones have exhibiting proteases activity. A novel been screened for xylanolytic activity. The alkaline serine protease with optimal xylanase gene was expressed and the activity at pH 10.5 was identified, purified enzyme was purified. Enzyme variants have and characterized. By PCR based screening been generated by site-directed mutagenesis two antibacterial protein coding genes and directed evolution, and these are being tmp1 and tmp3 were identified. The analyzed. inhibitory spectrum of Tmp1 was enhanced by random mutagenesis and site- At BHU, Varanasi, work on bio-prospecting directed mutagenesis. The site of action of novel genes from the metagenome of coal and 3D structure of Tmp3 were confirmed beds for the biotransformation of lignite coal by fluorescent microscopy, CD and NMR into high efficiency fuels is being carried spectroscopy. Identified alkaline protease out. Coal bed metagenome was analyzed could be considered for its applicability by extracting metagenomic DNA from the in detergent industries. Synthetic water samples collected from 800m depth derivatives of Tmp1 and Tmp3 could be of Jharia coal mines. The bacterial considered for therapeutic applications. community was dominated by the members of Azonexus, Azospira, Dechloromonas and At IARI, New Delhi studies undertaken to Thiobacillus. A plasmid and a fosmid library assess the genetic and biochemical potential was also prepared from the coalbed of soil microorganisms by culture- metagenome. Nucleotide sequence of some independent methods, a 781-member fosmid of the plasmids/fosmids was determined library in Escherichia coli with DNA extracted and some potentially useful genes were directly from soil has been constructed. identified.

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At IIT, Mumbai, search was made for novel At NEERI, Nagpur, mining the metagenome pathways, enzymes or operons involved in of activated biomass for new antibiotic the degradation of aromatic compounds using molecules, culture based screening for metagenomic approach, the gene for antibiotics yielded two isolates that show terephthalare dioxygenase oxygenase antimicrobial properties against, E.coli, component was amplified from Pseudomonas Salmonella, Bacillus and multi-drug resistant aeroginosa strain PP4 and Pseudomonas sp. strain Enterobacter. The isolates have been PPD. The gene was used as a probe for identified by 16S rDNA sequence analysis screening the metagenomic library. The gene as Alcaligenes sp. and Pandorea sp. The encoding the enzyme like salicylate 5- anitimicrobial agent has been identified as hydroxylase and conserved cupin-2 region of Phenol 2,6-bis(1,1 dimethylethyl). Screening gentisate 1,2-dioxyganase were amplified from the metagenome has yielded one clone the naphthalene degrading strain in the library. demonstrating antimicrobial activity against Serratia. Sequence homology demonstrates At NIIST, Trivandrum, work on construction similarity to Lasso peptide and Polyketide and screening of environmental DNA Synthase I, both reported antimicrobial libraries for novel beta- lactamase inhibitors agents. and lipases was carried out. Soil metagenomic library undertaken from Biodiversity Conservation Studies Western Ghats of Kerala was screened for lipase, protease, amylase and b-lactamase Animal Biodiversity inhibitors. Eighteen clones positive for lipase, eleven clones positive for amylase At CCMB, Hyderabad work on estimation and thirteen clones positive for protease studies of wild tigers in tiger reserves in were obtained. Partial purification and India by DNA profiling of faecal samples characterization of amylase and lipase were has been carried out. The protocols for scat carried out. Esterase form clones were sample collections were established to obtain temperature stable (800C), solvent tolerant maximum DNA, to minimize losses during (up to 25% methanol) and halo tolerant (up preservation and to quantifying and grade to 2M NaCl) and these properties make DNA extracts. Ten tetranucleotide and four them very unique and highly desirable for dinucleotide microsatellite markers for industrial application including trans genotyping individual tigers have been esterifcation reactions for biodiesel selected and screened. Protocols for two- production and in organic synthesis. step PCR and genotyping have been

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standardized to get accurate results with presence of several novel species of bacteria minimal amounts of DNA and to ascertain and archaea. the impact of habitat fragmentation, hostile landscapes with human presence on tiger Plant Biodiversity presence and their movements. At Annamalai University, TN conservation At MKU, Madurai, molecular systematics and genetic variations of three RET and population genetics studies of lesser mangrove species (xylocarpus mekongensis, dog faced fruit bat Cynopterus brachyotis have xylocarpus granatum and excoecaria agallocha) been carried out. Studies show that of Pichavaram mangroves, Tamil Nadu were morphological keys are insufficient to studied. Micropropagation protocol was identify individuals of both species at high standardized for Excoecaria agallocha and altitudes and areas of cohabitation. Many standardization is under progress with mophovariants may be taxonomically Xylocarpus species. The plants propagated unique. Hill population of C. sphinx in through seeds, vegetative and Southern India was isolated and the micropropagation have been hardened and occurance of C. sphinx in high altitudes reintroduced in the natural mangrove forest above 1000m was also reported. and in the degraded area where afforestation is continuing in Pichavaram. The Microbial Biodiversity establishments of the seedlings are around 82% with Excoecaria agallocha, 72% with X. At ARI, Pune archaeal biodiversity from granatum and 40% with X. moluccensis. Indian Archipelago have been studied using molecular pylogenetic approach to At Goa University, Goa studies on document the microbial diversity (bacterial taxonomy, populations, environment, and archaeal) associated with mud volcanoes ecology, propagation, introduction and of Andaman Islands. These mud volcanoes genetic diversity of Phyllanthus talbotii and erupted recently after the earthquake Pseudoglochidion anamalayanum have been leading to Tsunami disaster of 2004. The carried out. ITS sequence shows that the data reported describes the account of the genus Pseudoglochidion can be subsumed microbial diversity of the mud volcano under the genus Phyllanthus; Phyllanthus evaluated by culture independent talbotii is releated to Phyllanthus cinereus of technique. This investigation based on 16s Srilanka. Five new populations of P. talbotii rRNA gene sequence analysis revealed the in Karnataka and Goa have been located

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and their numbers estimated. Similarly Department and other agencies for re- populations of Pseudoglochidion in six sites introduction in the natural habitats. have been estimated. Embryo culture of

Pseudoglochidion is showing positive results CO2 Sequestration for mass propagation. Phyllanthus talbotii has been reintroduced in existing populations In a multicentric project implemented at and new localities. NEERI, BHU, UDSC and RDU, Jabalpur on microbial sequestration of carbon dioxide Species Recovery Programme investigators isolated the enzyme carbonic anhydrase that is responsible for carbon At Shivaji University, Kolhapur in a study sequestration. Bacterial genes were cloned on recovery of RET species of Ceropegia from from some of these microorganisms Western Ghats, micropropagation protocols introduced in to a suitable host. While inside have been standardized for Ceropegia spiralis, bacteria, this enzyme was used for Ceropegia attenuate, Ceropegia evansii and providing bicarbonates in many Ceropegia mohanramii. In another programme carboxylation reactions for bacterial at Shivaji University and ATREE, metabolism. However, when isolated, the microsatellite markers have been developed same enzyme can produce bicarbonates that for Ceropegia fantastica and using these can be precipitated as carbonates of Calcium, markers the genetic variability of the Barium and Strontium when mixed with populations has been assessed. Similarly in solutions of CaCl2, BaCl2 or SrCl2. Under Hubbardia heptaneuron the genetic variability certain conditions, recombinant carbonic across the populations have been assessed anhydrase can also be used for producing using the microsatellites of Oryza sativa. ‘nano-size carbonates’. The carbonic anhydrase produced from bacteria can not

In the species recovery programme at only be used for transforming CO2 into NEHU, Shillong, in vitro mass propagation inorganic mineral carbonates but they can using seeds or suitable explants have been also be used in value addition by producing accomplished for recovery of Nepenthes nano-size carbonates for various biomedical khasiana, Mantisia spathulata and Nymphaea applications. tetragona. Hundred percent of the 1000 plants of N. Khasiana were transferred to the At University of Hyderabad work natural habitat survived. Around 2000-3000 undertaken to study the key responses of plants have been supplied to the Forest photosynthetic enzymes consorted with

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overall plant growth performance in a fast Protein Nano medicine targeted to aberrant growing tree species, Gmelina arborea Roxb cancer kinome was developed at Amrita (Verbenaceae). Gmelina plants were grown Institute of Nanomedicne and Nano science. under ambient and CO2-enriched conditions The invention is related to an endogenous showed positive linear correlation with protein nanomedicine for the treatment of photosynthetic rates and RUBPcase activity drug resistant cancer. Although, molecularly with significant response to CO2 enrichment. targeted small molecule kinase inhibitors Periodic increase in biomass revealed that (SMI) are effective against many types of fast growing tree species like Gmelina cancer, development of point mutations in exhibiting CA - mediated photosynthetic up- the kinase domain leading to molecular drug regulation can be used as potential tree resistance is a major challenge. An species for carbon sequestration under endogenous protein nano medicine was predicted future climate change scenario. developed that can overcome the drug resistance by delivering multiple small At GBPUAT, Pant Nagar, a project on molecule kinase inhibitors targeted to identification of oxalogenic tree and aberrant cancer kinome responsible for the oxalortophic bacteria for long term carbon resistance. In this protein nanomedicine is sequestration was implemented. Number of also conjugated with cell-surface receptors trees have been identified showing the that are over expressed in resistant phenomenon of carbon accumulation in the phenotype. For refractory chronic myeloid form of inorganic carbon (CaCO3). Amongst leukemia, a nano medicine based on human all identified trees, Terminalia alata has shown serum albumin loaded with STATS inhibitor, the real potential in a short time. sorafenib was developed and surface conjugated with transferrin ligands for Nanoscience and Nanotechnology targeted delivery. This receptor plus kinase (dual) targeted’ transferrin conjugated DBT has taken a lead in promoting albumin bound sorafenib’ (Tf- nAlb-Soraf}’ Nanoscience and Nanotechnology programs nanomedicine displayed uniform spherical in the areas including drug delivery morphology and drug encapsulation vehicles, new therapeutics, diagnostics, efficiency of 74%. The enhanced anti- tissue engineering, bio separation, leukemic activity of this formulation was nanotoxicology, agriculture and allied areas. found maximum in the most drug resistant The highlights of the important knowledge patient samples that expressed highest level outcomes are as follows: of TfR and STATS. Thus it was revealed

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that by molecular diagnosis of patients, medical imaging modalities such as novel nanomedicine formulations can be nuclear, magnetic resonance, X-ray-CT and custom designed and developed using this near infrared (NIR) fluorescence, and novel platform of protein nanoparticles. Raman imaging, together with targeted drug or gene delivery properties. A Specifically, the particle is based on nanoparticles of calcium phosphate (nCP) and calcium hydroxyapatite (nHAp), doped and/or conjugated with more than one impurity ion / molecule. The multifunctional nano-composite particle enable combined molecular imaging using single photon emission computed tomography (SPECT), raman imaging, MRI, CT and/or optical near-infrared fluorescent imaging. Another aspect of this invention relates to a method of making B nanomedicine formulations based on the said nCP and nHAp particles, capable of delivering chemodrugs, small molecule inhibitors or nucleic acid drugs such as DNA, RNA, small interfering RNA (siRNA), micro RNA (miRNA) specifically to a targeted disease such as cancer.

Fig. 4.25: A. Design of protein Nano medicine B. Toxicity against drug resistant leukemia An intrinsically fluorescent carbon nanospheres and a Process thereof was In a project undertaken at Amrita Institute developed at Jawaharlal Nehru Center for of Nanomedicne and Nano science, Advanced Scientific Research, Bangalore. multimodal contrast agent based on bio- This invention provides solution of the mineral nanoparticles was developed. A problem involved in delivery of active novel biomineral, hydroxyapatite, based molecules to nucleus, more particularly, nano-contrast agent developed showing intrinsically fluorescent and inherently image enhancement for five different surface functionalized carbon nanospheres

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which are non-toxic. Also, these carbon NPs and PES-DOX-TAR. Lower heart nanospheres (CSP) were absorbed with concentrations with PES-DOX-TAR and PES- CTPB [CSP-CTPB] and the absorbed CSP- DOX NPs suggested the possibility of lower CTPB are permeable to cells with nuclear cardiotoxicity, targeting ability. The present invention also provides a composition, a process to In continuation of the ongoing efforts, various prepare the composition comprising CSP multifunctional nanoparticles were developed with adsorbed active/ therapeutic and different parameters were optimized at molecules and a method for delivering lIT Kharagpur for various medical active molecules in the brain. CSP-CTPB applications. Some of them are (i), (HAT activator), could induce histone Phosphonate-Grafted, Ultra small/ Iron Oxide acetylation in the mice brain, which could Nanoparticles for Combined Targeted Cancer, have a great potential to design (ii) Highly biocompatible and water- therapeutics for neurodegenerative dispersible, amine functionalized magnetite diseases. nanoparticles, prepared by a low temperature, air-assisted polyol process, (iii) A Institute of Chemical Technology, Mumbai, straightforward designed Magnetic Targeted Nano particulate Drug Delivery nanoparticles loaded with doxorubicin for System of Doxorubicin was developed for targeted delivery and MRI contrast agent, Hepatic Cancer Using Asialoglycoprotein (iv) Hydrophobically modified super- Receptor Mediated Approach. paramagnetic nanoparticles for paclitaxel Functionalized Nano particulate drug delivery, (vi) Synthesis, characterization and delivery system (NPDDS) was developed in vitro biological evaluation of highly stable using a novel biodegradable polymer diversely functionalized superparamagnetic synthesized from sebacic acid using a iron oxide nanoparticles: (vii) Folate receptor receptor mediated targeting agent, for targeted, carboxymethyl chitosan function- treatment of hepatic cancer. Accelerated alized iron oxide nanoparticles, (viii) Synthesis stability study of PES-DOX NPs was and characterization of highly stabilized performed according to ICH guideline and manganese ferrite nanoparticles, DOX NPs were found to be stable at the (viii) Magnetite nanoparticles using an end of 3 months at all the test conditions aminophosphonic acid coupling agent, new, indicating shelf life of 1 year. Biodistribution ultradispersed, iron- oxide folate studies (in rats) revealed comparable liver nanoconjugates for cancer-specific targeting, concentrations of DOX solution, PES-DOX (ix) A novel detection of total count of

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Staphylococcus aureus using anti-toxin could clear via intestinal route of antibody labeled gold magnetite elimination. nanocomposite by fluorescence microscopy for Staphylococcus aureus (x) Single step surface At Indian Institute of Chemical Technology, modification of highly stable magnetic Hyderabad, nanomaterials were designed nanoparticles for purification of His-tag and synthesized with fluorophores for proteins, (xi) Design of magnetic Nickel simultaneous use of tracking and delivery. nanoparticles for purification of His- Tagged Thiol was modified as well as guanidine protein (xii) Magnetic nanoparticles as coupled to a single nano-tube. This Supports for Enzyme immobilization and allows the development of cleavable encapsulation functionalization for a wide range of biological cargoes including nucleic acids At Amrita Institute of Nanoscience and (DNA, RNA) and proteins. Many genes that Nano medicine, novel type of stimuli are responsible for the aggressive metastatic responsive graft co-polymeric nanoparticle behavior of the cancerous cells such as Bcl2 based on polymers like chitosan and and cyclin D1 have been efficiently silenced fibrinogen were successfully synthesized as during the nano delivery and cellular a promising smart material for the uptake studies. The serum stability studies controlled cancer drug delivery have proven the novel role of these applications. The preliminary work on nanotubes and their stability for effective radiofrequency was conducted by drug targeting. The binding of the incorporating 5 nm sized Au-NPs in to nanotubes with nucleic acids such as DNA chitosan as well as fibrinogen based thermo was found to be highly efficient at the sensitive polymeric nanomaterial. Due to optimal concentrations. This provides the presence of PNVCL/PNIPAAm, they future hope for the cancer drug delivery showed a temperature-induced phase as it has the advantage of serum stability, transition and tunable LCST at 32-45°C in binding to nucleic acids, thiol bond aqueous solutions. The drug release was cleavage and the organic nature having bio- high at above the LCST of carriers in all degradability. cases compared to that at below LCST, suggesting that these materials could be At Institute of Minerals and Materials useful for the RF based cancer therapy. The Technology, Bhuvneshwar NaoZnO film in vivo Kodak imaging studies on Swiss was used to develop smart packaging albino mice showed that these particles materials. The Nano film could be

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deposited on borosilicate glass and thin are being expended at this center to study Al foil by spray pyrolysis and radio various toxicological aspects of frequency plasma technique. The important nanomaterial. The facilities would cater to feature of the ZnO film deposition in this the needs of the investigators from the investigation includes a novel concept institutions other than this center where zinc acetate was used in the form of a solid pellet which underwent sublimation RNAi Technology Platform at 245°C inside the plasma reactor to produce zinc acetate vapor (precursor) that RNAi approaches are extensively used as was allowed to react in situ with the oxygen tool in understanding various gene silencing plasma (produced by radio frequency in mechanisms. RNAi approach was used in the reactor chamber) resulting in the management of diseases of important crop, formation of ZnO and its film deposition conferring attributes to the plant to combat on glass and Al foil. Such films could be other biotic and abiotic stresses. It has used used for food packaging purpose to as proven excellent tool in the area of increase the shelf life of food items as the therapeutics and new medicine in films coated on the Al foil showed good antimalarial therapeutics, as tool for antibacterial properties toward E. coli and prognosis and diagnosis of for various P.aeruginosa even in dark. It was also cancers using their classic signature. established that ZnO film of more than 500 nm thickness is fit for reuse as food At ICGEB, New Delhi, studies were carried packaging material without compromising out on profiling and mining the sncRNAs the antibacterial activity. Diffusion of Zn2+ from Indian rice varieties tolerant to salinity ions into the bacterial cell is attributed to so as to tap the natural variation existent in be one of the possible mechanisms for the different Indian rice cultivars with reference observed antibacterial activity in the Nano to expression state of the small RNAs and/ ZnO thin film. or their specific targets to generate fundamental knowledge of plant responses Nanotoxicolgy research is being continued to salt/drought stress applications in crop at Amrita Center for Nano Science and improvement. This has resulted in the Molecular Medicine to understand various identification of 210, 169 and 172 known physicochemical parameters associated with miRNAs from three main tissues viz. leaf, toxicity of different nanomaterial. Strong root and flower of local basmati variety; base for nanotoxicology research facilities with 27, 10 and 8 miRNAs being uniquely

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represented in the respective tissues. On characterized for their role in micro RNA comparing the digital data of known rice binding. RNAi based silencing constructs miRNAs obtained from leaves of salt- were developed to silence the viral stressed basmati seedlings and the suppressors and their efficacy of silencing unstressed seedlings of a salt-tolerant was tested under in vivo conditions. Basic variety, Pokkali around 5 salt-specific mechanism by which these viral suppressors miRNAs were identified. Further a tool for are regulating RNAi mechanism was the prediction of mirtrons (a novel class of explored. PRSV-HcPro was found to miRNAs) have been developed and used regulate micro RNAs, directly by binding for predicting mirtrons in rice. Analysis of to them in double stranded form and this 70 introns for minimum number of binding is temperature dependent. CMV- mismatches in the probable miRNA regions 2b, showed differential binding with ds- of the mirtrons and best hairpin structures, miRNAs. ToLCV-AC4 does not bind exhibited 16 most probable intronic directly with the micro RNAs but miRNAs of which 3 hairpin structures constitutive expression of AC4 in tomato showed the lowest free energies. alters host physiology. It was inferred that PRSV-HcPro and CMV-2b are involved Studies carried out at Delhi University on directly in binding with micro RNAs, but Viral Suppressors namely genomic, behaves differently synergism and silencing. These three suppressors viz. PRSV-HcPro, CMV-2b and MYC2 is a very well established ToLCV-AC4 were cloned, expressed and transcription factor in Arabidopsis that

Fig 4.26: The possible mechanisms defense regulation

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receives signals derived from jasmonic inflammation, insulin resistance and poor acid (JA) and activates expression of JA glycemic control in patients with Type 2 inducible genes. Studies were carried out diabetes. to uncover MYC2 homologue from the crop plant rice at JNU, New Delhi. RNAi Role of microRNAs in HIV lines for two putative rice homologues of neuropathogenesis was studied at CCMB, MYC2 were generated through Hyderabad. Expression of functional HIV-1 agrobacterium mediated gene transfer recombinant Tat protein from HIV-1 clade technology in TP309 variety of rice and B and clade C was studied and microRNA functional homologue of Arabidopsis array data were generated through miRNA MYC2 gene from rice (OsMYC2) were array. Expression of selected microRNAs identified. A novel role of MYC2 was was validated through real time PCR and uncovered in activation of salicylic acid targets were predicted of differentially (SA) mediated plant defense against expressed selected miRNAs using bacterial pathogens. bioinformatics prediction tools. The target gene was found, whose regulation is The role of miRNA alterations in the mediated through microRNA expression pathophysiology of Type 2 diabetes was pattern in the human brain microvascular studied at Madras Diabetes Research cells exposed to HIV-1 Tat C protein. Foundation, Chennai. Through this study it was found that miRNAs contribute to the Studies were carried out at NCCS, Pune on disease mechanism(s) underlying insulin silencing osteopontin and its downstream resistance and type 2 diabetes and novel oncogenic molecules as suppressor of the drug targets were identified. Microarray tumor growth and angiogenesis in breast study revealed that muscle-specific miRNAs cancer. It was found that MDA-MB-231 cells (myomiRs); miR-1, miR-133a, miR-133b and transfected with OPN siRNA (SiGENOME miR-206 were down regulated in skeletal SMART Pool) showed significant reduction muscle not only from Type 2 diabetes of Cox-2 and VEGF expression. Moreover, patients but also in prediabetic subjects. MDA-MB-231 cells transfected with OPNi Down regulation of myomiRs was also along with Cox-2i and VEGFi inhibit the demonstrated in high-fat diet-induced cell migration. These results suggested that insulin resistant rats. A sub-study also silencing OPN and/or Cox-2 and VEGF revealed impairment of an immunomiR viz., attenuates the cell migration and tumor miR-146a which links subclinical growth in breast cancer models.

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At Dr. B R Ambedkar Centre for Biomedical complicated network interaction between Research University of Delhi studies were them using Gene Go. The microRNAs undertaken on Deciphering Dendritic cell specifically and significantly expressed in a function during Mycobacterium tuberculosis particular type of leukemia and not in other infection by RNA. Studies resulted in class were further selected for patenting. identification of genes that play a significant role in modulating immune responses to At IIT Madras, work was carried out to M. tb from DCs. Genes such as USP25, Design and Synthesize Peptide Mini-Vectors SNRK and SENP8 displayed broad negative for Receptor Mediated Delivery of siRNAs. regulation with respect to pro-inflammatory Novel peptide sequences were identified responses from DCs as well as regulation which do not exert any negative influence of M. tb survival. Further, many of the genes on the ability of siRNAs in mediating RNAi identified acted in a specific manner that effect and a method was developed to are indicative of fine tuning of immune synthesize enantiomerically pure 2,3- responses during infection and the ability dihydroquinazolinones. A conjugate strategy of M. tb to modulate the activation status of was also established by both C & N-terminus these genes for immune evasion. This of peptides can be kept free of conjugating indicated that these genes played a negative sites to enable the interaction with receptors. role during specific antigenic stimulation as well as whole bacterial infection. Effective siRNAs against HIV-1 Tat and Vif/ Therefore, delineating the mechanisms Vpr were designed at NII, New Delhi. Rz- employed by these genes in regulating some siRNA constructs showed more potent HIV- of these responses could increase 1 activity. Intracellular processing suggested understanding on the roles played by these that siRNAs were processed correctly. It was genes in the pathogenesis of M. tb. also established that bi-specific or multi- specific approach is significantly better than At CCMB, Hyderabad, a microRNA any single antiviral approach. Effective database for leukemia was created which inhibition of HIV-1 gene expression and showed an extensive network between replication could be achieved. Most of the microRNAs and their respective targets. constructs worked against subtype C genes These were further confirmed by creating a which is an important achievements microRNA profile of different leukemia considering >90% infections in India is types, T-ALL and B-ALL. The microRNA considered to be driven by HIV-1 genetic and protein expression profile revealed a subtype C.

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developing a bio-refinery approach for Energy Bioscience Programme selected biomass and other biofuel technologies such as bio-diesel, bio- The Department has been supporting hydrogen and bio-methane. Highlights of programme on Biofuels and Bioenergy with its achievements are: a focus on second generation biofuel using lignocellulosic ethanol and algal biofuel. • Cellulosic Ethanol Efforts were continued for feedstock development, biomass production and The Centre has developed an optimization of production technologies for economically viable and scalable scale-up to make them commercially viable. technology for cellulosic ethanol from The DBT–ICT (Institute of Chemical all types of agricultural residues and Technology) Centre for Energy Biosciences energy crops. These features include (CEB) has been established at Mumbai with biomass fractionation and enzymatic the primary focus on developing saccharification to fermentable mono- biotechnologies for deriving energy from sugars and lignin followed by renewable resources. The DBT-IOCL Centre conversion of both C6 and C5 sugars to for Advanced Bioenergy has been ethanol. The ICT Technology for established at R&D IOCL Faridabad. Cellulosic Ethanol, used to design a 10 ton biomass/day processing plant to Salient achievements of the New Initiatives convert rice/wheat straw ; bagasse, and taken and ongoing programs during the many other varieties of biomass into year are briefed below. sugars and lignin, and onto ethanol for use as fuel or chemical intermediate. The Energy Bioscience Centres designed pilot plant has been erected at the India Glycols Ltd. site at Kashipur, DBT-ICT Centre for Energy Biosciences Uttarakhand with suport from BIPP, BIRAP, scheme of the department of The DBT–ICT (Institute of Chemical biotechnology. Technology) Centre for Energy Biosciences (CEB) is developing technologies for • Algal Biotechnology deriving energy from renewable resources. An emphasis was given on improved bio- A state-of-the-art laboratory for algal ethanol production from any given biomass, biotechnology has been set up with basic

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infrastructure coupled with 1000L and model describing the underlying 5000L raceway ponds with novel designs phenomena and affording design of the as well as set of 10L controlled enzyme reactor system has been photobioreactors, all equipped with developed and implemented on microprocessor based SCADA controlled industrial scale with provision for re- systems. R&D capability in the areas of use of the cellulolytic enzymes over Agrobacterium mediated nuclear many cycles. transformation has been developed with selected algal strains. • Synthetic, Molecular Biology and Protein Engineering • Fermentation Technology Notable successes of the programme are Under fermentation technology, high thermostable β-xylosidase from cell density and immobilized cultures Geobacillus thermodenitrificans, over- were implemented for tenfold higher expressed in Escherichia coli; endo- rates of fermentation of sugars to cellulase and â-glucosidase with lower alcohols and acids, without impairing substrate inhibition and fusion proteins product yields. Metabolic flux analysis designed and expressed in E. coli in coupled with metabolic engineering has collaboration with ICGEB, New Delhi; been applied to several fermentation and design and expression of a non- systems aimed at production of primary specific lipase expressed in Y. lypolytica. as well as secondary metabolites systems exhibiting multiple steady DBT-IOCL Centre states and hysteresis have been modeled in collaboration with School DBT is setting up the DBT-IOC Advanced of Chemical Engineering, Purdue Bioenergy Research Centre. This centre is University, USA. coming up at Indian Oil’s R&D complex at Faridabad as a partnership centre of DBT • Enzyme Technology and IOC. An MoA was signed on 11th August 2011 with Indian Oil Corporation, Novel two step rapid process has been the largest Public Sector enterprise in the developed and patented worldwide for country with MD of Indian Oil Corporation. enzymatic saccharification of cellulose The centre aims at the following major and hemicellulose. Mathematical objectives:

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• To conduct a multi-disciplinary evaluation and accessioning to identify bioenergy research involving biology, superior material from existing natural chemical and material sciences etc. variations. This germplasm improvement programme was launched to enhance the • To provide a platform for integrating productivity and yield. dis-jointed research activities pursued in several areas related to biofuels by A total of 13 institutions are working on various institutes. various aspects from survey of superior material to experimental plantation and 500 • Development of “institutional accessions were found promising on the capability” to address the bioenergy basis of percentage oil and tolerance to local need of nation based on “science - conditions which were used for raising enterprise model”. plants.

• Provide National capability of pilot level Operational guidelines have been framed scale-up of developed technologies. for the Micromission on production and demonstration of quality planting material Bioenergy Center for Research in Synthetic of Jatropha, in consultation with scientists Biology is being set up at ICGEB New Delhi and experts in the field defining criteria for considering ICGEB’s strength in Synthetic selection of quality material. Multilocation Biology Research. trials of 20 promising accessions was initiated in 2007 to study the effect of set Biodiesel agronomy practices, soil and agro-climatic conditions on performance of accessions at Feedstock improvement and Multilocational with 9 partner institutes. Trials In addition to agronomy trials, 100 The thrust of the programme was on accessions are also being tested for Biodiesel-feedstock development and silvicultural trial along with agro climatic improvement of Jatropha under the micro performances. mission on production and demonstration of quality planting material. The department These accessions have been further bulked of biotechnology has initiated systematic up under controlled nursery conditions. programs on germplasm collection, DBT Network has resource of 500 selected

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accessions for future improvement, biosynthesis and oil content in Jatropha multiplication and bulking. This resource seeds through generation of ESTs, full length base is being conserved at five centres cloning of fatty acid biosynthesis genes and (Tamil Nadu, Odissa, Haryana, Assam and development of molecular markers (SSRs/ Gujarat) in the country. SNPs) either through ESTs or comparative genomics with caster bean. The following Conservation and resource maintenance of leads were obtained in the past 4 years: selected Jatropha germplasm • Total of 16,000 ESTS and 70,000 short Jatropha germplasm resource centres have been transcripts have been generated from established at 5 different states and institutions different developmental stages of for Conservation of 500 accessions of Jatropha Jatropha seeds. curcas and as clonal and seedling material for multiplication and bulking. • All genes involved in fatty acids biosynthesis, including seed oil Germplasm banks of J. curcas were accumulation have been cloned to full established at Kudankulam and Jeypore length. during the year. The project aims at standardization of the cultural practices and • Gene constructs for Jatropha seed oil systematic documentation of the agronomic increase have been developed for major characters of the accessions. genes. These genes have been functionally validated in Arabidopsis or R&D in Jatropha Tobacco for increase in oil content.

A Network Project on Gene Prospecting in • Increase in Arabidopsis seed oil content Jatropha for High Seed Oil Content (~20%) has been observed through a Jatropha gene, JcDGAT under a seed Within the Jatropha R&D Network six specific promoter. centers i.e. Jayee University Solan, IIAR Gandhinagar, VMSRF Bangalore, SRM • Transformants of Jatropha have been Unjversity Chennai, NBRI Lucknow, MSSRF developed with a multigene construct Chennai were involved. The overall goal of (LPAAT from coconut and FAT A from different R&D projects has been to Jatropha) and their seed oil content understand molecular biology of fatty acids analysis is being done.

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• Large numbers of molecular markers of cellulosic biomass (rice straw, cotton (SSRs/SNPs) have been developed either stalk, sweet sorghum, switchgrass, Prosopis from ESTs (EST-SSRs) or comparative juliflora and Lantana camara) were carried out genomics with caster bean (SSRs/SNPS). at CIPHET Ludhiana where two stage pretreatments involving an alkali and an • Whole genome sequence of Jatropha has acid was tried for cotton stalks, Lantana been computationally analyzed for all camara and Prosopis juliflora which resulted SSRs. in 85% or higher delignification for all the three residues. Enzymatic hydrolysis of the Transesterification above treated substrates resulted in overall hydrolysis efficiency of 82% and 84% for The crude Jatropha oil has FFA about 5% cotton stalk and Lantana camara, respectively which should be below 0.5% for further at 15% substrate loading. transesterification. Hence 50 kg batch experiments on esterification were Enzymatic hydrolysis and fermentation of successfully carried out at IICT Hyderabad lignocellulose to reduce the FFA to below 0.5%. Almost complete conversion of oil to esters could ICGEB is developing a technology for cost be achieved. effective production of biolacohol from lignocellulosic biomass and has discovered Lignocellulosic based Bio-ethanol novel a-endoglucanase (Endo5A), a- glucosidase (Gluc1C) and xylanase (Xyl11D) Department has been supporting various from a Paenibacillus sp (deposited at MTCC projects on cellulose Bioethanol which with accession no. 5639) isolated from the includes developing technology for gut of an insect living on the cotton plant pretreatment of substrates, enzyme and cloned and expressed them in E. coli. development for breakdown of different substrates, ligocellulosic conversion from Efforts are continued for optimization of lab to pilot scale, process development and high-level extracellular expression of these downstream process technology. enzymes in E. coli for effective hydrolysis of plant biomass condition. Higher Pretreatment and Pelletization expression level of pyruvate dehydrogenase operon (PDH) resulted in higher ethanol Studies on pelletization and delignification yield. Further deletion in the competing

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pathways resulted in reduced production 86% carbohydrate recovery and 84-86% of lactate, succinate and acetate and higher ethanol fermentation efficiency. The process ethanol yield. The strains SSY07 produced has been valildated at DBT-ICT Centre for ethanol as major product and acetate and Energy Biosciences, ICT Mumbai. format as minor products from glucose and xylose whereas strain SSY10 produced Bioethanol from Cassava Starch Flour ethanol as only product with higher yields Residue from both the sugars. A significant achievement of the work A new yeast surface displaying vector was carried out at CTCRI Thiruvanthpuram is developed at Osmania University having standardization and development of process TEF, a constitute promoter, genticin (anti- technology for production of ethanol from biotic) cassette for selection and ARS CSFR, a solid waste discharged from cassava sequence for maintaining high copy number starch industries. Very high ethanol yield in yeast. Pretreated rice straw was used for (390 l/tone of dry CSFR) was obtained in simultaneous saccharification and the new technology, making CSFR an fermentation using this construct and in alternative substrate for ethanol production. initial studies 80% hydrolysis and 95 % fermentation efficiency was obtained in 36 Biobutanol hours. Butanol is being looked upon as a Process validation of Lignoceullulosic sustainable and next generation biofuel. ethanol production Studies are in progress for production, process optimization, scale up at UDSC New At UDSC New Delhi a pretreatment Delhi and ARI Pune. Process optimization method, which fractionate ~100% for higher butanol production was carried hemicellulosic sugars and remove ~ 90% out using one variable at a time and lignin from Prosopis juliflora and Lantana statistical approach (Plackett-Burman and camara has been optimized. The ethanol Response Surface Methodology). An production from both the lignocellulosic increased yield of 17.50 g/L of butanol substrate i.e., P. juliflora and L. camara has (ABE-23.0 g/L) was achieved after fed batch been scaled up successfully to 20L and the studies. The production of butanol was mass balance studies of ethanol production successfully scaled up to 30 L fermenter from both the substrates have revealed 83- under the optimized conditions (16.40 g/L)

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(Photo 2).To purify butanol from the demonstrated that C. butyricum TM 9A strain fermentation broth gas stripping was could produce 14 liter of pure hydrogen adopted with recovery of 50% followed by from 10 liter of basal nutrient solution. further purification by pervaporation with 40% recovery and 100% purity as confirmed Algal Biofuel by NMR analysis. Algae, as a research material for biodiesel has been identified as a priority area of research. Studies have been initiated to collect, identify and characterize algal strains which will have more oil/lipid content. To have large amount of biomass, mass cultivation has been started using open pond system, (Raceway ponds), photo- bioreactor etc. Besides, growth conditions of selected species are being optimised for high oil yield. Under this algal network Fig. 4.27: Butanol production at 30 L Scale programme 12 national laboratories/ institutions/universities are involved from Bio Hydrogen across the country.

Department has recently initiated supporting Algae Collection and Repository research projects on production of biohydrogen realizing the potential of Conservation and characterization of Fresh biohydrogen as a fuel for future. TERI , water Cyanobacteria / microalgae at IBSD, New Delhi has taken a lead in this regard Imphal, Manipur with support from DBT. New Clostridium butyricum strain TM 9A has been isolated, Nine hundred thirteen (913) cyanobacterial optimized and studied for biohydrogen isolates have been purified, morphologically production using different cost effective characterized and preserved at Fresh water substrates and maximum hydrogen Repository set up at IBSD Imphal. These production was obtained at 2.5% molasses isolates belong to 32 genera collected from concentration. The process was also been different ecological habitats of North East scaled up at lab scale and results Region of India. Besides the cyanobacteria

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a total 315 micro-algae also been collected Almost 126 marine cyanobacterial strains from North East and Western Maharashtra. have been supplied to 30 research institutions with in India for research Algae Collection and maintenance- purposes. In order to enrich the microalgal Marine water (NFMC) repository, coastal stretch from Thengapattinam to Ervadi was also covered National Facility for Marine Cyanobacterial under survey. repository at Bharathidasan University has been upgraded to 527 marine All the strains in the repository have been cyanobacterial strains collected from the identified based on morphological means. coastal areas of Tamil Nadu, Puducherry, Molecular confirmation with selected 3 Gujarat and Andaman island. The facility molecular markers viz. 16SRNA, ITS and has been selected for the Arctic summer cpc regions is in progress. So far, 60 isolates expedition for the microalgal survey. So of the collected samples have been screened far, 19 cryophilic cyanobacteria and 11 for different parameters like oil content, fatty microalgae has been isolated from Arctic acid profiling, colour, odour, pH, specific survey and maintained in the repository. gravity, refractive index, and density.

Fig. 4.28: NFMC Repository

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Cultivation / Biomass Production aggregating the algal cells together enabling Technology / Biomass Harvesting and easy harvesting. Harvested biomass was Processing dried and lipid extraction was carried out with benzyl alcohol. Methods are being optimised to develop efficient oil extraction process from algal Algae Production using industrial effluents oil at pilot scale at Bharathidasan University. Selected strains have been optimized for Different industrial effluents like mass cultivation (25 – 75 litres) under semi pharmaceutical wastewater, dairy continuous mode. At present detail wastewater, winery wastewater and sewage investigation on scaling up of cultivation of have been studied for lipid productivity by alga in continuous system at 250 liters is in Green Micro Algae at TERI. Green progress optimization of downstream microalgae were found to be efficient in processing methodologies is being carried removing nutrients and pollutants from out. industrial wastewaters and produce biomass and lipids for biodiesel preparation. At IIMT Bhuvaneshwar eight numbers of Raceway ponds, each having 100 sq mt Biogas (Biomethanation) surface area and 0.5 m depth with capacity of 40,000 liters each have been designed, Validation of exogenous enzyme constructed and put into operation. Raceway application for enhancement of ponds have the provision for necessary biomethanation process was studied at carbon dioxide fluxing, control and ARI Pune. The studies carried out to instrumentation stations, paddle wheel for validate the effect of enzyme addition on proper mixing, harvesting system using anaerobic digestion of vegetable waste in vibrating membrane filter, etc, motors and batch experiments have shown that

CO2 sparging facility etc. enzyme addition increased the methane yield in batch mode. It was observed that Biomass harvesting was a challenging issue single cellullase, alone can be sufficient due to very small cell size and their slow to show good increase (ca. 1.5 fold) in the rate of colony formation. Hence poly- methane yield as compared to dual electrolytes like sodium alginate and enzyme addition. Enzyme can be added chitosan were used out of which sodium directly into the digester instead of any alginate was found to be effective in pretreatment.

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Capacity Building is for 5 years, which in exceptional cases, may be extended by another 5 years. Four The Department has also instituted-Energy candidates have been selected for this Bioscience Overseas Fellowships for fellowship joined host institutes ICT scientists of Indian origin who are working Mumbai, and IISER Calcutta. outside the country in the field of Energy Biosciences (including Biofuels, Bioenergy The Department has also initiated a scheme etc.). The main objective of the scheme is to -National Energy Bioscience Chair” to have support scientists of Indian origin who wish excellent team leaders in the Bioenergy area to return to the home country and pursue who can help in building innovative teams research of high calibre in the area of Energy to address the major challenges in this Biosciences. The duration of the Fellowship sector.

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168 Chapter 5

BIOTECHNOLOGY PROGRAMMES FOR SOCIETAL DEVELOPMENT

The programme was continued for the socio- production. Vaccination and treatment economic upliftment of SC/ST population. camps were organized with the help of State Training and demonstration programmes in Govt. Livestock development officer and various biotechnology based activities were more than 3500 animals were treated for undertaken on proven and field tested various diseases. Animal owners were technologies related to animal husbandry, provided medicine for deworming and fish seed production and catfish culture, mineral mixture during the animal health seed production, agro technology, camps. Beneficiaries earned around Rs. vermicomposting, integrated farming 20,000/- annually through adoption of interventions and organic cultivation of different animal husbandry practices. spices, medicinal and aromatic plants and mushroom cultivation etc. Various In an another project on enhancement of biotechnological activities undertaken could income generation of SC/ST farmers was benefit SC/ST target population under the implemented in Kota district of Rajasthan. programme. Some highlights of the Improvement of animal health & their programme area are as follows: productivity through nutrient rich animal feed blocks were undertaken by Gramin Programme for SC/ST Population Vigyan Kendra, Society for Environment & Development. Awareness programmes Animal Husbandry were organized 120 beneficiaries were provided intensive training on various A Project was undertaken for the socio aspects of animal health and productivity. economic upliftment of SC/ST farmers SHG groups were formed and engaged in through animal husbandry. Beneficiaries making the animal feed block under the trained on goat rearing, dairy farms, poultry brand name ‘Pashu Amrit Battika’ and farms, improved health care, clean milk marketing. Farmers feeding their animals production, value addition in milk & milk realize increase in the milk production and products. Training for adoption of scientific increase in rate of survival among adult & animal husbandry practices to improve the kids.

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Training & demonstration on Emu and Senapati district, Manipur. One hundred Turkey rearing was implemented by Krishi poor tribal beneficiaries from Kangpokpi Vigyan Kendra-Sylvan, for the economic T.D. Blocks including women, landless upliftment of scheduled tribe families in persons, and educated unemployed youths Senapati district, Manipur. Twenty SHGs were selected and trained through SHG formed by identifying 200 tribal farmers groups on advance management of crossed including women beneficiaries belonging to bred piglets. Beneficiaries were provided BPL from two T.D. Blocks namely Saitu- piglets (one male and one female), shade Gamphazol and Kangpokpi. Eight training feed materials and medicines. Trained programmes conducted on Emu and Turkey beneficiaries earned an average annual rearing and provided knowledge on various income of Rs. 28800.00 per year through technical and financial aspects and helped piggery. the beneficiaries in the establishment of infrastructure for setting up Emu and Turkey Fish Seed Production enterprises. A nucleus centre of Emu and Turkey were established to popularize, Carp seed production for the livelihood of replication and supply of chicks to the SC/ST communities in Nayagarh and interested farmers. Mayurbhanj districts of Odisha were operated by CIFA, Bhubaneswar. FRP carp Another project on Socio-economic hatchery units installed in various villages development of resource poor tribal in these two districts for training on carp families was implemented on piggery in seed production, and also on establishment of mobile hatchery for fish seed rearing. Around 200 persons trained on different aspects of the freshwater aquaculture, carp hatchery operation, induced breeding, seed rearing and their management. The spawn produced from the hatcheries were stocked in nursery ponds for fry and fingerling production with higher survival rates in advanced fingerlings. Awareness programme undertaken by involving various stakeholders including hatchery operators.

Fig. 5.1: Osmanabadi Buck in the Nondescript Goat Flock One of the beneficiaries from Nayagarh

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District, Odisha, awarded with a scroll of of Moina, Daphnia and Rotifers. Adoption honour on National Fish Farmer’s Day of catfish culture technology by unemployed observed at CIFA, Bhubaneswar. youths earned about Rs. 60,000/year.

Catfish Culture Seed Production

Propagation and demonstration of native Training programme was conducted on catfish culture for self employment of SC/ production of quality seeds of groundnut ST farmers were taken up at St. Xavier,s to meet the seed demand locally and also College, Tamilnadu. Commercially to increase the livelihood of the famers important catfishes viz; Heteropneustes fossilis from Bijapur district of Karnataka. A series (singhi), Mystus gulioMystus montanus and of lecture and interaction sessions were Ompok bimaculatus maintained at Aqua-farm organized for 150 farmers of Kumathe and brooders of H. fossilis, M.gulio, village on various aspects of quality seed M.montanus, O. bimaculatus were injected production of groundnut harvesting, with hormones for spawning and processing, storage and maintenance of larviculture. Training programmes were seed quality. Ten adopted beneficiaries conducted at Palayamkottai, Pettai and were provided breeder seed of high Srivaikundam through which 200 SC/ST yielding variety having resistance to late farmers trained on seed production, larval leaf spot and rust. Farmers were rearing and culture of native catfishes. encouraged to take up commercial seed Beneficiaries have undertaken plankton production programme under integrated culture and succeeded in mass production crop management.

Agro technology

A programme was undertaken for dissemination of need based technology for economically productive agricultural practices. Awareness and training programs was conducted on various aspects of soil and water testing, fertilizer application, green manuring, INM and IPM technologies.

Fig. 5.2: Fish catch haul Commercial crops on cultivation of paddy,

171 Biotechnology Programmes for Annual Report : 2011-12 Societal Development blackgram, cashew, vegetables, Jowar; economic and self-sustaining their backyard kitchen gardening were introduced livelihood. One hundred beneficiaries to the farmers with the integrations of adopted vermicomposting for income animal husbandry practices. Upgraded generation. breeds of cattle and poultry were introduced to the farmers and they were trained on In another project at Gulbarga University, advanced management practices which vermicomposting was promoted for the resulted an additional family income of benefits of the target populations in different Rs.10,000/-. Through adoption of integrated villages in and around the university. farming system drudgery in women were Beneficiaries were provided the literature reduced to an extent of 50% with increased published in local language. farm efficiency. Integrated Farming Vermicomposting Biotechnological interventions through Training and demonstration activities integrated farming were implemented by vermicomposting and use of vermicompost Shri AMM Murugappa Chettiar Research on vegetable cultivation were undertaken Centre (MCRC), Taramani, Chennai to for income generation of SC beneficiaries provide alternative income to SC/ST selected in consultation of local SHGs, Gram targeted population. Various interventions Panchayats. Vegetable seed for kharif and viz. vermicomposting, mushroom Rabi season distributed to 50 beneficiaries cultivation, charcoal briquetting and clonal and supervised their demonstrations at field propagation were introduced and level. By adopting this simple and beneficial established vermicompost pits, mushroom technique, beneficiaries realized increased cultivation sheds, charcoal briquetting production. units, net houses. About 664 beneficiaries covering 160 villages through networking Dissemination of vermicompost production partner NGOs were trained on income technology was taken up for farmers in generation activities in addition to their Mysore district of Karnataka. The wastes present occupation. Adaptation of generated from agriculture were used for biotechnological interventions by the vermicomposting. Beneficiaries from 15 beneficiaries gained alternative livelihood villages were trained on various aspects of interventions through utilization of the vermicomposting technology for the locally available resources.

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Organic Cultivation of Spices unit were centrally set up. Kisan awareness programmes were organized for the farmers Peermade Development Society, Kottayam of adjoining villages also for wider adoption has implemented a project on cultivation of of these crops and also trained to adopt pepper for the tribal farmers of Idukki rainfed cultivation of medicinal plant. SHG district of Kerala. Fifty tribal farmers from groups were formed to sensitize the farmers different Self Help Groups were provided to take up commercial cultivation. training on the scientific organic management of pepper with combined use of different biological control agents, biopesticides, botanicals and trap crops. Trichoderma and Pseudomonas formulations were supplied to the farmers for application in their crops. Farmers trained on vermicomposting, multiplication of VAM and production of neem seed kernel extract and also provided small vermicompost facilities for production and Fig. 5.3: Interaction with the farmers on cultivation of MAP use in their fields and regular monitoring of their field crops. Demonstration plot was Mushroom Cultivation established under the project to carry out the farm trials for the efficient organic control Entrepreneurship development of pests and diseases. programme on Oyster Mushroom Cultivation was introduced for SC/ST Medicinal and Aromatic Plants target population in Tiruchirappalli District by Bharathidasan University, TN. Programme was undertaken on Spawn production laboratory was set up Empowerment of SC/ST community of and 50 selected trainees were provided Bundelkhand region by introducing the hands on training on mushroom cultivation of medicinal and aromatic plant cultivation, spawn preparation, bed and processing through CIMAP. Ten farmers preparation, diseases prevention and each from two bio-villages of Jhansi were marketing. A training manual prepared in trained on raising the nursery of Palmarosa local language distributed to the and Lemongrass. Distillation/processing participants. Some of the entrepreneurs

173 Biotechnology Programmes for Annual Report : 2011-12 Societal Development trained have already initiated commercial so that authentic planting material could be mushroom cultivation. supllied to the interested growers and set up centrally located distillation unit. Hands- Programme for Rural on training was imparted to around 130 Development interested growers on the agro and nursery technologies of selected MAPs and vermi- The programme was continued for the socio- technology. Demonstrations conducted in 34 economic upliftment of rural population. villages, and farmers earned a substantial Various training and demonstration profit both from sale of planting materials programmes in biotechnology based and production of oil/herbs from various activities were undertaken on proven and medicinal and aromatic plants. field tested technologies relating to quality planting material, bio-control agents, Bio-control agents vermicomposting, organic pepper cultivation, lac cultivation, sericulture, A project on popularization of bio control animal husbandry, goat rearing, quail agent was undertaken by Indian Institute of production, rabbitry and health care etc. Pulses Research (IIPR), Kanpur to provide Demonstrations and trainings activities benefits to the farmers of Bundelkhand undertaken could benefit the rural people region of UP. Awareness campaigns were through various biotechnological organized on pod borer (Helicoverpa armigera) interventions. The department supported management. Farmers were given hands on eight bio-events to exhibit various rural experience on application of HaNPV and products & processes for their promotion & NSKE in the chickpea crop and monitoring adoption at the rural level. Some highlights of pod borer population. Demonstrations of the programme area are as follows: were organized for pheromone traps, spray of neem based product, spray of HaNPV, Quality Planting Material spinosad for monitoring of pod borer, for repelling egg laying, management of early A project on Developing Quality Planting and late instars in 20 ha benefitting about Material Resource Nodes for Medicinal and 90 farmers. Aromatic Plants (MAPs) was implemented in villages of Sitapur, Barabanki and Amity University has undertaken a training Lucknow districts in U.P. through Agro and programme on eco-friendly integrated Nursery Technology by CIMAP, Lucknow management of major soil born fungal and

174 Annual Report : 2011-12 Biotechnology Programmes for Societal Development root knot nematode diseases infecting throughout the project implementation. The vegetables. About 264 selected farmers were efficacy of vermicompost was assessed on trained from western U.P. through brinjal, chilli and ragi crops. The awareness programmes on management of demonstrations benefitted more than 1000 root-knot nematode infecting vegetables. farmers. A pilot training Centre was Eco-friendly, cost effective disease established at the campus to provide inputs management using sustainable components and training. More than 200 PG students like antagonistic fungal bio-agents have also trained on vermicomposting and (Trichoderma spp. and paecilomyces lilacinus as also use this unit for converting waste into core component), oil seed cake and botanical vermicompost in nursery. antagonist were demonstrated at hot spots with indigenous technology. The IPM Organic Pepper Cultivation package significantly helped in improving seed germination and yield increase from A project on scientific cultivation and value the crops. Farmers made the fungal bio- addition of pepper to increase agricultural agents themselves, applied in their own income of the marginalized farmers in fields and got good result. Udumbanchola Taluk of Idukki district was undertaken by Kottayam Social Service Vermicomposting Society, Kottayam. A laboratory was established at Thadiyampadu, Idukki A project on vermicomposting was District for multiplying the Trichoderma and implemented for the Socio-economic VAM fungi to control the Quick-Wilt disease Development of Rural people from in Pepper. About 227 farmers were trained Bangalore District, Karnataka. A total of 146 on rapid multiplication technology of demonstrations on vermicompost pepper, biological control agents production production were conducted for the and value addition. Trained farmers realized beneficiaries. Beneficiaries were trained on good income through adoption of micro- preparation of vermicompost units, propagation technology and organic introduction of earthworms, watering and cultivation of pepper. A central nursery was maintenance, protection against ants and set up at its regional in Idukki district to rodents, collection of vermicompost, produce disease free pepper. Rapid processing and preservation and preparation multiplication technology was used and of vermi-wash. Continuous monitoring dieses free plants were distributed among support was extended to the beneficiaries the marginal farmers to set up their own

175 Biotechnology Programmes for Annual Report : 2011-12 Societal Development nursery. Farmers were trained on processing popularization of Chawki Rearing Center of white pepper production and they are (CRC) model developed by CSRTI, Mysore earning a better price of Rs. 160/- per kg in identified clusters of Karnataka, Andhra for white pepper while green pepper fetches Pradesh and Tamilnadu. CRCs were only Rs. 80/- per kg. established in identified cluster areas and training programme were conducted for the Lac Cultivation selected entrepreneurs and their workers on Chawki garden and Chawki rearing Lac cultivation was popularized for management. Progressive sericulture farmers economic upliftment of marginal farmers in were supplied chawki reared worms in co- Kandi belt of Jammu, J&K. Awareness and ordination with the State Departments of motivation programme was organized and Sericulture Karnataka, Andhra Pradesh and on-farm trainings conducted at zonal or Tamilnadu. Ten days certificate training district levels in Jammu, Kathua and Samba programme on commercial CRC districts for the potential growers to take maintenance and management for CRC up lac cultivation on regular basis. About owners were organized at CSRTI, Mysore. 234 potential growers were identified where CRC owners started earning regular income adequate potential for lac cultivation exists, and are repaying their loans through i.e. vicinity of forest and availability of sericulture activities. useful trees. Five field demonstrations were conducted and 43 farmers were trained on Artificial insemination state of art technology on lac production including pruning, inoculation, crop Tharparkar breed of cows one of the high protection and lac processing and brood milk yielder in India is mainly reared in production on Palas and Ber. Two hundred desert area of Rajasthan. This cow is on an trees of Palas and Ber were inoculated, which average producing 2179.43±16.76 kg milk yielded about 334 kg of brood for during full lactation period of average inoculation. Seven farmers adopted the length as 314.78±5.23 days. Five bull calves technology and started earning with more of Tharparkar breed were selected from than 100 days employment per annum. Central Cattle Breeding Farm (CCBF), Suratgarh and monitored for their growth Sericulture till the semen collection age by BAIF foundation for desert areas of Rajasthan. CSRTI, Mysore is pursuing a project on Door step breeding services were provided

176 Annual Report : 2011-12 Biotechnology Programmes for Societal Development to the livestock owners extending artificial for enhancing the income of the small and inseminations service to 2508 cows and marginal farmers. About 1154 beneficiaries confirmed 1,013 pregnancies. Around 700 were trained on the various aspects of goat farmers’ were trained on new technologies farming and need based animal health care. of general cattle management practices. The Video show on field day was organized for popularization of the A.I. among the farmers motivating the farmers to take up the goat especially those who are keeping farming as an income generation activity. Tharparkar animals raised the confidence Three hundred bucks of Osmanabadi breed level in dairy business. were supplied to the beneficiaries by KVK Durgapur, Amravati which gave them Goat rearing confidence and encouragement. Improved management practices adopted by Project on dissemination of technology on beneficiaries resulted multiple birth, Berari goat rearing was successfully reduced inter kidding period and body implemented for Socio-economic upliftment weight gain at an early age. of farmers and youth of ten villages of suicide prone Akola district of Maharashtra. Quail Production 59 hands on training and demonstrations were conducted benefitting 680 farmers. For Demonstration and training programme on reducing mortality and morbidity rate in commercial quail production was goat due to diseases, 51 goat health camps undertaken in rural areas of Parbhani district were organized in villages in which of Maharashtra by College of Veterinary and vaccination and deworming of goats were Animal Sciences, Parbhani. Mass awareness undertaken. Berari goat unit of two female camp on quail farming was organized and and one male were distributed to 50 demonstration of quail, egg and meat beneficiaries on 75% subsidy basis. The production was conducted benefitting beneficiaries have started earning around around 100 women farmers. Scientific Rs. 800 /month through sale of goat, milk knowledge on Japanese quails farming and manure. Training manual of book and disseminated to the women beneficiaries leaflets prepared in simple local language covering preparation of cages, feed, distributed to the beneficiaries. vaccination, incubation, marketing etc. Cost economics per unit of quail for meat and Local non-descript breed upgraded with egg production worked out which indicated improved Osmanabadi proven to be useful economic viability of quail production to

177 Biotechnology Programmes for Annual Report : 2011-12 Societal Development gain an income about Rs. 3000 to 4500 per respiratory diseases. It also covered months. The intensive training was imparted assessment of sanitation and hygiene on commercial quail farming in Parbhani conditions of the schools and drinking water. district. A booklet was brought out on quail Early detection of health related problems farming for distribution among the in children and their proper treatment beneficiaries. through referral services were undertaken. Assessment made on quality of the mid Rabbitry day meal distributed in the school and provided special aids as medicines, Amity Institute of Phytochemistry and spectacles, hearing aids etc. to the needy. Phytomedicine Trivandrum conducted Health Cards prepared and updated of child training programme on Rabbitry and Fur health profiles to be maintained in school. Processing for the benefit of SC/ST youths Distribution of posters and campaign of Trivandrum District, Kerala. A model leaflets to disseminate information on Rabbit Farm and Training Centre was set health/hygiene etc. Students and parents up in Kodunganoor Village and three units were given counselling on health care of breeding stock of rabbits consisting of 10 aspects. The project has benefitted more than females and 2 males to each beneficiary 1,50,000 children studying in MCD schools provided which facilitated breeding rabbit of Delhi along with slum kids. strains of New Zealand White, Soviet Chinchella and Grey Giant. A project on awareness creation among the doctors and women of rural people was Health & Awareness undertaken for preventable causes of mental retardation in new born babies through A school programme named Health Safari collaborative efforts of Sanjay Gandhi was successfully implemented by Postgraduate Institute of Medical Sciences, GAMANA, Hyderabad- Andhra Pradesh in Lucknow and Chatrapati Shahuji Maharaj collaboration with Mass Awareness Society. Medical University, Lucknow. An awareness The project involved health check-ups of creation programme for preventable causes school children with the help of health of mental retardation, namely; congenital department. The health check-up hypothyroidism, biotinidase deficiency and programme collected data on growth galactosemia was undertaken and the monitoring (BMI), dental hygiene, population from rural and lower / lower occurrence of diarrhoea and acute middle socioeconomic class were screened

178 Annual Report : 2011-12 Biotechnology Programmes for Societal Development by organizing camps in collaboration with Information brochure and papmhlets were district Hospitals and NGOs working in the prepared in local language for destribution health sector. About 4000 neonates have among the parents. A feedback received been tested for these three disorders. about the usefulness of new born screening programme undertaken. Most of the families coming for retesting their babies indicating their commitment. The project is now operating in a full swing and likely to test more than 15,000 babies.

Soya Milk Processing:

Training on soybean processing and its utilization for employment generation among weaker section was undertaken in Fig. 5.4 : Health safari project implemented Amravati District by KVK, Durgapur at NDMC Schools

Fig. 5.5 : Screening of new born babies for mental retardation

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Amravati, talukas namely Nandgaon (Kh) and Bhatkuli. A society called Soybean Programmes for Women Processors Society consisting 152 members was formed. All together 58 beneficiaries Around 10,000 women have been benefited from these two talukas were trained for through various ongoing and new projects soybean processing. The trainee from said supported under the Programme. The villages started producing the noodle and programme is basically women-centric and papad from soy flour and also soy milk, covers training, field demonstrations, soy paneer successively which are being extension activities, enterprise development sold in the local market. etc. in the subject areas such as horticulture, mushroom cultivation, biofertilisers, Bio-events biopesticides, aquaculture, animal husbandry, poultry farming, production of Eight bio-events were organized by various diverse value added marketable products agencies namely D. S. College Aligarh, JSS, which may facilitate women to improve their Mahavidyapeetha, Mysore; VKS, Krishi income and socio-economic status. The Vigyan, Unnao; Centre of Technology & programme also supports research projects Entrepreneurship Development, Sultanpur; focused on women health care, nutrition and Kottayam Social Service Society; Suvide hygiene related aspects. During the year, Foundation, Washim; Dhanalakshmi nearly 30 ongoing projects have been already Srinivasan, College of Arts and Science for supported. In addition, 7 new projects have Women, Perambalur, TN and Deendayal already been sanctioned and 5-6 more are Krishi Vikas Avam Anusandhan Samiti, likely to be supported during the year. Bhopal (MP) for Awareness Creation and Highlights of the programme are as follows: Promotion of Biological cum agricultural inputs and value added products among Vermicomposting and Organic farming Self Help Groups. Through this programme awareness was brought among farmers on Nearly 2000 women farmers of Tiruvallur new agricultural practices, tools etc. to district in Tamil Nadu were imparted enhance their agriculture produce and training on preparation of vermicompost and cottage industry. About 5,00,000 people botanical pesticides. Each women participated in the Bio-events with the beneficiary is reported to earn around Rs involvement of governmental and non- 3500 / p.m. through sale of vermicompost government institutions. and neem oil formulation. Application of

180 Annual Report : 2011-12 Biotechnology Programmes for Societal Development these products by women farmers in their cultivation and its significance in income own fields has also been reported to reduce generation and nutritional benefits to target use of synthetic pesticides. Approximately community. At Theni district in Tamilnadu, 900 farmers of Chamba district in Himachal a spawn production unit has been Pradesh were trained on vermicomposting established for production & distribution of and 150 farmers were provided with the spawns to the beneficiaries. Nearly 450 necessary inputs to set up vermitcomposting women beneficiaries have been trained on units in their fields. mushroom cultivation and production of value-added oyster mushroom products. A Mushroom Cultivation co-operative society of mushroom growers is also being registered to facilitate the start- In a project supported in Jammu & Kashmir, up of micro-enterprises. two mushroom training cum demonstration units were conducted in district Burdgam Aquaculture and nearly 160 women were trained on laying of spawn, casing and picking, packing, A project on development of mangrove preparation of different mushroom based based agro aqua farming for restoration of recipes. The trainees were also encouraged Mangrove ecosystem and also for to use the spent compost as fertilizer in their providing livelihood was supported at Port paddy fields and kitchen gardens. At Blair. A demonstration pond was Bangalore, training has been imparted to constructed at a farmers’ field in Indira nearly 200 rural women on Mushroom Nagar, South Andaman with provision of allowing entry of nutrient–rich water during high tide. 500 mullet (Mughil cephalus) seeds with an average weight of 10 gm. were stocked in the ponds and horticultural crops like banana, pumpkin, bottle guard were raised on the bundh. The fish grew to a mean weight of 64.54±4.54g and length of 13.09±0.46cm during four months while the culture was still underway. A total of 85 farmers have been trained on mangrove based agro- Fig. 5.6: Flush of Mushroom Fruiting at one of the beneficiary unit in J&K aquafarming.

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Women fish farmers were trained on (“Ilamathi”) on silkworm for increasing the techniques related to fish seed production silk yield enhanced the larval weight, cocoon of Indian major carps, Catla, Rohu and weight, shell weight, shell ratio and the Mrigal and also common carp at Raipur larval duration. (Chhatisgarh). Training on plankton production for spawn raising, simple method to check water quality, rearing of spawn to fry and fry to fingerling was also given to the women fish farmers.

Sericulture

About 140 women beneficiaries from Annur, Udumalpet and MGC Palayam blocks in Tamilnadu were trained on scientific methods of sericulture. Application of Fig. 5.7 : A women beneficiary applying Nesolynx thymus biocontrol agent for silkworm uzifly biofetilizers viz., Azospirillum & management Phosphobacteria enhanced the mulberry plant height (125.44cm), number of branches Livestock farming and Poultry / plant (16.90), number of leaves/ plant(19.92) and leaf yield. The leaf yield Around 200 tribal women beneficiaries from per harvest was 7154.81kg/ha/harvest when 30 viable SHGs in Senapati district of compared to 5509.49kg/ha/harvest in Manipur were trained on pig rearing, their control and resulting in an additional housing, feeding, healthcare management income of approx. Rs.2100/ha/harvest. and breeding etc. Each women beneficiary Using IPM package consisting of TNAU was given 2 weaned piglets along with botanical formulation, uzitablet and Nesolynx veterinary medicine and the provision for thymus (along with nets on windows and construction of pigsties. The piglets were doors) for the management of uzifly, larval vaccinated against “swine fever”. Farrowing mortality was reduced to a greater extent has been observed in adult sows and the and the cocoon yielded more than double beneficiaries have started to earn income (from 29.40 kg/100 dfls to 77.36 kg/100dfls) from the sale of piglets. Another project resulting in an additional income of around was supported in Parbhani district of Rs.7000/100 dfls. The use of Phytojuvenoid Maharashtra to train 250 women on goat

182 Annual Report : 2011-12 Biotechnology Programmes for Societal Development rearing by adopting osmanabadi goat,an area to be good sources of nectar and pollen improved breed. for bees.

Bee Keeping Quality Planting material

In Chamoli and Rudraprayag districts of A total of 300 farm women were trained on Uttarakhand, hill women are being raising crop with CORH 3 hybrid rice seeds encouraged towards beekeeping and they and systemic rice intensification (SRI) are being educated on the importance of techniques. An average rice yield under SRI honey, bees and other bee-products such as with hybrid was 2896 kg/acre (7.25 t/ha) bee-wax, royal jelly, bee- bread and role of which is 46.74 % higher than the variety honey bees as pollinator in increasing crop under normal method yielding only 2073 yields. A total of 40 women beneficiaries kg/acre (5.2 t/ha). The additional income have been trained and provided with Bee for the farm women ranged from Rs 5,000 boxes, colonies and necessary equipments. to Rs.15,000. Honey extracted from 29 boxes in summer season had shown an increased yield upto In Raipur and Durg districts of 2.0 kg/hive. Six honey samples were Chhattisgarh, 66 women from 4 villages analyzed for their physico-chemical were trained on maintaining seed health, properties which fulfilled Grade ‘A’ storage, processing and treatment etc. Under standards. As a part of the project, 92 bee- the project, the crops selected for quality forage plant species were identified from seed production were chickpea and three rice varieties viz., MTU 1010, Mahamaya and Karma Masuri.

In Senapati district in Manipur, Krishi Vigyan Kendra is promoting Kiwi fruit plantation among the women farmers and conducted 10 demonstration cum training programme on cultivation of organic kiwi plantation. So far, 50 hectare area has been covered with kiwi sapling and other inputs provided under the project which benefitted Fig. 5.8: Women beneficiaries trained on bee keeping in Uttarakhand around 100 women farmers.

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Value added Products PGIMER Chandigarh registered around 250 women suffering from Uterine incontinence Women (200) in Amravati district were (UI) and pelvic organ prolapse, for their educated on processing of soybean and its behavioral therapy (BT) and trained them importance in nutrition and alleviation of in Kegal exercise. It was reported that more malnutrition. Hands-on training were also than 75% women had relief in the symptoms imparted for removing anti-nutritional experienced by them. To record and monitor factors from the soybean and on preparation the incontinence severity, a pad test was of various traditional fermented products. initiated and so far it is performed with 100 In addition, there were 450 women trained patients. A workshop was also conducted at Dharwad on value addition to various on Behaviour therapy for UI at PGIMER non-forest timber products (NTFPs) for their and published a booklet on UI in Hindi, better income. English & local language and distributed among the project beneficiaries. Healthcare A project was supported on Systemic Lupus In Burdwan district of West Bengal, more Erythematosus (SLE), a prototype than 3800 women were screened for cervical autoimmune disease characterized by the cancer using visual inspection with acetic production of range of auto-antibodies and acid (VIA) method. A total of 585 VIA a diverse set of clinical phenotypes positive cases were detected showing white occurring predominantly in females than lesion in their cervix. Amongst them 47 cases males. Nearly 100 healthy age and sex of high grade precancerous lesion (CIN matched controls were enrolled. Three grade II & III) were detected and treated by codon polymorphisms of MBL genes viz. D Loop electrical excision procedure (LEEP). (52), B (54) and C (57) were genotyped by Cervical Intra-epithelial neoplasia grade I RFLP-PCR and three promoter (CIN I) lesion could be detected in 251 cases. polymorphisms (H/L, X/Y and P/Q) were A total of 41 cases of condyloma/polyp genotyped by Allele specific PCR and were also treated. The investigators are RFLP. However no difference was noted making their efforts to negotiate with the between disease severity and MBL gene Health department of the State Govt. to wild type and/or variant allele in SLE make the cervical screening programme as patients. Allele frequency of promoter region a part of the district cancer control variant alleles was observed to be slightly programme. higher among the SLE patients.

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As a part of a project supported to Kidwai of vitamin D on childhood respiratory Memorial Institute of Oncology, Bangalore, health. women with carcinoma of Cervix, Breast and Ovary were educated on importance of New Initiative balanced diet and encouraged to incorporate poly unsaturated fatty acids (PUFAs) in their In addition, the department took a new diet as a possible therapeutic substance initiative to take up a programme on capable of reducing cancer progression and ‘Women Health, Hygiene & Nutrition’ inflammatory disorders. The fatty acid under which projects will be implemented profiles in the membrane of RBCs in age at community level for the benefit of large matched women with or without cancer is number of women. The programme would also being studied alongwith the estimation cover women reproductive health needs; of fatty acids in various tumor infiltrating cancer screening, awareness and immune cells. management; chronic disorders as iron deficiency anemia, folic acid deficiency, SGPGIMS, Lucknow is pursuing a study to osteoporosis, other micro-nutrient evaluate the efficacy of Vitamin D deficiencies & nutraceuticals based supplementation in middle and last interventions, pre-natal genetic disorder trimester of pregnancy to maintain the screening and counseling etc. The projects optimum levels of maternal serum and cord will be implemented by medical institutions blood 25 hydroxy Vitamin D levels, which and governmental & non-governmental in turn would help in analyzing the effect organisations.

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185

Chapter 6

BIOTECHNOLOGY PRODUCT AND PROCESS DEVELOPMENT

INDUSTRY SCHEMES As in the earlier years, this year also three Road-shows were conducted at Kolkata, Small Business Innovation Mumbai and Kochi. The participation of the Research Initiative (SBIRI) private sector was overwhelming. Such promotional activities and also advertising The ‘Small Business Innovation Research the scheme in National dailies as well as in Initiative (SBIRI)’ is the pioneering local newspapers has resulted in a programme of the department that supports continuous flow of applications from various R&D, process & product development in industries from all the corners of the country. industry. During the present Plan Period, Under the scheme, the Department has so the SBIRI has made a mark in the biotech far received more than 900 proposals and sector. The efforts of the department has sanctioned 105 projects. Around 540 towards promotion of small and medium industries throughout the country have enterprises focusing on scientific approached the Department seeking support innovations have been appreciated by the under the scheme. State-wise response to stakeholders. the scheme is indicated in Fig 6.1.

SBIRI has helped many small and medium enterprises to establish proof-of-concept and to work on innovation R&D through its Phase-I funding through which the industries were supported primarily in the form of grants-in- aid. The scheme also supported industries towards late stage R&D resulting into process & product development through its Phase-II funding. Fig. 6.1: State-wise response under SBIRI

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During the current year the Technical Agriculture and allied areas Screening Committee (TSC) met 8 times to evaluate 114 new proposals received in The experimental protocol for assay of response to two ‘Call for Proposals’. 62 salinity tolerance in rice under simulated proposals were presented to the TSC. A conditions has been optimized by M/s. total of 40 site-visits were conducted to Bioseed Research India Private Limited, various industries to assess their Hyderabad in collaboration ICGEB, New suitability for funding. The Apex Delhi. The donor rice lines and BC1, BC2, Committee met 3 times to consider the BC3 seed from five recipient lines carrying recommendations of the TSC and to discuss gly I & gly II were tested for salinity various other policy issues regarding the tolerance in simulated conditions and out of 5 events, event B6 has consistently scheme. Based on the recommendations of displayed salinity tolerance in different the Apex Committee, the Department has genetic backgrounds with no penalty on funded 19 new proposals in different areas yield or plant growth. At M/s Rasi Seeds in biotechnology and 10 others are in Private Limited, Attur, a transformation pipeline. A three tier review process was protocol to generate transgenic cassava lines used to assess the progress in the ongoing using gene constructs containing replicase projects viz submission of quarterly RNAi genes was standardized and the progress reports by the companies, putative transgenic cassava plants hardened half yearly on-site review by Project in green house are being analyzed. Marker Monitoring Committees and yearly review free anti sense AV2 transgenic cotton plants by the TSC. Currently 52 projects are in have been developed and were evaluated operation. The details of the scheme in the field of M/s Maharashtra Hybrid and a list of the projects funded so Seeds Co. Limited, Jalna in collaboration far can be seen on the website: with IISc., Bangalore. M/s Bejo Sheetal www.sbiri.nic.in. Seeds Private Ltd., Jalna is working on Bt Brinjal expressing modified cry 1Fa1 gene Work on different projects has been and Bt Tomato & Bt Okra with cry1 Ac progressed well. Based on the reports gene. A micropropagation facility to submitted by the industries and the reviews produce 1.5 million plantlets of Jatropha undertaken by the PMCs and TSC, the major curcas L per year has been established at achievements during the year are given M/s Labland Biotech Private Limited, below: Mysore. Production of hardened net pot

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plants and poly bag plants is underway differential detection of malarial parasites done. The liquid and wettable powder has been developed by M/s Bhat Biotech formulations viz ‘Helimar’ (Helicoverpa India Private Limited, Bangalore in armigera NPV) and ‘Spodomar’ (Spodoptera collaboration with NIMR, New Delhi. Two litura NPV) have been developed and cocktails consisting of six monoclonal commercialized by M/s Multiplex Biot-Tech antibodies have been screened and Pvt. Ltd., Bangalore. ELISA kits for characterized by M/s Mediclone Biotech Pvt. detecting Cry1Ac, Cry2A, Cry1F, Chinese Ltd, Chennai and found them equivalent to fusion BT, Dow Cry1Ac have been polyclonal antisera, which is commercially developed and commercialized by M/s available for snake bite treatments. M/s Amar Immunodiagnostics Pvt. Ltd., Cadila Pharmaceuticals Ltd., Ahmedabad Hyderabad. have studied the effect of co-immunization of Mw with rabies vaccine. The adjuvant Health sector effect of Mw was found to be dose dependent for rabies vaccine and the best A production process for 500 L fermentation immune response was found with 108 Mw. batch of recombinant fuzeon under the trade Mw manufacturing process in the GMP name ‘Defuse’ for treatment of AIDS has facilities set-up for commercial production been optimized by M/s Virchow Biotech has been standardized. Development of (P) Limited, Hyderabad and the product is silkworm as a bioreactor for expression of in the clinical phase of development. In recombinant aprotinin, peptidyl amidase another project the company has and thrombin has been established by M/s commissioned the production facility for Enzene Biosciences Pvt. Ltd., Bangalore. recombinant uricase (trade name ‘Rasburicase-Tuly’) used in treatment of Industrial processes & products hyperuricemia. Toxicology studies have been completed using in-house developed M/s Bharavi Laboratories Pvt. Ltd., recombinant protein. The production Bangalore has developed a technology for process has been scaled up to 100 Lt. The production of drug intermediate (S)-3- yield of the product was 200 mg/ L and hydroxybutyrolactone from maltodextrin batch size is 3000 to 4000 vials per batch. and a value added product (S)-4-hydroxy-2- Human trials to study the effectiveness of pyrrolidinone using the enzyme pullulanase the recombinant uricase are under progress. for yield improvement and the whole HRP-II/ p-LDH based diagnostic kits for purification process was standardized

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without chromatography and distillation. designed clinical chemistry analyzers named Through this indigenous innovative as ‘Ingeniious’ is ready, consisting of 1135 technology they are able to price their parts in each and 359 among them are product at $ 500/Kg as against the Aldrich’s unique. Performance evaluation of these cost of $ 160/g. M/s India Pesticides Ltd., analyzers was also done using absorbance Lucknow has optimized the process for the standards and clinical samples. The preparation of curcumin- piperoyl conjugate. company hopes that the product would be Pure synthetic curcumin production on a priced at a very affordable rate compared large scale (4 kg/ batch with 99% purity to the imported analyzers. M/s Perfint has been achieved. Pilot scale process for Healthcare Pvt. Ltd., Chennai have dextranase production for sugar industry developed a platform of medical tool has been standardized and a product positioners for use in Image Guided ‘Dextrasol’ is ready for its further scale up Interventional Procedures as an accessory by a small industry M/s Varuna Biocell to C.T. Scan to help in performing CT Pvt. Ltd., at Varanasi. M/s Privi Organics guided diagnostic and therapeutic Ltd, Navi Mumbai has developed eight procedures like biopsies, FNAC, ablations aroma esters through the biotech route and and pain management procedures and is of developed a commercially viable technology immense use in early stage small and that can be easily scaled up. M/s Hydrolina difficult lesions in lung, abdomen and bone. Biotech Private Limited, Chennai has PIGA CT guided system is being evaluated standardized a pilot scale process for clinically in hospitals across India and the extraction of lycopene from ‘Navin’ varieties response to it has been very favorable. of tomatoes in Tamil Nadu and a Newer models of the ‘Automated commercial scale is in the process of Dispensing System’ designed indigenously establishment. Units for extraction of value and validated by M/s Customised added products from crustacean exoskeleton Technologies Private Limited, Bangalore. and coir-pith integrated zero discharge processing are being commissioned in Tamil Nadu and Kerala by M/s Pelican Biotech Bioinformatics and Chemical Labs Pvt. Ltd., Kerala. Two novel compounds, computationally Bio-instrumentation designed and synthesized by M/s Oxygen Healthcare Research Pvt. Ltd, Ahmedabad, At M/s Span Diagnostics Limited, have been demonstrated for efficacy as H3 Ahmedabad, a pilot batch of 15 newly and GPCR ligands based on preclinical data

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and PK results obtained on animal models. Biotechnology Industry The development of tools of bioinformatics Partnership Program (BIPP) by M/s LeadInvent Technologies Pvt. Ltd., New Delhi in collaboration with All India The Biotechnology Industry Partnership Institute of Medical Science, New Delhi on Programme (BIPP) an Advanced Technology design and development of inhibitors for Scheme only for high risk, transformational the treatment of tuberculosis showed technology/process development was promising results with novel compounds approved by the Cabinet in November 2008. that exerted activity against devR, which is The scheme is a government partnership a transcriptional regulator that mediates the with Industries for public support on a cost genetic response of Mycobacterium tuberculosis sharing basis for to oxygen limitation and nitric oxide exposure. • Path-breaking research in frontier futuristic technology areas having major A graphical representation on the projects economic potential and making Indian funded under SBIRI in different areas of industry globally competitive and biotechnology is given in Fig 6.2. focused on IP creation with ownerships

Fig. 6.2 Sanctioned Projects sector-wise

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by Indian industry and where relevant, has been filed. The DCGI has approved this collaborating scientists. vaccine as a two dose schedule. Phase III Clinical trials of JE vaccine has been • The development of appropriate successfully concluded by Biological E and technologies in the context of recognized has got the market license for India in the national priorities in the area of age group of >1 yr to 3year and >18 years agriculture, health, bioenergy, green to <40 years. A rapid cost-effective point- manufacturing, when the scale of the of-care diagnostic device with microPCR to problem has serious consequences for diagnose multiple diseases presently social and economic development. Malaria, Dengue & Typhoid has been developed by Bigtec Pvt. Ltd. Bangalore Calls for proposals were invited in the areas and is ready for validation. namely H1N1 vaccine development, bio- similars, affordable healthcare technologies, Service Facilities to promote Innovation anti-virals, secondary agriculture, value addition to agri-product for food and non- The facility set-up at Intas Biophar- food application, industrial scale up of maceuticals Private Limited, Ahmadabad is products and processes. now ready for use by the Academia and Industry. Services are being provided to the Under BIPP more than 700 proposals have academia at differential prices. A cGMP- been received out of which 63 projects were compliant facility for bulk-production of supported in the areas of Healthcare, monoclonal-antibodies for diagnostics as Agriculture, Energy Infrastructure and also well as therapeutic usage and microbial projects in PPP mode. Proof-of-concept antigens of diagnostic usage for providing research projects in medical biotechnology contract-manufacturing services and dealing with drug development and specialized training to biotech personnel is delivery systems, stem cell generation and being set-up at Span Diagnostics limited. clinical research have been funded and phase-III clinical trial of rotavirus vaccine Highlights of some BIPP supported has been undertaken. projects

Towards Commercialization Vaccine Development

PandyfluTM (H1N1 vaccine) have been In order to develop an affordable, Asia developed by Panacea Biotech and patent specific 15valent Pneumococcal

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Polysaccharide - CRM 197Protein Conjugate treatment of cardiovascular (CV) risk factors Vaccine studies on one India specific defined by Metabolic Syndrome (MS) aimed serotype have been completed by M/s. at increasing Resting Metabolic Rate (RMR) Tergene Biotech Pvt. Ltd., Secunderabad: has been taken up by M/s. Torrent Small scale conjugation of polysaccharide Pharmaceuticals Ltd., Ahmedabad. Phase I from this 1 Serotype with CRM-197 in studies of this molecule have been microreactor have been demonstrated. successfully completed.

Biomedical Devices Diagnostics

The study aims at developing a Amar Immunodiagnostics Pvt Ltd., comprehensive solution of planning Hyderabad has developed an ELISA based execution and control of the targeted diagnostic kit for celiac disease for detection ablation procedure by developing a of IgG and IgA specific antibodies to Tissue planning platform – for 3D visualization and Tansglutaminase (TTG). segmentation of tumor and organs, multi tool planning and ablation volume A study by M/s Abexome Biosciences Pvt. visualization; a robotic arm. The Integrated Ltd., Bangalore aims to develop antibodies planning navigation and Training Platform and assays that can be used for for Tumor Ablation has been completed. pharmacological characterization of the common biosimilar mAbs (monoclonal Clinical Trial antibodies), viz. Rituximab, Infliximab, Adalimumab, Trastuzumab and IND enabling toxicity studies of a new Bevacizumab. molecule Galnobax in rodent and non- rodent species for assessing safety for Bioenergy dermal application as well as chronic application of the product have been successfully concluded by M/s V-Life An efficient lactic acid production from Sciences Technologies Pvt. Ltd., Pune. mango kernel by Lactobacillus sp., in batch Studies are now continuing to take up fermentation process has been demonstrated phase I Clinical trial of Galnobax. by M/s SPC Biotech Pvt. Ltd., Hyderabad. In order to develop Transformational A molecule TRC150094 a novel Technology Platform for Biological Diiodothyronine (T2) analogue, for the Hydrogen, promising seedless hybrids of

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Sweet Sorghum have been identified with BIRAC will provide funding/investment for high sugar high yield by M/s Nagarjuna early and late stage, including Small Fertilizers & Chemicals Ltd. Bharat Business Innovation Research Initiative Petroleum Corporation Ltd. in collaboration (SBIRI), Biotechnology Industry Partnership with TERI has been working on a project Programme (BIPP) and ignition grant, aimed at development of process know how contract research in Industry for public for butanol production from lignocellulosic institution innovation, technology transfer biomass. and acquisition in national priority areas, promotion of entrepreneurship, incubators, parks and clusters and SME empowerment Biotechnology Industry Research measure schemes. The BIRAC will also Assistance Council (BIRAC) provide support services for IP facilitation, legal support and contracts, regulatory and The Cabinet has accorded approval for the clinical trials, mentoring and capacity setting up of “Biotechnology Industry building. Initially in order to kick start Research Assistance Council (BIRAC)” as BIRAC a pilot BIRAP (Biotechnology ‘not-for-profit’ section 25 company with a Industry Research & Development vision to stimulate, foster and enhance the Assistance Programme) was established in strategic research and innovation capabilities November 2008. of the Indian biotech industry particularly SME’s, to make India globally competitive Activities of BIRAP in biotech innovation and entrepreneurship and to create affordable products and Following specific activities to support services. research, innovation in the biotech industries have been undertaken for innovation funding, capacity building and mentoring BIRAC will operate with a core budget for programme, technology development its regular activities and recurring expenses programme, initiating technology for human resources and operational cost. acquisition, landscape analysis and BIRAC is being set up as a separate body technology mapping, support services for for supporting product innovation and policy and analysis, legal and contracts, IP providing required infrastructure and facilitation, regulatory and clinical advise etc. services at different stages of the value chain for promoting innovation and product Besides BIPP, BIRAP is equipped with the development. required staff which executed different

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programmes on capacity building. BIRAP year its activities are expected to start. All also initiated an electronic journal the programmes under I&M Sector, DBT will consortium with the help of DELCON (DBT be operated through BIRAC. Services Programme) to facilitate access to experts required at different stages of the entire and industry to over 900 journals and value chain, viz: early stage innovation scientific literature for necessary research research, product development, product back up. BIRAP is providing mentoring validation and commercialization will be programme by supporting travel and other provided under BIRAC. expenses of experts to facilitate access to important workshops, meetings and Capacity Building in IP Management conferences and associate the mandate of BIRAP with them. An IP Management and Technology Commercialization (IPM-TC) Cell has been BIRAP as a strategic partner of the Stanford supported at DBT-ICT Centre for Energy India Biodesign (SIB) programme which Biosciences at Mumbai. provides necessary facilitation for the validation and commercialization activities. Biotech Product & Process Transfer of Technology for Biofortification Development of Banana from University of Queensland, Australia is also under process. Discussions Biotech Product and Process Development are continuing with the Australian Group. programme endeavors to promote the BIRAP is facilitating the IP search, tech research efforts towards optimization and transfer agreement / contract development. scaling–up of significant leads. The BIRAP has partnered with the IP Cell in emphasis is on commercialization of the BCIL, and it is being strengthened to biotech products and processes for the provide the services to the Academia groups benefits of the society. During the year, the and Industry. Department had received 220 proposals, out of which 30 have been supported and 180 Since BIRAC has been approved by the are under different stages of evaluation. Union Cabinet it will be registered as Section Significant achievements of some of the 25 Company and activities going under projects are presented below: BIRAP will then move under BIRAC. Process of registration of BIRAC has already IIT Delhi, in the process to create PAT based been initiated. By the end of the financial control scheme for chromatography unit

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operation, create overall control scheme for purification of stevioside from the leaves of the entire process, and demonstration of the stevia with improved organoleptic property. benefits of the PAT control scheme. The Both semi synthetic and enzymatical process study envisages developing realistic PAT has been devloped in synthesis of systems for individual Bioprocessing unit glycosylated stevioside. operations that industry can implement. So far, the investigators have created critical AT IIT Bombay, work undertaken to quality attributes Granulocyte colony investigate the genetic basis behind stimulating factor of rHu-GCSF defined differential productivity in recombinant analytical scheme and seven methods have mammalian cells at a global level with a been developed for it. High throughput focus on protein secretion pathway in the resin screening protocol has been developed. endoplasmic reticulum. The investigators created a secreting CHO-K1 cell line of A work undertaken at IIT Gandhinagar, to varying productivity as a model system to eliminate use of supercritical CO2, use sub- study protein secretion. A set of 5 stable critical CO2 for precipitation and CHO cell lines have been established on stabilization of ultra-fine particles of active the protein secretion pathway. The kinetics pharmaceutical ingredients in aqueous of each cell line is studied along with gene suspensions for Pharmaceutical applications. expression and proteomic analysis. Major chaperones responsible for protein folding In a joint collaboration studies undertaken in the endoplasmic reticulum and UPR on various aspects to provide an efficient stress pathway are identified. Multivariate cost effective process for the extraction/ analysis has been performed to identify the isolation of sweet glycosides from Stevia important variables influencing productivity. rebaudiana Bertoni plant at Osmania A mathematical model is also built taking University and IICT Hyderabad. Attempts into account all the major reactions of the are made to improve the quality of the unfolded protein response pathway. sweetness of stevioside by adding at least one natural sweetener (e.g. sucrose, glucose IIT, Madras aimed at bioprocess and fructose) by glycosidation of steviosides development for the production of ethanol or by membrane separation of impurities to and polyols by Debaryomyces nepalensis NCYC obtain high purity steviosides. So far, the 3413. Different medium components are investigators have developed a méthodology screened for the optimum production of using membranes in isolation and xylitol and ethanol. Plackett-Burman

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experimental design has been used to screen pumilus for degradation of recalcitrant important medium components influencing proteins. The production of the enzyme has the production of xylitol by Debaryomyces been optimized in different modified feather nepalensis. Scaling-up the production of medium. Downstream processing of the xylitol upto 5 litre fermentor under the enzyme has been carried out with an overall optimized conditions is under progress. recovery of 84.74%. After purification of the Another group at IIT Madras is in the keratinase, the characterization of the process to characterize a recombinant purified enzyme is being carried out along putative acetyl xylan esterase from the with its evaluation for degradation of yeast thermostable bacterium, Thermotoga maritima prion clone (Sup35NM). for potential industrial applications.

IIT Guwahati, characterized the industrially Collaborators from Lady Doak College, important proteases from selected protease Karunya University, Vision Research producing bacteria isolated from Foundation, and Madurai Kamraj University environmental samples of north-east India. Chennai are developing the matrices using Novel alkaline proteases from Brevibacillus short and medium chain length PHA sp.AS-S10-II and P.tezpurensis sp.nov.AS-S24- produced by Pseudomonas sp. LDC-5. PHA II have been isolated. An alkaline â- production has been optimized purified and keratinase from B.licheniformis AS-S24-I strain characterized. Biocompatibility of PHA has been isolated and its application in based matrices has been established with laundry detergent has been formulated. A 3T3 mouse fibroblast. Cytotoxicity process optimization for degradation of raw assessment of purified PHA and PHA based chicken feather using alkaline â-keratinase matrices is carried out to ascertain the non- from B.licheniformis AS-S24-I strain has been toxic property of PHA. In vitro analysis of evaluated. matrices for the growth of continuous cell lines of human origin are in progress. Shri AMM Murugappa Chettiar Research Isolation of stem cells from human cornea Centre, Taramani, Chennai are aiming at is in progress and primary cultures of mass cultivation of the fruiting bodies of corneal limbal stem cells are being different strains of Ganoderma lucidum at standardized. different climatic conditions, validation of nutraceutical properties in reputed / University of Delhi is optimizing the process accredited National and International for Keratinase production from Bacillus laboratories leading to formulation of

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Ganoderma powder as potential products of permeability in patients with active nutraceutical importance. ulcerative colitis in a double blind randomized placebo controlled trial is Gulbarga University is attempting to ongoing in PGIMER, Chandigarh. A total of develop dietary Nucleotides from 90 patients have been screened and 15 have Sugarcane for Therapeutic Applications. The been recruited in the trial so far. Two highest concentration of nucleic acid has groups of patients received 450 CFU of been observed in saccharum officinarum, VSL#3 and 3600 CFU respectively and each Glycin max, Phasleolus vulgaris, Phasleolus of these groups has a placebo treated control aureus, Phasleolus mungo, Saccharomyces group. crevisiae. Research on small intestinal and whole gut ICGEB, Delhi has undertaken work on in metagenome in patients with celiac disease vitro biosynthesis of antimalarial drug is progressing at AIIMS and NCCS to study artemisinin via metabolic engineering of BY- the metagenome of duodenal biopsies and cells. whole gut metagenome in the stool of the treatment naïve patients with celiac disease, Biotechnological Approaches for patients on gluten free diet for atleast one Food and Nutritional security year, first degree relatives of celiac disease and controls. During the year emphasis was given to understand the beneficial role of probiotics ARI, Pune is working to develop a process for human health, food safety issue for increasing resistant starch in selected addressal, developing novel food products food materials and to assess their pre-biotic & processes, rapid detection kits for GM and anti-inflammatory potential through in foods, utilization of agricultural residues for vitro and in vivo models. Ten cereals and obtaining value added products and low pulses were subjected to retrogradation and cost nutrient food supplements. three of them showed significant increase in resistant starch. Probiotics for human health For enhancement of innate Mucosal Work on the effect of probiotic on reducing immunity probiotics (Lactobacillus acidophilus, intestinal inflammation, inducing clinical Bifodo bifidum and Bacillus clausi) were used remission and restoring intestinal to treat murine macrophage RAW 274.6,

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human monocyte THP-1 and intestinal growth of all pathogens tested except Caco2 cells. Microarray studies of mRNA Pseudomonas and Bacillus cereus. extracted from probiotic treated cells indicated that approximately 7000 entities Probiotics for treatment of Bacterial showed 2 fold and higher changes in terms vaginosis women with recurring episodes of expression. of vaginosis or vaginitis whose vaginal pH is above 5 were enrolled in the clinical trial NDRI is working on to understand the which is being conducted at AIIMS and Sir interaction of probiotics bacteria with innate Gangaram Hospital, New Delhi. The trial and adaptive immune system to alleviate employs BASANT (a polyherbal microbicide the immunogical reactions in a neonate and consisting of curcumin, purified extracts of aged animal model. Three probiotic amla, purified saponins, aloe vera and rose Lactobacillus strains (L.casei, L.acidophilus and water) dispensed either as a tablet or as L.helviticus) were selected on the basis of capsule which is used every night for 14 probiotic attributes and used for preparing days, initially to cure vaginosis or fermented milks. Preliminary results indicate vaginitis. that mice fed with milk fermented with L.helveticus recorded remarkably higher Detection of Genetically Modified Foods lymphocyte proliferation index compared to (GMOs) and Food Products control and other probiotic fermented milk groups. Research at NBPGR, New Delhi is constructing a system of 96 well pre spotted Probiotic for fetal immune programming an plates for the individual detection of targets encapsulated combination of probiotic and allowing the simultaneous identification of prebiotic is being studied to see for any GM events by the use of event specific impact on fetal immune programming. primers and probe combinations for Among 18 Lactobacillus strains tested, detection of GMOs. Transgene/ promoter/ Lactobacillus paraplantarum 321 and marker/endogenous gene specific simplex Lactobacillus helviticus 194 inhibited the PCR based detection protocols have been growth of all pathogenic bacteria under test developed for six GM maize events and conditions while, Lactobacillus helviticus 194 four stacked GM maize event. Twelve GM strain showed susceptibility to Proteus, E.coli Events, 5 Cotton Events and 7 maize évents ATCC and Pseudomonas species. along with their endogenous genes, were Bifidobacterium bifidum 231 also inhibited the validated on the ready-to-use multi-target

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analytical system with specific primers and Functional Foods probes. Event-specific Real time PCR protocols for Bt brinjal with cry1Ac, cry1Ab Development of Fermented functional and cry1Fa genes have been developed. foods from papaya

Studies are underway to isolate, characterize Addressal of Micronutrient and and evaluate the fermentative ability of Macronutrient deficiencies endophytes of papaya fruit from four economically important varieties. The Studies on development of multi- phylogenetic analysis based on the 16S micronutrients fortified milk are underway rRNA sequence revealed that the isolated for the assessment of the potential of toned endophytes are genetically distinct and milk as a vehicle for iron and vitamin A cluster as discrete clades in the dendrogram. and calcium and vitamin D. The Fermentative ability of the isolates was development of micronutrient fortified milk assessed and Bacillus niacini isolated from would be helpful in iron deficiency anemia seeds of “Bangalore” variety utilized the in particular. BIBCOL has developed a fruit sugars and improved the antioxidant product consisting of a mixture of seven potential of the fermented product. The minerals and thirteen vitamins as per WHO findings provide evidence that different guidelines in a sachet aimed for treatment parts of papaya fruits harbor an array of of severely malnourished children. bacterial endophytes that could be important agents in attributing the high nutritive status Development of Diarrhoea Management to the fruit. These fruit isolates could serve Combo Kit as potent microbial cocktails for developing value added fermented products.

A combo kit comprising of zinc tablets (14 Bioactive Peptides tablets) and two sachets of ORS has been manufactured by BIBCOL. Scaling and Toothpastes containing 4% Caseino- automation of Zinc tablet production has phosphopeptides (CPPs) exhibited higher been set up at BIBCOL. 30 lakh diarrhoea efficiency than those containing 3% CPPs in treatment kits have also been supplied to comparison to flouridated and control high burden North Eastern states for large toothpastes. An in situ study on college scale demonstration. students, on remineralization of enamel

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lesion using sugar free chewing gums Human Resource Development in Food incorporated with 3% CPPs showed greater Science and Technology through Integrated area of remineralization as compared to Master’s and PhD programme control chewing gums. A study on experimental rats for nutritional quality of Integrated Masters and PhD programme was weaning foods(WF) incorporated with initiated by DBT in Anna University hydrophilic, hydrophobic CPPs and control Chennai; Banaras Hindu University, WF without CPPs, revealed an Varanasi; IIT-Kharagpur and University of enhancement in ‘bone mineral density’ in Kashmir, Srinagar. The research priorities weaning food with hydrophilic CPPs in the above 4 institutions focus on fluid followed by those with hydrophobic and foods including dairy foods, fermentation the control WFs. technology, vegetable processing technology, processing of foods of plant and Preparation of novel reduced calorie fats meat origin, food processing engineering, fermentation and bio-processing Two structured lipids (SL-1 and SL-2) were engineering, extension of shelf life of food prepared by inter esterification reaction items, fortified ready to eat products. using lipase enzyme. Both the structured lipids contained significant amounts of New initiatives behenic acid and linoleic acid. The serum triglyceride levels were lowered Medical Management of Children significantly in rats fed SL- 1and 2 compared suffering from Severe Acute to that in rats given sunflower oil. The Malnutrition caloric value of SL- 1and 2 were lower in comparison to sunflower oil. The differential Sever Acute Malnutrition without calorimetry scanning studies indicated complications (SAM) are an acute state of similarities in thermo physical properties severe wastage in under 3-yr age children, between bakery fats and SL- 1. Bakery where the body mass is retarded products, such as cakes and biscuits were particularly in relation to height. SAM is an prepared by replacing bakery fats by important cause of morbidity and mortality structured lipid. Low calorie bakery in children below 5 years of age in India products which are free from trans fats where approximately 8.1 million children could thus be prepared using structured are estimated to suffer. Up to 15% under lipids. the age of five, children with SAM require

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inpatient management because of medical activities involving GE Organisms and complications. The remaining 85% (without contained/confined field experiments of GE medical complications) can be managed crops, insects and trees. During the year, through a community and or home based RCGM has taken several new initiatives for care approach. the promotion of r-DNA technology in the fields of agriculture and pharmaceuticals An alliance has been formed among and provided technical advice to GEAC to Departments of Health Research (DHR) and enable the facilitation of decision making Biotechnology (DBT), and Ministry of Health on GMOs/ living modified organisms and Family Welfare of the Government of (LMOs) and products thereof for releasing India to support research to generate them into the environment and for evidence for development of practical and subsequent commercial use. scalable regimens to medically rehabilitate children suffering from SAM without serious During the year, the RCGM considered complications at home/community level about 800 applications in twelve meetings and/or at peripheral inpatient facilities. in the areas of agriculture, pharmaceuticals and industrial products for import/exchange The department has taken an initiative for of GE materials including transgenic seeds, identification of children in the community gene constructs, plasmids, vectors, and who have SAM without complication for GMOs/ LMOs; conduct of pre-clinical which the proposals were invited in joint toxicity studies on innovative new drugs collaboration with the Departments of (IND)/similar biologics; evaluation of pre- Health Research and Ministry of Health and clinical study data on IND/similar biologics, Family Welfare of the Government. conduct of Biosafety Research Level 1 (BRL1)/ event selection trials in confined Biosafety Issues conditions on several GE crops of new genes or events developed by public/private In compliance with the Rules-1989 of institutions/companies for generation of Environment (Protection) Act, 1986 (EPA- biosafety data; and conduct R&D in 1986), the Department has reconstituted the pharmaceutical and agricultural areas. R&D Review Committee on Genetic Manipulation activities are continuing on various other (RCGM) to evaluate, approve and monitor crops like rice, okra, brinjal, mustard, the safety related aspects of new and tomato, cabbage, cauliflower, ground nut, ongoing rDNA projects and research pigeon pea, chick pea, cowpea, finger

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millets, sunflower, soybean, bamboo, castor, public/autonomous institutions. Information wheat, black gram, black pepper, chilies, on the healthcare products approved by onion, papaya, rubber etc. Eight public/ RCGM for conduct of pre-clinical toxicity private institutions/seed companies were studies during 2011 is given in Table-6.2. permitted to conduct confined field trials of Based on the pre-clinical study reports, 18 five GE crops viz., brinjal, cotton, rubber, rDNA products developed by 11 private/ corn and mustard containing new genes/ public institutions & companies were events with the approval of RCGM & recommended by RCGM to DCG(I) for GEAC. Transgenic tree species like rubber, appropriate phase of clinical trials. Table and transgenic insects like silk worm and 6.3 gives the details of rDNA products mosquitos are on fast track of development. recommended by RCGM to DCG(I) for List of approvals accorded for conduct of appropriate phase of clinical trials. confined field trials of BRL-1 on GE crops developed by public/private institutions/ The department continues to receive seed companies within the country is given applications from institutions working with in Table-6.1. Eleven Central Compliance GMOs for constitution of Institutional Committee (CCC) teams constituted for Biosafety Committees (IBSCs). Twenty seven monitoring the BRL-1 confined field trials (27) new IBSCs have been constituted at on GM crops conducted by private/public various public-funded institutions, sector institutions & companies. Department universities, private R&D institutions and participated in ‘Event based approval industries involved in rDNA research. After mechanism (EBAM)’ for commercialization due diligence to the comments received from of transgenic Cotton Hybrids, Standing government/ private institutions and Committee constituted by Ministry of stakeholders the revised formats for Environment & Forests. Based on the intimating/ requesting IBSC/ RCGM for approval of the Standing Committee 142 import/ export/ exchange GMOs/ LMOs transgenic cotton hybrids expressing four and product thereof, and to conduct pre- approved events were recommended to clinical toxicity studies of recombinant State Agriculture Departments for products, biosafety research trials on GE commercialization under EBAM. crops under confined conditions and to carry out research and development. In order to In the pharmaceutical sector, 26 rDNA strengthen the Indian Biosafety Regulatory products were approved for conducting pre- System, several consultative meetings with clinical toxicity studies by 16 private/ various stakeholders were held. Biology

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Documents on Cotton, Okra, Maize and Rice and “Indian GMO Research Information with basic and useful information were System (IGMORIS)” (http://igmoris.nic.in). developed for the benefit of the applicants These websites also facilitate tracking of conducting Biosafety research trials under regulatory clearances on applications to contained/confined conditions. Regulatory RCGM and e-monitoring of IBSCs on guidelines for recombinant bio-therapeutic personalized web features. Based on the products, formulated on “Similar Biologics”, advancements in the field of agriculture & are under evaluation by other national pharmaceutical areas on GMOs/ rDNA regulatory bodies for harmonization and research globally, necessary improvements implementation. Based on the RCGM are being incorporated in the Biosafety recommendations, four sub-committees have regulatory system in the country. been constituted by the RCGM to formulate/ revise (1) the present set of guidelines The Industrial growth around the world is available for conduct and monitoring of steered by technological innovation through confined field trials along with devising new research & development. To promote the crop specific guidelines; (2) preparation of R&D activities in Biotechnology, 18 private environmental risk assessment (ERA) research institutions have been guidelines for ERA of genetically engineered recommended to Department of Scientific crops; (3) Biosafety guidelines to conduct and Industrial Research for recognition of and monitor Confined Research Trials their In-house Research & Development (CRTs) on genetically engineered (GE) Units. Products and services of Insects; and (4) Biosafety guidelines to biotechnology origin were also promoted conduct and monitor Confined Research by communicating department’s view on Trials (CRTs) on genetically engineered (GE) fixation of standard input/ output norms trees. (SION) for 12 export products; and no objection certificates (NOC) for 14 cases for As the knowledge in the modern export/ import of biotechnology products biotechnology is ever expanding, efforts are to Directorate General of Foreign Trade being made to update with the latest (DGFT). Comments/ suggestions have also information and also modifications, been provided to various ministries/ amendments etc. in the guidelines from time departments for commercial release of to time for the stakeholders through two biotech products, compulsory licensing, dedicated dynamic & interactive web sites foreign direct investment, international on “Biosafety” (http://dbtbiosafety.nic.in) commerce and other relevant issues.

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Table-6.1: Genetically Engineered crops approved for conduct of confined field trials of BRL-1 by the private/public organizations and seed companies during 2011

S. GE Crop Institute/ Industry Transgene/ s No. • Maharashtra Hybrid Seeds Co. Ltd., Mumbai cp4epsps 1 Cotton • JK Agri Genetics Ltd, Hyderabad cry1Ac & cry1Ec • Bayer Biosciences Pvt. Ltd., Gurgaon 2mepsps • Pioneer Overseas Corporation, Hyderabad cry1F, cp4epsps & PAT 2 Corn • Syngenta Biosciences Pvt. Ltd., Pune cry1Ab & 2mepsps (Bt11 x GA21 event) • Centre for Genetic Manipulation of Crop Plants (CGMCP), University of Delhi South Campus, 3 Mustard New Delhi bar, barnase and barstar • National Research Centre on Plant Biotechnology (NRCPB), New Delhi Osmotin • 4 Sorghum Directorate of Sorghum Research, Hyderabad cry1B (NRCSCRY 1B, event-19)

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Table-6.2: List of rDNA products (Healthcare) approved for Pre-Clinical Toxicity studies during 2011

S.No. Products Institute/Industry

1. • Pegylated Recombinant Human Granulocyte Bio Genomics Ltd, Mumbai Colony Stimulating Factor (PEG-rh-GCSF)· • Recombinant Human Interferon alpha 2a (rh-IFNá- 2a) • 2. Pegylated Recombinant Human Interferon alpha 2a (Peg-rh-IFN-2a) Avesthagen Ltd., Bangalore • Recombinant Human Insulin Analog (Insulin Aspart; B28Asp-Insulin) Cadila Pharmaceuticals Ltd., 3. Ahmedabad • Recombinant Human Insulin Analog (Insulin Glargine; A21Gly, B31Arg-B32Arg-Insulin) Virchow Biotech Private • Tenecteplase: Recombinant Fibrin-Specific Ltd.,Hyderabad Plasminogen Activator • Trivalent Seasonal Influenza VLP Vaccine Sudershan Biotech Ltd., 4. Hyderabad • Pegylated Recombinant Human Granulocyte Colony Stimulating Factor (Peg-rh-GCSF) Shantha Biotechnics Ltd, 5. • Rabies G VLP vaccine Bangalore • Recombinant Human Granulocyte Colony Intas Biopharmaceuticals Ltd., 6. Stimulating Factor (rh-GCSF) Ahmedabad • Recombinant Interferon beta-1b (rh-IFNâ-1b) 7. • Recombinant HPV Vaccine Lupin Ltd., Pune • Etanercept: TNFá Receptor-Fc fusion protein FDC Ltd., Mumbai • 8. Bevacizumab: Recombinant Humanized Anti-VEGF Monoclonal Antibody Gland Pharma Limited, • Hyderabad 9. Etanercept: Recombinant TNFá Receptor-Fc fusion protein Inbiopro Solutions Pvt. Ltd., • 10. Filgrastim: Recombinant Human Granulocyte Bangalore Colony Stimulating Factor (rh-GCSF) • Teriparatide: Recombinant Human Parathyroid Symmetrix Biotech Pvt. Ltd., 11. Hormone (1-34) (rh-PTH:1-34) Chandigarh • Teriparatide: Recombinant Human Parathyroid 12. Reliance Life Sciences Pvt. Ltd., Hormone (1-34) (rh-PTH:1-34) Mumbai • Recombinant Streptokinase (SK) · 13. Recombinant Clot Specific Streptokinase (CSSK) Serum Institute of India Ltd., Pune • Darbepoetin alpha 14. · Infliximab: Recombinant Chimeric Anti-TNFá Bharat Biotech International Monoclonal Antibody Ltd., Hyderabad 15. • Pneumococcal Conjugate Vaccine Cadila Healthcare Ltd., • 16. Polysialylated Erythropoietin Ahmedabad

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S.No. Products Institute/Industry • 1. Darbepoetin alfa Hetero Drugs Ltd., Hyderabad • 2. H1N1-09 Influenza VLP Vaccine Cadila Pharmaceuticals Ltd., • Ahmedabad 3. Recombinant Enfuvirtide • Rituximab: Recombinant Chimeric Virchow Biotech Private Ltd., Anti-CD20 Monoclonal Antibody· Hyderabad Pegylated Erythropoietin Intas Biopharmaceuticals Ltd., • Filgrastim: Recombinant Human 4. Ahmedabad Granulocyte Colony Stimulating Factor (rh-GCSF) USV Ltd., Mumbai • Pegylated Recombinant Human 5. Lupin Ltd., Pune Granulocyte Colony Stimulating Factor (PEG-rh-GCSF)· Teriparatide: Recombinant Human Parathyroid Hormone (1-34) (rh- PTH:1-34)

• Recombinant Live Vibrio cholerae VA National Institute of Cholera & 6. 1.4 Vaccine Enteric Diseases (NICED), Kolkata • Clot Specific Streptokinase 7. • Symmetrix Biotech Pvt. Ltd., Peg-Filgrastim: Pegylated Chandigarh 8. Recombinant Human Granulocyte Colony Stimulating Factor (PEG-rh- GCSF)· Trastuzumab: Recombinant Humanized Anti-HER2 Monoclonal Reliance Life Sciences Pvt. Ltd., Antibody Bevacizumab: Recombinant Mumbai Humanized Anti-VEGF Monoclonal Antibody · Infliximab: Recombinant Chimeric Anti-TNFá Monoclonal Antibody · Darbepoetin alfa

• Rituximab: Recombinant Chimeric 9. Anti-CD20 Monoclonal Antibody Cadila Healthcare Ltd., Ahmedabad • Pegylated Recombinant Human 10. Granulocyte Colony Stimulating Biocon Ltd., Bangalore Factor (PEG-rh-GCSF)· 11. Trastuzumab: Recombinant Humanized Anti-HER2 Monoclonal Antibody

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to industry and further commercialization. Patent Facilitation Cell The following six patents have been granted during the year 2011-12 The main objective of Biotechnology Patent Facilitating Committee (BPFC) of the 1. Oligonucleotides for detection of Department of Biotechnology (DBT) is Leishmaniasis and methods thereof creation of awareness and understanding (Patent no. 246347/India) relating to intellectual property rights (IPR) among students, scientists and faculty of 2. Diagnostic kit for detection of Pulmonary colleges, universities and research institutes and extra pulmonary Tuberculosis through workshops, seminars and (Patent no. 7888037B2/US) conferences. BPFC also assists the investigators in patent filing in IPO, USPTO 3. Novel Polymer for solid phase peptide and other countries. All patent applications synthesis and process for preparation on inventions pertaining to Life Sciences thereof (Patent no. 248550/India) and Biotechnology received in the Department are subjected to a rigorous 4. An Oligonucleotide primer pair for scrutiny. Based on merit, department detection of Mycobacterium tuberculosis provides administrative and financial using the primer (Patent no. 248630/ support for patent filing in India and other India) counties. The patent filing is done through National Research Development Corporation 5. Process for producing a Biopesticide (NRDC), New Delhi. BPFC also plays an composition containing Trichoderma important role in transfer of technology to harzanium and Pseudomonas fluoresces industry and its commercialization. (Patent no. 7923005B2/US)

During the period, 17 patent applications 6. Process for the preparation of Herbal were process for filing with IPO, USPTO Extract from the Fern Cheilanthes farinose and in other countries through NRDC. Seven effective against liver diseases (Patent technologies are under process for transfer no. 250038/India)

208 Chapter 7

BIOTECHNOLOGY INFORMATION SYSTEM NETWORK

Biology in the 21st century is being infrastructure, databases and human transformed from a purely lab-based science resource who could transform the data into to an information science as well. Over the meaningful information, understanding and past few decades, major advances in the product development. The BTISnet of DBT field of molecular biology, coupled with is promoting these activities efficiently. advances in genomic technologies, have led Major such activities are discussed to an explosive growth in the biological herewith. information generated by the scientific community. The sequencing and mapping BTISnet in a Nutshell of Human Genome and hundreds of other genomes has, in turn, led to an absolute BTISnet a potential scientific network in requirement for computerized databases to the country comprises of more than 165 store, organize, and index the data and for institutions. The network embraces state of specialized tools to view and analyze the art infrastructure, human resource data. development and exhibited capability in carrying out intensive research and The Bioinformatics is attaining greater development activities in bioinformatics significance in the life sciences research and and computational biology. Based on the industry and hitherto unexplored areas of outcomes of BTISnet a compendium on biology. Bioinformatics, computational and “Research publications in Bioinformatics systems biology are data driven and and computational biology from India” was algorithm intensive research areas are released on 3rd February, 2012 listing more becoming important. In the field of than 3000 peer reviewed research bioinformatics, the life sciences sector is publications in these areas. Centers of now focusing on analysis and interpreting BTISnet were networked through high voluminous data generated through speed leased line connectivity earlier and biological research. Biological research has now some of them are being networked become more and more data intensive and through National Knowledge Commission requires advanced Bioinformatics (NKN) network. Skilled human resources

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are being promoted through the long term & 4th February 2012 at Shri Mata Vaishno and short term courses and trainings. One Devi University, Jammu with a focal theme noticeable good thing is happening that of “Bioinformatics in 21st Century- Looking the experimental researchers are now keen ahead”. Prior to this a National Symposium to adopt bioinformatics approach for the on “Bioinformatics: Challenges in the Post- biotechnology research and the Genomic era” was organized by the bioinformaticians are now getting fair University of Jammu on 2nd February 2012. opportunities to work with hard core Three important programs of DBT on DBT’s experimental biologists. The BINC exam e-Library Consortium (DeLCON), which is considered as highly stringent Conference, Travel, Exhibition and Popular national exam is picking up well and 35 Lectures (CTEP) and the Innovative Young candidates have been qualified in this year. Biotechnologist Award (IYBA) are being Eight new BIF centers have been added to very effectively coordinated by the Apex the BTISnet and in fact the new generation BTIC in DBT. The location of the centres is bioinformatics centers are doing depicted in the Map below (Figure 7.1). exceptionally very good and they brought lot of experimental component to the bioinformatics. NEBInet which comprises of more 25 bioinformatics centers in North East states has opened up great opportunities in biotechnology for the North East Region of the country. Through this network it is now much simpler to generate and implement programs for this region and outreach has become much easier. Several new programs like Biotech hubs, overseas associateship, Twinning R&D etc. are being implemented with the support of NEBInet. Three major consortium projects on Bioinformatics in TB, Rice and Mango have been shown excellent progress during this period. The XXIII Annual BTISnet Coordinators meeting for the year 2011-12 was organized on 3rd Fig. 7.1: Map showing the locations of BTISnet Centres

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The Centre also has Cambridge structural Centres of Excellence (COE) in database (CSD) which contains more than Bioinformatics 586,977 small module structures. 68 Project Assistant, 23 Project trainees and 98 summer Six CoEs in Bioinformatics and trainees have been trained both at CoE and Computational Biology have been the interactive Graphic Facility. 23 high established as part of BTISnet. These Centres impact publications have been published are well equipped with State of Art during this year. Bioinformatics infrastructure to support research within the Institute as well as The CoE at JNU, New Delhi is a part of the neighbouring institutions. The CoE at Bose School of Computational and Integrative Institute, Kolkata is specialising in the areas Sciences, with a major objective of like genome analysis, regulatory RNA stem development of human resource through cells and genomics and structural teaching and research in the frontier area of bioinformatics. It provides projects to computational biology, bioinformatics and students undergoing Post Graduate courses systems biology. The Centre is also working from your large number of institutions and on Mycobacterium tuberculosis, through TB universities. In 2011, 16 important research Consortium project supported by DBT and papers have been published by the Centre. the Centre is also engaged in Leishmania The CoE at IISc Bangalore has shown a and Plasmodium falciparum. The Centre under paradigm shift in the focus of the centres the CoE Umbrella conducts M. Tech course activities which is now directed towards in Bioinformatics, Computational and strengthening integrated research Systems Biology. In addition, the Centre also programmes in several areas of conducts BINC Examination since 2010-2011 Bioinformatics with a long term goal of onwards. 27 Peer reviewed research developing computational modules of publications have been published by this Biological macro-molecules and cellular Centre during the reporting period. The CoE processes at different levels of abstraction at Madurai Kamaraj University, Madurai is to aid new hypothesis generation, new ways specialising in the areas like structural of research in Biology and in generating Bioinformatics, proteomics data mining and applications, opportunities in drug and computer aided drug design. Towards vaccine discoveries. The Centre hosts a manpower development the Centre runs major mirror server for structural network M. Sc. Computational Biology classification of protein (SCOP) structures. course along with Anna University, Chennai

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and Pondicherry University, Pondicherry. 2010-11 this Centre was organizing the BINC The Centre is having collaborative research examination. The Centre has developed 3 with international and national institutions major databases namely viral protein in the field of Bioinformatics such as structural database, antigen antibody Wiseman Institute, Israel, University of Utah, genomics and viral genome resources. 12 USA, Aravind Eye Hospital, Madurai, important papers have been published by NCBS, Bangalore and AIIMS, New Delhi. the Centre during this period. The CoE They conduct research with them in the namely Super- computing Facility for areas like E. Coli, fungal kinetics, Bioinformatics (SCFBio) at IIT Delhi provides classification of proteins, M. tuberculosis and super-computing facility for the institute, in-silico drug design. More than 20 papers researchers and scholars. Centres are also have been published by the Centre during utilising its resources both hardware and this year. software packages developed by the Centre. The website showing software for predicting The Centre at University of Pune, Pune DNA-Drug interaction strength has been conducts M. Sc. in Bioinformatics and before shown as Figure 7.2.

Fig. 7.2: Software for predicting DNA-Drug interaction strength

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various Institutions/Universities and are Bioinformatics Infrastructure working along with specialized areas of Facilities (BIF) For Biology Bioinformatics. At one point of time these Teaching through Bioinformatics (BTBI) Centres were considered as user Centres of Bioinformatics and over the period of time To promote the biology & biotechnology the Sub-DICs also have shown their teaching through bioinformatics, a scheme capabilities in training the people as well was launched recently namely as development of information resources in Bioinformatics Infrastructure Facility (BIF) the form of Databases. Many Centres of this to promote innovations in the area of level are doing good bioinformatics R&D Biology & Biotechnology among the and have published number of Institutions/ Universities/ Colleges all over Bioinformatics peer reviewed Research the Country. The scheme is designed to Publications. expose teachers, scientists and students to the real-world of science and the use of North Eastern Bioinformatics bioinformatics in solving hard core Network (NEBInet) biological problems. Several sites provide free access to biological information A separate NEBInet has been established resources to promote advanced biology and by including 27 Bioinformatics centers in develop human resource to undertake the North Eastern region of India as a part challenging research in the field of modern of BTISnet. These Centres are mainly located biology. The centre can use the lecture at various universities, colleges and materials, video clippings, demonstrations, institutions to promote modern scientific tutorials and online facilities to cater the need of present generation in modern research communication among the scientific teaching and innovation. Ninety nine community, sharing of information and help educational institutions have so far been in initiating collaborative R&D activities in supported under this scheme and some various fields of life. Being a North Eastern more are in pipeline. States Centre’s, these centers are given special emphasis for an overall development Sub-Distributed Information Centre in the Country and are linked with all other BTISnet Centre. During the current year two Fifty centres of this category are as part of centers were established in the North BTISnet. These Centres are located at Eastern Region.

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Pondicherry University, Pondicherry and Human Resource Development Anna University, Chennai initiated a in Bioinformatics, Computational Network programme on higher education and Systems Biology in “M.Sc. Computational Biology” on consortium basis. These places are utilizing Bioinformatics is an emerging the resources through video conferencing interdisciplinary area of biotechnology and and virtual class room approaches. The encompasses systematic development and program envisages creating of a strong application of IT solutions to handle computational and experimental basis to biological research problems. Areas such as bioinformatics education at the post proteomics, genomics, combinatorial graduate level. The other universities i.e. i) chemistry, statistics, nanotechnology, JNU, New Delhi ii) Pune University, Pune spectroscopy and structural and and iii) Calcutta University, Kolkatta are computational biology will have increasing continuing M.Tech., M.Sc. and Post Graduate applications of Bioinformatics in days to diploma courses in bioinformatics, come. To handle all these biological research respectively. This year more than 70 students problems, it requires highly trained graduated from these programs. manpower to deal molecular biology and application of software tools. The department had accorded this area high Ph.D. Program in Bioinformatics priority and has introduced several innovative educational activities to meet the The COEs of BTISnet including the super present requirements including several long- computing facility at IIT, New Delhi are term and short term educational programs running Ph.D. programs in Bioinformatics to address this gap. The details are as to meet the huge requirement for high end follows. human resource in Bi3oinformatics & Computational Biology and training. M. Sc. Network Program, M.Tech & Advanced P.G. Diploma Courses in Short Term Training Programs Bioinformatics Basic understanding and hands on The objective of this network programme is experience in the area of Bioinformatics is to share the expertise of teachers as well as provided to the researchers and students, the resources which are created by the by each of the BTISnet Centre by conducting BTISnet Centres. The MKU, Madurai, one or more short term training programmes

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each year. A schedule of the training for BINC JRF fellowship and register for programmes conducted by BTISNet Centres PhD in Bioinformatics & computational is published in the form of annual training biology, the candidates must possess a calendar each year by the Department. The Master’s degree in Science or Technology BTISnet centres organized more than 100 or Medicine. The exam employs a three-tier short-term training during the year 2011-12 system including an objective, subjective so far. and practical examination. All the candidates who register for the BINC examination Bioinformatics National appear for Paper I. Those who secure 40% Certification Examination (BINC) marks in paper I are eligible to appear for Paper II, which is subjective type and Paper The BINC examination was introduced in III, which is hands-on practical examination. 2005 by the Department of Biotechnology (DBT), Government of India to certify All successful candidates are awarded with professionals in the area of Bioinformatics certificates of proficiency in Bioinformatics, as the subject has emerged as an a cash awards of Rs. 10,000 to each of the independent discipline over the years and top ten candidates and research fellowships is assuming an increasingly important role (DBT-BINC-JRF) to carry out research in the Life Sciences research in the post- leading to Ph.D. in the area of Bioinformatics genomic era. The University of Pune has in any of the recognized Indian coordinated the BINC examination on behalf Universities/Institutes. The fellowship is at of DBT during 2005-2010. The BINC par with NET, GATE, BETnational Exams. National Coordination committee is the JNU, New Delhi is conducting the BINC driving force in setting and maintaining high exam from 2011 onwards. So far, 85 standards of the BINC examination. The candidates have qualified the BINC and out examination is conducted at eight centers of them 15 are availing the fellowship. and has gained in popularity over the years as evidenced by the number of candidates R&D in Bioinformatics and that appeared for the examination and the Computational Biology number of candidates that qualified for certification. (http://binc.scisjnu.ernet.in/). During the year, the department has Any science graduate with or without formal received more than 50 R&D projects in the training in Bioinformatics can appear for area of bioinformatics and sanctioned new this examination. However, to be eligible 12 R&D projects. Besides that the

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department also continued support to eight characterization of SNPs in Wheat (Triticum ongoing projects on Bioinformatics and Cell aestivum L.) and haplotype structure engineering generated through Indo-Japan determination using Next-Generation Collaboration and 117 new projects through Sequencing Data, Drug Target the twining program for North Eastern Identification in Infectious Disease through States. The projects were supported in the Molecular Simulation an Biochemical area of Molecular Dynamics Studies of the Network Modeling and Online tool Homology Model of CYP1A1, Structure development for extraction of diseased Based Drug Design and Virtual Screening proteins and pattern database creation. of Potential Ligands that Modulates the Biological Function of CYP1A1, Consortium Projects on Development of Computational Mosquito Bioinformatics borne viral data and potential antiviral drugs by isolation of arboviruses from Two major consortium projects viz. (i) TB- female mosquitoes and in silico screening bioinformatics and (ii) Rice bioinformatics for immungenic membrane protein and are running smoothly. TB Bioinformatics II modeling of suitable antivirals including phase has been sanction this year. In TB- in vitro confirmation, Study of some bioinformatics seven major institutions are important signalling and metabolic partners, and, in rice bioinformatics eight pathways in T-cell and glioma, role of institutions namely NBPGR, New Delhi, protein complexes and protein protein NRCPB (IARI), New Delhi, CRRI, Cuttack, interaction network in eukaryotic protein IGKV, Raipur, DRR, Hyderabad, CSSRI, evolution, understanding Systems Biology Karnal, IAS, Varanasi and UDSC, New of a Rhizobacterium, Azospirillum brasilense Delhi are the partners. Rice Bioinformatics by in-silico and in-vitro study of the project has entered in its second year of cascades and Networks of Sigma Factors, implementation and has shown good Anti – Anti Sigma Factors, development progress. A comprehensive database on of internet computing engines and these two areas will be available at the knowledgebase for the analysis of protein end of these projects. A new consortium sequences and structures, development of project on Mango is being initiated this new phasing tool for faster year with 10 participating institutions from macromolecular structure determination, all over India, who are working in the area Discovery, annotation, validation and of Mango.

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DBT’s e-Library Consortium (DeLCON) the bioinformatics division like BINC, studentship and traineeship, access to online DBT e-Library Consortium (DeLCON) lecture portals and their links, launched in January 2009 is running announcements of the national successfully. More than 30 institutes are part bioinformatics coordinators meetings and its of the consortium. The institution as part of proceedings, bioinformatics publications the DeLCON are able to access more than from India and the bioinformatics resources 900 important journals. This has expedited like software and databases. Website has the pace of research in the country and been reengineered and was launched on 3rd supported for the access of scientific February 2012 during the XXIII BTISnet literature at the click of a mouse. The Coordinators Meeting at SMVDU, Katra, steering committee of the consortium meets Jammu. at regular intervals and reviews the progress of the use of various journals and to assess Coordinator’s Meeting of Biotechnology for addition or deletion of the journals from Information System Network (BTISnet) the list of subscribed journals. The portal of held at Jammu on 2nd to 4th February, the consortium can be accessed through 2012. www.delcon.gov.in. BTISnet is one of the largest network BTISnet website comprising 168 Centres including Centre of Excellence (CoE), Distributed A lot of information is required to be Information Centre (DIC), Sub-Distributed disseminated to the bioinformatics Centre Information Centre (Sub-DIC) and of the BTISnet. The BTISnet website with Bioinformatics Infrastructure Facility (BIFs). URL http://www.btisnet.gov.in provides a The progress of these Centres was central resource to all the bioinformatics continuously reviewed annually and in this centres in respect of the work done by each series the 23rd Coordinator’s Meeting was one of them in the area of bioinformatics. organised at Shri Mata Vaishno Devi Through this site, the BTIC provides all University (SMVDU), Katra on 3rd - 4th information such as budget release status February, 2012. Prior to this meeting a of submission of accounts and progress National Symposium on “Bioinformatics: report by the BTISnet Centres. The site Challenges in the post –genomic era” was provides a list of open access journals, organized on 2nd February, 2012 at details of the fellowships provided through University of Jammu.

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Fourth North Eastern Bioinformatics BTISnet are regularly organizing short term Network (NEBInet) Coordinator’s training programmes in new and upcoming Meeting areas of bioinformatics to train the researchers and scientists in the latest Under the Special drive to strengthen the developments in the fast developing area North Eastern States of the Country, a of Bioinformatics for the innovations in Bioinformatics network was established as Biology and Biotechnology and to explore “NEBInet” comprising of Centers at various the hitherto unexplored domains. Training Colleges, Universities and Research calendar of these trainings for the year 2011- Institutions under the Biotechnology 2012 was published (Figure 7.3). A total of Information System Network (BTISnet) 107 training programs have been covered programme of DBT. This Network is with connectivity of 27 Centres in all the 8 States of NE region including Sikkim to promote teaching, research and innovation through Biotechnology and Bioinformatics (BTBI) programme. During this year the Sub- Distributed Information Centre (Sub-DIC) at NEHU, Shillong was upgraded to Distributed Information Centre (DIC). The network Centres are being reviewed every year through the Coordinators Meeting of NEBInet. In this series, the 4th NEBInet Coordinator’s Meeting was held at North Eastern Regional Institute of Science and Technology (NERIST), Nirjuli, Arunachal Pradesh on 10th -11th November 2011.

Bioinformatics Training Calender 2011-2012

Short term Trainings have become an integral part of the BTISnet over last decade. Fig. 7.3: Training calendar of these trainings for the Constituent bioinformatics centres of the year 2011-2012

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in this publication in nine different areas of bioinformatics training and teachers bioinformatics. These specialized areas trainings in bioinformatics. Scientists are include Knowledge Discovery from Data, taking benefit from these trainings to make computational and structural bioinformatics, valuable contributions to their areas of network pathways and systems biology, research. The calendar has been distributed Genome and Proteome Analysis, to the Bioinformatics centres and institutions bioinformatics with respect to medical countrywide. The training calendar is also sciences, agricultural and plant sciences, available through the website of DBT http:/ environment and biodiversity, general /www.btisnet.gov.in.

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Chapter 8

BIOTECHNOLOGY PARKS AND INCUBATORS

Department established biotech parks to distillation, plant tissue culture and bio- facilitate product advancement and fertilizers. The Park is a model of active innovation through the development of collaboration between industries, research biotechnology industrial cluster and to institutions and academia and has motivated produce biotechnologists and entrepreneurs local scientists and entrepreneurs to venture having strong foundation in research and into Biotechnology and focuses on Agri-and innovation. With large number of Pharma-biotechnology and issues related to multinational and bio-pharma companies technology development. It has Quality initiating their R&D and manufacturing Management System Certificate from Norsk operations in India, the demand of biotech Akkreditering of Norway. NS-EN ISO incubators has increased. Both Central and 9001:2008/ISO 9001:2008. The Park State Governments are making efforts to significantly contributed in making Uttar promote biotechnology activities in the Pradesh a successful tissue culture hub for country by setting up biotechnology parks, banana by bringing down the cost of plants incubators as well as pilot projects through by 33% and providing good quality plants. public private partnership. DBT has Large number of farmers in the state are supported the following biotechnology growing G-9 tissue culture banana. The parks and incubation centers located in Tissue Culture facility of the Biotech Park different states. has been recognized under National Certification System of Tissue Culture raised Biotechnology Parks and Plants (NCS- TCP) by the accreditation panel Incubation Centres of DBT. During the financial year Biotech Park supplied (approx) 6.00 lacs tissue Biotechnology Park, Lucknow culture raised G-naine variety banana plants produced in tissue culture laboratory to the Biotech Park, Lucknow is fully operational cultivators under State/ National for upcoming entrepreneurs to set up their Horticulture Mission Programmes. The state R&D units in Park by providing incubator Government of Uttar Pradesh has notified facilities for solvent extraction, aqueous the Biotech Park as nodal agency along with

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the other agencies for supply of the total of 520 graduates and postgraduates biofertilizer products in the state and Ph.D. scholars received short term & government departments. long term training in different areas of biotechnology. The Biotech Park’s incubator II building has become functional and space has been leased out to setup their R&D laboratories. Besides the wet lab laboratory space, the incubator II has multipurpose meeting rooms/conference hall to accommodate 300-325 persons, offices and other related facilities.

Biotechnology Park, Bangalore (Karnataka)

DBT supported for establishing an Fig.8.1: Tissue Culture Facility setup at Biotech Park, Lucknow incubation centre and Common Instrumentation Facility at Biotechnology The park has made substantial contributions Park at Bangalore. The cost of the project to the National Mission on Biofuels by was Rs.32.26 crores and the DBT’s share developing four high yielding and oil rich was Rs.14.45 crores, out of which Rs.11.13 varieties of Jatropha curcas and providing crores has been released so far. Karnataka technical know-how for development of Biotechnology & Information Technology good nurseries and quality planting material Services, the implementing agency for the and is providing consultation to the development of the park is in process of companies in the field of bio-fuel and developing the Incubation Centre. necessary technical guidance, planting material and monitoring of the plants. BTPL Biotechnology Park, Kerala has supplied approximately 40 lacs Jatropha plants in the state of U.P. for plantation. The proposal for setting up of a Biotechnology Incubator at Kerala An important contribution of the Park has Biotechnology Park was sanctioned in March been towards building capacities of the 2005 at a total cost of Rs.23.18 crore. The much needed human resource development. share of DBT is Rs.11.00 crore and the rest The park houses 18 biotech companies. A is to be contributed by the State

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Government. An amount of Rs.2.5 crore Guwahati Biotech Park Technology has been released so far by the DBT. The Incubation Centre (GBPIC) rest amount is being released by the Department during the current financial The project of setting up of Guwahati year. The civil works of the Biotechnology Biotech Park Technology Incubation Centre Incubation Centre have been completed by has been sanctioned by the DBT at a total the state government at a cost of Rs.5.60 cost of Rs. 27.99 crore for a period of three years. An amount of Rs. 24.379 crore has crore. Various utilities have been created been released. Renovation work undertaken in the building, which has a built up area to set up the interim incubation centre for of 50,000 sq ft with 10 modular laboratory the building provided by IIT, Guwahati. The spaces of approx 1000 sq ft each and the progress of the park is regularly monitored office spaces. Besides, there is a provision by GBPIC Management Committee and for setting up of a Central Instrumentation Technical Advisory Committee. Land for Facility, Medicinal Plant Extraction Facility, setting up of the Park for constructing of Micro Propagation Facility and the permanent campus for Incubation Centre Fermentation Facility. has been identified.

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Chapter 9

INTERNATIONAL COLLABORATION

International Cooperation is an instrument lab in UW. Department in partnership with to address global challenges of food, health, ABLE have successfully conducted nutrition and climate change. Programmes Biotechnology Entrepreneurship Student pursued aim at bridging technology gap, Teams (BEST) programme for development exchange training of scientific manpower of enterprise amongst young doctoral and and leads way for the development of cost training them in techno-managerial issues. effective innovative technologies. DBT has The Department has established successful entered into bi/multi-lateral strategic collaborations with strategic partners like alliance with a focus on global challenges. Australia, Canada, Denmark, Finland, Japan, Vision behind these alliances is to promote Norway, Sweden, Switzerland, UK, EU and scientific excellence & capacity building, USA; with increasing financial commitment triggering of innovation environment from the collaborating countries for these amongst industry and academia alike. In collaborations. current year (2011-2012), six joint calls for proposals with Canada (ISTP), Denmark, Indo-Canada Finland, EU, New INDIGO and US were announced. The calls primarily focused on A joint call for proposal has been fostering closer ties through bilateral announced by DBT and ISTP, Canada in all industry-academia relationships. areas of biotechnology including Life Department in its pursuit for innovation, Sciences and medical devices. Significant capacity building and enterprise achievements of some of the ongoing development has successful ongoing projects are detailed below: programmes. These include the DBT- Wellcome Trust (WT) fellowship programme • SoftTeam, India in collaboration with on biomedical research at post-doctoral AUG, Ontario and clinical partners level; the Khorana Scholars Program with SickKids, CMC and KMH, have University of Wisconsin (UW) for Indian successfully developed software students pursuing B.Tech, M. Tech or M.Sc components which automatically degrees to spend 10-12 weeks in research acquire, store, process images from PET

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/ MRI modalities and automatically glycolide). The thermo stable detect brain tumour using these images. formulation with optimal size, highest Software can build atlas of brain encapsulation efficiency is being anatomy - registration and fusion of considered for commercialization. healthy MRI data sets and fusion of detection results from PET-MR images. Indo-Denmark

• At SJRI in collaboration with University DBT and the Danish Council for Strategic of Toronto, the system requirements for Research, Ministry of Science & Technology the platform that can function on lap and Innovation, Denmark are supporting top, store data of the blood samples from proposal in the broad area of life science: patients in remote areas and transmit it to laboratories, have been developed • This year a project on Genetics and e.g. Pilot studies have been carried out Systems Biology of Childhood Obesity successfully from remote location Barshi in India and Denmark (BIOCHILD) has (Maharashtra) having a limited been supported. connectivity and transmitted to a laboratory in Mumbai, where it was • In the ongoing project implemented at received and stored. Software is now IIT Kharagpur and IARI along with being developed for multi-lingual Technical University of Denmark, questionnaire, tracking of user timings promising strains of cyanobacteria have etc. been identified for production of biochemicals, pigments, phenolics, • In another project partnering ICGEB, biohydrogen production and increased BITS, LifeCare Innovations and nitrogen fixation ability for use as University Health Network, Toronto, 15 biofertilizer for rice, wheat cropping anti-malarial analogues have been systems in India. In addition, IIT, synthesized, characterized and screened Kharagpur is developing technology for for falcipain-2 inhibition assay. The lead increased algal biomass production. compound supplied by University Health Network, Toronto, Canada called • Under another ongoing project at KP15 has been developed as nano- SGPGIMS Lucknow, along with formulation using an US-FDA approved University of Southern Denmark, the synthetic polymer PLG (Poly-lactide-co- group has established the Small Animal

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Imaging Facility (SAIF) with installation dung) and enriched with of NanoSPECT-CT. The goal of this arbuscularmycorrhizal fungi (AMF) and facility is to provide state-of-the-art small 6 other microbes has been developed. animal imaging services to Researchers/ In greenhouse experiments this Scientists of SGPGIMS and other formulation was found to be growth Institutes of the country and to evolve promontory in tomato and lentil plants this facility into a National Training and could also control biotic and abiotic Centre. This new imaging technique has stress. been used for quantifying variable left • ventricular remodelling after stem cell In another project at UDSC, Delhi and therapy in two rat models of cardiac University of Helsinki, Finland heat disease viz. ischemia/reperfusion (I/R) shock factors (Hsfs) that bind with heat and global heart failure models. shock elements (HSEs), eventually resulting in transcriptional activation of heat shock (HS) genes have been Indo-Finland identified. Transgenic Rice plants overexpressing Hsf genes have shown Department of Biotechnology has a strong promising results in mitigating abiotic ongoing collaboration with Finland through stresses. two of Finland’s funding agencies – Academy of Finland (AoF) and TEKES. The • In the project at NEERI, Nagpur in AoF is the major Government funding collaboration with Finnish Environmental agency for basic research while TEKES is Institute, Helsinki herbicide Atrazine the funding agency for technology mineralizing isolates of microbes have innovation and industry collaboration. been identified using genomic tools from sugarcane fields. These isolates can be Three proposals under the area of food utilized as a consortium for biotechnology are being funded under the bioaugmentation and bioremediation. DBT-AoF cooperation. The trzN gene identified using genomic tools can be used for monitoring • In a project at TERI, Delhi, GBPUAT degradation of Atrazine. A DBT Pantnagar and MTT Agrifood Finland, sponsored Indo-Finland workshop on Rhizocompost from agriculture ‘Genomic tools in Bioremediation’, Nov byproducts (made from de-oiled 29-30, 2011 was successfully organised Jatropha seed cake, Rice straw and Cow at NEERI, Nagpur under the project.

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• In a project jointly executed by Indian and life history characteristics, as well Institute of Science, Bangalore and as of the breeding biology of Indirana University of Oulu, Finland successful species of Western ghats have been structure of a protein annotated as an prepared. SCP2 thiolase (STLP1) coded by Mycobacterium smegmatis was determined • Another project being carried out at at 2.7Å resolution. Protein belongs to ICGEB and VTT Technical Research Thiolases family of enzymes that Centre of Finland aimed at development catalyze the Claisen condensation of of safe recombinant forms of allergens acyl-CoA molecules in the synthetic and antibodies in plants for diagnostic direction and the thiolytic cleavage of 3- and therapeutic purposes for Allergen ketoacyl-CoA molecules in the Asp f1 (Aspergillus fumigatus) and â- degradative direction. The protein lactoglobulin (BLG) specific IgE residues known to be essential for antibodies (D1). Stably expressing catalysis in thiolases were not found transgenic tobacco and barley cell to be conserved suggesting that STLP1 cultures, tobacco plants and barley seeds has another, yet to be discovered for D1 antibodies have been obtained function. and a procedure for purifying antibodies from tobacco leaf extracts has been • The group at Rajiv Gandhi Centre for developed. Biotechnology, Kerala in collaboration with University of Helsinki has • Project being implemented at IISER, identified the presence of deadly Pune and at Turku Centre for pathogen, Batrachochytrium dendrobatidis Biotechnology, Finland envisages amongst Indirana frogs from the Western establishing patterns in the levels of Ghats. The pathogen is responsible for serum proteins that would be descriptive the world wide depletion of amphibians of increased risk, progression and early and is reported in Indian frogs for the onset of T1-Diabeties from patients at first time. In addition they have various stages of T1D development. The documented high cryptic diversity of important goal is to help understand endemic Indirana frogs in the Western the development of T1D, and find novel Ghats. A comprehensive review of combinations and biomarkers. Towards taxonomy (including all known this end candidate proteins have been synonyms), systematics, morphological identified in the serum.

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fumigatus caused allergy and Indo-Germany desensitization therapies of allergic disorder. Based on immunoproteomic Under the cooperation in biotechnology approach twenty new allergenic proteins between Department of Biotechnology of A. fumigatus have been identified. The (DBT), Government of India and German panel of newly identified allergens will Federal Ministry of Education, Science be useful in designing peptides of Research and Technology (BMBF) diagnostic and therapeutic value. forschungzentrum Julich GMBH (FZJ) a 2+2 programme has been initiated, in which joint • The ongoing project at NCL Pune and projects would be developed with at University Anhalt, Germany has been participation of one research institute and successful in integrated carbon recovery one industry from each side. Nine projects using photo-bioreactor grown algal are underway and the major outcomes are biomass to enrich methane from biogas given below: using polypropylene hollow fiber membranes as contactors, for recovering more than 90% of the CO from biogas • Project being implemented at ICAR, Goa 2 using sewage as a sweep liquid in a and Justus-Leibig University, Germany two stage membrane process. A has resulted in development of an ELISA provisional patent has been filed for the based assay using listeriolysin O as an technology. antigen, which is being commercialised for Listeria monocytogenes detection. A • Under the project being implemented at protocol for real time PCR assay of the GBPUAT, Pantnagar and University of pathogen has also been developed. A Munster, Germany, 20 highly copper significant achievement of the project is tolerant isolates of fungal antagonist the establishment of well characterized Trichoderma were collected from different repository of the strains of Listeria agro-climatic conditions. Field evaluation isolated from almost 12 states of India. of different copper based fungicide compounds and Trichoderma against • Ongoing project at IGIB Delhi and at potato have been successfully Abteilung Klinische Chemie- conducted. Zentrallabor, Gottingen, Germany aims to develop methodologies for specific • In a project jointly executed by IISc., and early diagnosis of Aspergillus Bangalore and Deutsches Krebsfor-

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schungszentrum Germany, serum microsatellite and 98 novel intron length samples from GBMs and healthy polymorphic markers were developed controls were analysed for 810 cancer for eventual use in diversity analysis specific markers by antibody and breeding programmes. microarrays. It was concluded that CRP has potential to serve as an independent • The ongoing project being carried out prognostic marker for GBM. at ICGEB, Delhi and Helmholtz Centre for Infection Research Germany is based • Ongoing project at NIRRH, Mumbai and on the evidence that the dengue virus Max Planck Instt. for Molecular envelope domain III (EDIII) is a potential BioMedicine Germany, functional vaccine antigen. Successful secretory validation of Oct-4 gene presumed to expression, purification and have role in the process of self-renewal characterization of monovalent dengue of spermatogonial stem cells was EDIII antigens corresponding to four validated by knock down of endogenous serotypes of dengue virus has been expression of SSC utilizing lentiviral achieved. Immunogenicity studies mediated shRNA approach. Currently; demonstrate that all the EDIII recognize studies are underway to evaluate the anti-EDIII antibodies in a serotype effect of Oct-4 knock-down on the specific manner. expression of genes involved in SSC self- renewal whose functions are under the • Ongoing project running at SGPGIMS, control of Oct-4. Lucknow and Institute of Neuroscience • In the ongoing project at NIPGR, Delhi and Medicine, Germany successfully and Leibniz Instt. of Plant Genetics and correlates the role of Vitamin B-12 in Crop Plant Research Germany, it was brain development using modern concluded that the tolerant cultivars of imaging techniques revealed reduction foxtail millet possess wider array of in the anterior thalamic radiation (ATR) antioxidant machinery with efficient & posterior thalamic radiation (PTR) ascorbate-glutathione pathway to cope fibers bundles of patient with vitamin with drought-induced oxidative stress. b12 deficiency as compared to controls. A synonymous single nucleotide Project was successful in correlating polymorphism (SNP) associated with development of different regions of dehydration tolerance was detected in brain in relation to cognitive ability of the SiDREB2. A set of 147 genomic individuals with vitamin B12 deficiency.

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• Under the project at ILS Bhubaneswar • The ongoing project at CCMB, and Inst. of Medical Microbiology, Hyderabad and Max-Planck- Institute for Immunology and Parasitology (IMMIP), Infection-Biology Germany have University Clinic at Bonn, Germany a successfully validated the hypothesis deletion of 23 bp was identified in Toll that the small GTPase Rap1A, plays an like receptor 2 in patients suffering important role in macrophage adhesion from Bancroftian filariasis. Toll like process and phagocytosis of Mtb, hence receptor 2 plays an important role in in tuberculosis disease establishment human filariasis by recognizing and progression. Wolbachia, an endosymbiont of filarial parasite and induce inflammatory • In the collaborative project between immune responses. GNDU, Amritsar and Humboldt University Germany genes responsible • The group at University of Mysore and for different type of retinal dystrophy University Hospital of Freiburg has been successfully identified by Germany has successfully found that whole genome linkage analysis in an angiogenic receptors Flt-1 and Tie-2 are autosomal dominant retinitis pigmentosa overexpressed in human breast cancer the disease linked locus has been cell lines and in human biopsies from identified and a novel 7bp deletion has breast cancer patients. Project will pave been identified in candidate gene way for treatment of breast cancer using PRPF31 at the mapped region. A immunoliposomes. previously unreported mutation has also been identified in CNGA1 gene. • In another ongoing project at University of Delhi, South Campus, and University • In the ongoing project at CCMB, of Heidelberg Germany two (nPAC35 Hyderabad and Brenneckestr, and 75) novel photoactivated adenylate Magdeburg, Germany the molecular cyclases (PACs) were cloned, purified basis of biogenesis of calneurons has and characterized for the photo-dynamic been described. Calneurons are EF-hand kinetic properties. For the first neuronal calcium sensors that are time, bacterial light-gated ion pumping localized at the trans-golgi network rhodopsin (CvRh) was localized (TGN) where they regulate vesicle in plasma membrane of eukaryotic trafficking from TGN to plasma algae. membrane.

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and acceptance of spacing methods Indo-Sweden through a gender-equity focused family planning intervention delivered by the • The major focus of the proposal at IISc, village health care providers. Bangalore and at Uppsala University, Sweden has been to establish and • Under the ongoing project at ICMR Delhi characterize an in vivo assay system for and Boston University, Schol of Public initiation of protein synthesis in Health USA, the preparatory activities Mycobacterium smegmatis. The assay for one year have been completed which system has been established however, includes procurement of all regulatory to establish which amino acid is used to approvals of ICMR (TEP, DCGI initiate protein synthesis various mutants clearance, Institute Ethics clearance) and of the initiator tRNA for its structure- finalization of working proposal, Case function analysis has been generated. Record Forms, Instruction manual, Standard operating guidelines, CSpro • In another project at IISc., Bangalore and database, certification training in GCP at Translational Immunology at SMI, and Ethics and Investigators’ meeting for Sweden, it was found that expression of initiation of the study and training in Rv3852, a topology modulator protein the conduct of the study. Pre and post- from M tuberculosis resulted in alteration training of Health care Providers’ (HCP) of nucleoid morphology. Structure of was also done. M.tuberculosis HU protein was also determined and molecules are now Stanford-India Biodesign Programme - being designed to inhibit its activity. A Novel Collaborative Technology Innovation Indo-US Stanford-India Biodesign (SIB) programme A joint call for proposal was issued and is a innovation programme to create medical seven proposals were received: technology innovators in India by involving IITs, leading engineering institutions and • At NIIRH Mumbai and Boston partner medical institutions. In India, this University, USA the currently ongoing programme is centered at AIIMS, and IIT, intervention study is to enhance rural Delhi. The objective of this programme is young couple’s contraceptive knowledge to train next generation of medical

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technology innovators who will in turn focus Four Annual Medtech Summits have been on invention and early stage development organised so far with the aim to bring of low cost new medical technologies for together the thought leaders of the emerging the Indian population. The key steps in the medical technology industry in India. The biodesign process are: identify fellows objectives of these summits were to through national competition, create a team understand the current state of the industry, and train them in innovation process, to identify issues facing it and to delineate identify needs, define prototype profile, key activities that will help chart its future relevance, initial product development, course. preclinical validation, large scale clinical validation and commercialization. A model of innovation has been created which has resulted in filing of 10 patents So far, 16 fellows have been trained at (international & national). This includes: i) Stanford University, USA in clinical four complete specifications on: a) immersion process in four batches. These Apparatus for vascular access in emergency fellows have trained 21 interns in India. Fifth situation; b) An immobilization device; c) batch has joined Stanford University for Device for collecting fecal discharge in training in biodesign process in January 2012 incontinent patients; d) Transfer sheet; ii) for a period of five months. The fellows of four PCT applications on: a) Device for the first batch have established a start-up vascular access; b) A medical device for company and are developing the fecal limb immobilization; c) Device for collecting incontinence device. The fellows of other fecal discharge in incontinent patients; and batches are developing devices such as d) Transfer sheet; iii) two provisional patents intraosseous device, limb immobilization on: a) A device and a method for auditory device, patient transfer life, mucus screening; and b) Device for mucus removal dislodging device, etc. Initial prototypes are and dislodging. also being developed for: i) a better way to conduct neonatal hearing screening in Phase-II of SIB Programme resource constrained settings; ii) a better way to conduct screening for retinopathy for Phase-II of this programme has been prematurity in neonates; and iii) a better initiated that includes selection/filtration of way to provide resuscitation in order to clinical needs, development of prototypes, manage birth asphyxia in a resource validation, animal studies, technology constrained setting. transfer and commercialization. Inter-

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Institutional Agreement was revised and Programme for Scholars named in honor of executed between Stanford University, Har Gobind Khorana. The Khorana Stanford-India Biodesign Centre at AIIMS & Programme provides an opportunity to IIT-Delhi and DBT. The Fellowship Indian scientists (currently enrolled in Agreement was formulated and executed B.Tech., M.Tech. and M.Sc. programs in with the fellows and interns of 2010 batch. Biotechnology and allied areas) to undertake Collaboration has been promoted between research internships at UW. DBT provides the fellows and industries. a fellowship grant of US$ 2,000 for a period of 10-12 weeks. Fifteen candidates were Technology Transfer and commercialization selected for the award of the scholarship.

A Technology Transfer Committee has been The programme has been extended for constituted by the Department to deal with another period of three years. Department the issues being faced by the Fellows in has also initiated Technology Transfer negotiation with the companies for Course for Indian Science professionals at technology transfer and commercialization. University of Wisconsin. This program will This Committee has negotiated with the benefit DBT, which is in the process of industries for transfer of technologies setting up a number of institutes for developed at various stages. A number of innovation and translational research as prime mandate. formats and agreements have been developed and finalized. The Department has engaged Biotech Consortium India Ltd. Indo-UK as a management organization of the this programme. The support services for this Bioenergy has been identified as a scientific programme are also being provided by the area that receives significant funding from BBSRC in the UK and DBT in India; both Biotechnology Industry Research and countries currently invest in second Development Assistant Programme (BIRAP). generation and beyond bioenergy and biofuels. Under this cooperation, a joint Khorana Programme for Scholars Indo-UK workshop held in New Delhi in October, 2011 by DBT and BBSRC. As a Department of Biotechnology, University of follow-up, a joint call for sustainable Wisconsin-Madison and IUSSTF have bioenergy research between India and UK partnered to support prestigious Khorana will be announced. A total of £ 10 million

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would be committed by DBT and BBSRC from both DBT and WT for running the towards this call. The collaborative fellowship. programme on bioenergy envisaged in this workshop aims to solve shared problems The Wellcome Trust/DBT India Alliance in the production and processing of plants runs three fellowship schemes: Early Career (mostly waste) and algae for bioenergy. (for newly qualified Ph.Ds), Intermediate Another joint DBT-BBSRC workshop on (for those with 4 – 7 years post-Ph.D research “Livestock health and diseases” was held experience) and Senior (for those with 7 – in February 2012 in Delhi. 12 years post-Ph.D research experience). So far, 50 fellowships have been awarded - 11 The University of Edinburgh (UofE) has under Senior Fellowship; 26 under been actively pursuing collaboration with Intermediate and 13 under Early Career India in the area of biological sciences. A fellowships. This year onward a new Letter of Intent (LoI) was signed in January fellowship – The “Margdarshi Fellowship” has 2012 during the visit of Professor Sir been initiated for scientific leaders who Timothy O’Shea, Vice Chancellor, University already lead research laboratory and wish of Edinburgh. to relocate from their current institution within India or overseas. Wellcome Trust-DBT India Alliance Indo-EU The Department of Biotechnology under the Ministry of Science and Technology has An India-EU synchronized joint call on partnered with Wellcome Trust (WT) to biotechnological waste water treatment and launch a three-tier fellowship programme reuse in agronomical systems with • 6 on biomedical research at post-doctoral Million from EC side was announced. Five level. The Department of Biotechnology proposals were received. and the Wellcome Trust have committed Pounds Sterling 8 million each year, for a • Under the ongoing project NAMASTE period of five years. The programme is at North East Institute of Science and being delivered by a Special Purpose Technology partnering with EIRC, UAS Vehicle (SPV), a public charitable trust Bangalore including partners from Italy, registered as The Wellcome Trust/DBT UK, Spain, Hungary and Netherlands, India Alliance with the office situated at development of pretreatment Hyderabad. The Trust receives contribution technologies for stabilization and

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preservation of byproducts of food Karolinska Instt., IC50 values of Gentinella industry and subsequent recovery of lutea extracts (water and methanol useful products under project protocols extract), astaxanthin and pro- for stabilization and preservation of rice anthocyanidine B2 on primary cultures bran, pomegranate and mango peel of rat aortic smooth muscle cells and on waste have been developed. Production smooth muscle cell lines (A7r5 and of Lactic acid using unsterilized defatted HASMC) have been determined. Among rice bran by simultaneous the compounds tested for anti- saccharification and Fermentation are in atherogenic property, ellagic acid and progress. Enzymatic method for recovery water extract of Gentinella blocked PDGF- of insoluble dietary fibre for probiotic induced smooth muscle cells preparation from rice bran on laboratory proliferation. They also blocked PDGF- scale has been developed. Isolation of induced production of nitric oxide (NO) dietary fiber from mango and and reactive oxygen species (ROS) in pomegranate peel powder is under smooth muscle cells. Process of progress. Laboratory scale extraction elucidating the signaling mechanisms protocol for pectin from pomegranate involved in imparting athero-protective and mango peel has been completed. effects of these compounds is under Protocol was developed for extraction progress. of total phenolics and natural colour (Anthocyanins) from rice bran. ERA-NET Optimization work for Ferulic acid extraction is in progress. Completed Department of Biotechnology is part of the extraction of poly phenols from both new INDIGO project which is the first pomegranate and mango peel. Protein European Research Area Network concentrate from defatted rice bran was Programme (ERA-Net) in India. extracted by using both alkaline and enzymatic method. A call for proposals has been announced in the area of biotechnology applied to human • In another ongoing project being health. Some of the achievements under the implemented at Annamalai University ongoing project are as follows: alongwith NIN Hyderabad and IIT Madras, with partners from Stockholm • Under the project (ANTICHIK) being Univ., Italy, Germany, Serbia and implemented at University of Madras,

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BITS, Mesra and Luebeck University, Spain studies conducted in the insulin Germany , CHIKV nsp3 macrodomain resistant rats (High fat fed rats), a has been characterized. The ADP-ribose representative model of insulin is a well conserved protein bound resistance, have demonstrated enhanced ligand for the CHIKV nSP3 free radical generation from neutrophils macrodomain. This is an attractive target as well as significant increase in the for this virus and virtual screening for myocardial injury following coronary drug molecules, which can bind at this artery ligation. site and may produce some inhibitory action against chickangunya virus. • Under the program PLANTY at National Chemical Laboratory, Pune involving 5 • For the execution of project running at European partners (Austria, Spain, AIIMS Delhi and Universitats klinikum Netherlands, Turkey and Germany), a Jena, Germany a workshop was modest experimental program on value conducted in Jena, Germany in addition to the pomegranate fruit was November. initiated. 50 kg batches of the variety Bhagwa were processed for recovery of • The project at Indian Institute of various components of the fruit (arils, Technology, Madras (consisting of peel and pomace). Detailed analysis of partners from Germany, Turkey and each of these components were Austria) aims at developing an early performed and a material balance for warning system for failure of bileaflet processing of pomegranate was arrived mechanical heart valves by developing a upon for subsequent scaling up. Peel magnetic sensor. Titanium bileaflets have was found to be a rich source of anti- been designed and fabricated. Diamond oxidants and animal feed trials are Like Carbon (DLC) and a magnetic proposed using this material as an coating (Ni:Fe) have been deposited ingredient. Similarly, the seed found in onto the titanium leaflets. The the pomace was found to be a rich source haemolysis for these coatings have been (46% w/w) of poly-unsaturated fatty studied. Results are positive and acids (PUFA’s). The fruit juice was encouraging. clarified using membranes and was found to be a very pleasant drink • In another project being undertaken at suitable for packaging. Further studies Central Drug Research Institute are planned on encapsulation of the anti- Lucknow and Institute de Biologia, oxidants from peel and the seed oil.

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• Ongoing project at Central Potato • Four kinds of magnesium based Research Institute, Shimla involving biodegradable alloys have been tested partners from Netherlands, Spain, at CCMB, Hyderabad, as implants in Germany and UK, expression of the FT bone injury models created in rabbits analog StSP6A this gene was and found that the MgZrSr2 alloy is investigated in three Indian potato found to be the most efficient. cultivars, viz. Kufri Giriraj (Long Day), Kufri Arun (Short Day) and Kufri Jyoti • To improve management of diabetic (Day Neutral). A correlation was ulcers, 510 wound samples from diabetic observed between StSP6A expression ulcer patients have been collected and and tuber initiation in case of day-neutral microbes isolated and identified at and long-day cultivars. Similarly, Manipal Life Sciences Centre (MLSC), expression of this gene was investigated Manipal. Antimicrobial profile and in Kufri Chandramukhi (heat sensitive biofilm producing capability of these cultivar) and Kufri Surya (heat tolerant microbes are under study to identify cultivar). Expression of StSp6A was suitable biomarkers for rapid diagnosis. inhibited at 240C in heat-sensitive cultivar Kufri Chandramukhi, while in • The Veterinary College, KVAFS heat tolerant cultivar Kufri Surya University, Bangalore and Ella induction of this gene was observed Foundation, Hyderabad have jointly even at higher temperature. Expression developed a PCR for identification and of this gene was induced during capsular typing of Staphylococcus aureus tuberization at 180C in both the cultivars. as a part of development of an effective vaccine for the prevention of Indo-Australia staphylococcal mastitis in bovines.

A joint call for proposal under the sixth • In order to develop a high salinity and round was announced this year and drought tolerant rice (in India) and proposals were invited in the areas of Stem wheat (in Australia) varieties gene Cells; Vaccines/ Medical Diagnostics; constructs (Gly I, Gly II, and PDH45 Transgenic Crops and Marker-assisted genes) have been prepared at ICGEB and Breeding; and Bioenergy & Biofuels. transferred to Australian collaborators. Highlights of some of the projects supported The rice plants have been grown under under this collaboration are given below: stress conditions for further study.

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Wheat transformation has already been heterogeneous genetically. A genome- set up by Australian collaborators with wide approach has lead to the these constructs. identification of two important genes, namely KLHL26 and TSHZ2 may carry • At IARI, Delhi, transcriptome sequencing mutations that cause PCG in the Indian of wheat cyst nematode, Heterodera avenae population. an important pest of wheat has been initiated. This is first report of illumina Indo-Norway sequencing platform used for transcriptome sequencing of plant A Multicentric Indo-Norwegian programme parasitic nematodes. on vaccine platform in the area of aquaculture was continued this year. • Various sorghum varieties from India by ICT, Mumbai and Australia were • Work on Development and evaluation screened for extraction of kafirin. Kafirin, of bacterial (Aeromonas hydrophila and a prolamin protein was successfully Edwardsiella tarda) vaccines for finfish extracted from sorghum and based on outer membrane proteins characterized by various analytical (OMP) was initiated at College of techniques. Fisheries Mangalore. Aeromonas hydrophila and Edwardsiella tarda is • In the project at ICT Mumbai, a Novel responsible for serious economic losses process for extraction of kafirin from for fish-farming industry due to serious sorghum seeds and Kafirin based disease manifestation. Recombinant nanoparticles as novel drug delivery vaccines were developed against these system (NDDS) have been developed. pathogens. These vaccines were tested Preliminary studies have shown better for immunogenicity in fishes. The study anticancer effect of this formulation than indicates the potential of the OMPs for that of standard drug. protecting carp and rohu through vaccination. • Variations in the CYP1B1 gene have been found to cause autosomal recessive • In another programme, work on Primary Congenital Glaucoma (PCG) in immunomodulation studies in several world populations. However, in freshwater prawn Macrobrachium India PCG appears to be highly rosenbergii using three recombinant

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proteins of Macrobrachium rosenbergii nodavirus was carried out with the THSTI-IAVI HIV Vaccine collaborative efforts of CIFA and CIBA. Research Programme Based on the sequence analysis of three MrNV genes (Capsid, RdRp, B2), the THSTI and IAVI have agreed to set up a tertiary structure was predicted. The collaborative effort towards advancement of innovation, facilitate collaboration, build MrNV RdRp and capsid protein were centres of excellence and invest in next able to reduce the viral load indicating generation of scientists and to accelerate the that these proteins may act as HIV Vaccine discovery program. The key immunomodulatora against white tail components would be designing, testing and disease (WTD) in Macrobrachium implementing high-throughput strategies for rosenbergii. HIV-1 envelope-based immunogen screening and prioritization to help DBT-IAVI Collaboration discovery and advancement of novel HIV vaccine candidates. The program is targeted The collaborative programme has been to expand the number of vaccine candidates further extended for another period of 5 globally for testing, and enhance the speed years w.e.f 7th July, 2010. Under the aegis with which they can be assayed. The of Indian Medicinal Chemistry Programme, unique industrial-type high-throughput 2 projects have been funded and the vaccine design, screening and selection funding will continue for next phase. The processes proposed for the THSTI-IAVI study at ICGEB, New Delhi focuses on HIV-1 Vaccine Lab will be largely facilitated development of conformationally preferred by interdisciplinary interaction and will be peptide immunogens as candidates against driven by the principles of international HIV-infection. The emphasis is on collaboration, high-quality science and designing peptide immunogens to elicit vaccine-oriented research. HIV-1 neutralizing monoclonal antibodies. Study at IISc, Bangalore is directed towards Indo-Swiss Collaboration designing and characterization of novel Outer Domain (OD) derived immunogens The Indo-Swiss Collaboration in with additional mutations to prevent Biotechnology programme started in 1998 protein aggregation. The significant with an agreement between Department of outcomes from the studies have been Biotechnology and Swiss Agency for patented. Development and Cooperation with the

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mandate to develop products and leaf agglutinin (ASAL) gene constructs biotechnological processes, which have an under CaMV35S promoter and phloem impact on poverty alleviation and tissue specific rolC promoter were sustainable management of natural resources performed. The preliminary results of in India; to focus on innovative technologies biosafety analysis indicate that ASAL in agriculture and environmental research may be considered as apparently safe and; to build capacities and R&D molecule. partnerships between Swiss and Indian institutions and private companies with • In another project executed under the strong economic, social, and ecological pulse network at Assam Agricultural relevance. University, Jorhat, in collaboration with ICRISAT, Patancheru, India transgenic lines of chickpea carrying the chimeric Currently, the programme is in its third Bt-Cry2Aa gene to confer protection phase (2008-2011) involving 120 researchers against pod borer (Helicoverpa including private sector aiming at armigera) have been generated at AAU. technology development and advancement The transgenic seeds were transferred by validating various projects of phase-II in to ICRISAT. terms of prototype products. During the third year (2010-2011) of this phase, two • The biofertilizer network aims at main activities viz. the Technology producing plant growth promoter Advancement Unit (TAU) was established bacteria and Mycorrhizal formulation for and the South-North-South collaboration in enhancing nutrition mobilization and pulse technologies at the BARI (Bangladesh uptake in cereal and pulses. TERI has Agricultural Research Institute) was successfully developed a consortium of identified as a possible institute for Arbuscular Mycorrhizal Fungi (AMF) collaboration. and Plant Growth Promoting Rhizobacteria (PGPR) which were tested • In the Pulse Network project in an effort in multi-location field validation trials to develop Aphid resistant chick pea in low input agricultural fields for plants, being executed at Bose Institute, enhancing wheat productivity. Kolkata successful multiplication and analysis of transgene expression of • In a project executed under biofertilizer existing transgenic chickpea lines network at GB Pant University of developed with chimeric Allium sativum Agriculture and Technology (GBPUAT),

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Department of Biological Sciences, wheat cultivars with greater yield at high Pantnagar, India a combination of temperatures, it is essential to consortia AMF and two of the Plant understand the effects of high Growth Promoting Rhizobacteria (PGPR) temperature on the process of starch have been optimized for commercial accumulation. Two wheat genotypes; production. Halna (heat tolerant) and Raj 4014 (heat susceptible) were exposed to higher • Under the wheat network, projects were temperature during the grain filling. supported for fungal disease resistance Primers for genes; ADP-glucose and terminal heat tolerance in wheat. At pyrophosphorylase (large and small PAU, Ludhiana a recombinant inbred subunits), SSI and SSIII amplified the line (RIL) population derived from the desired product. cross Triticum boeoticum / T. monococcum • NCL, Pune has transferred the was developed and the genes Leaf rust mycoinsecticide technology to the resistance, stripe rust resistance, and private sector viz. HiTech Bioscience powdery mildew resistance were India Ltd. (HTBS), Pune. The mass mapped. Under another project production of Metarhizium conidia strains Directorate of Wheat Research, Karnal, using solid state fermentation (rice as has identified identify molecular markers substrate) was carried out at at NCL linked to the genes for stripe rust and the optimization for large scale resistance for accomplishing marker production of the same was done at assisted pyramiding, using three HTBS for commercial strain M34412. recombinant inbred line (RIL) Desired modifications were done by populations developed from the crosses manufacturer Wadegati Labequip Pvt. Cappelle Desprez and its substitution Ltd. line Cappelle Desprez (Mara-2D); Capelle Desprez / PBW343 and Capelle • Full-length genomes of viruses Desprez (Mara 2D) / PBW343. In a yet associated with the cassava mosaic another project, for molecular mapping disease were cloned and sequenced and identification of QTLs for heat stress from five cassava genotypes collected at tolerance, parental screening with more six locations in South India at MKU, than 375 SSRs and screening of the RIL Madurai. The RNAi constructs have been population with about 75 SSRs have transformed in tobacco to assess its role been accomplished. In order to develop in disease control in cassava.

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and structure of target molecules with Indo -Tunisia potential applications in creating the artificial proteins for engineering. The A ‘Programme of Co-operation’ (POC) signed between Republic of India and projects comprise of four challenging Republic of Tunisia in 2006 for five years themes in the area of Bioinformatics. in the area of biotechnology with an These include (1) Designing potential objective to develop and support targets in membrane proteins, (2) collaborative research activities in the area Designing GPCRs Mimetics (3) of agriculture and health care. The POC is Designing FIXER for disorders, and (4) extended recently for another five years on Designing cybrog lectins. Computational mutual agreement with a commitment to cooperate for fruitful outcomes. Biology Research Centre (CBRC), Tokyo, a constituent institute of AIST has been Indo-France engaged for these projects with six major institutions in India. A ‘Memorandum of Understanding’ (MOU) signed between India and CNRS, France is • Four projects have also been launched recently renewed with an objective to last year in cell engineering to identify establish International Associated novel drug targets and therapeutics for Laboratories (LIA) in the area of cancer. The projects involve (i) biotechnology as well as to launch a new International Masters and Ph.D. The new Understanding molecular mechanisms programmes are under discussion for controlling dual role of Ras, Sirtuins and signing the necessary agreements CARF in relation to cellular proliferation and senescence, (ii) Studying the Role Indo-Japan (s) of Mortalin and CARF networks in ovarian cancer, (iii) Studying the use of DBT, India and AIST, Japan has initiated Ashwagandha derived phytochemicals eight major projects in the area of bioinformatics and cell engineering. for development of differentiation-based therapy of brain cancers, and (iv) Insights • The bioinformatics projects which were into secondary metabolite production sanctioned in 2009-2010 utilize and their accumulation in Withania bioinformatics tools to analyze sequence somnifera using in vitro propagation

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system. The Cell Engineering Institute All these developments have been reviewed of AIST at Tsukuba is working with by the Joint Committee of Indo-Japan during th four major institutions from India for the 4 bilateral Workshop which was organized in India on 13-14 December, 2010. these projects.

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244 Chapter 10

AUTONOMOUS INSTITUTIONS

An effort in cancer biomarker discovery National Institute of Immunology shown sperm-associated antigen 9 is (NII), New Delhi involved in tumorigenicity as well as tumor growth. Effective combination treatment for NII, New Delhi continued its activities to teratocarcinoma, the cancer of the testis, by promote and conduct high-quality research a combination of cisplatin and a plant in the area of immunology and related flavonoid fisetin is providing a lead for sciences. The core areas of research include formulation of better treatments. infection and immunity, molecular design, reproduction and development and gene A number of promising leads were reported regulation. Significant achievements in these on the biology of Mycobacterium tuberculosis. areas during the year are as follows: HisB, an important protein in the histidine- biosynthetic pathway of Mycobacterium In the field of basic immunology, the major tuberculosis was crystallized and preliminary scientific findings included deciphering the X-ray crystallographic analysis reported. In role of Bruton’s tyrosine kinase, a kinase another project the mechanisms of infection implicated in primary immunodeficiency by Mycobacterium tuberculosis studies disease, in macrophage cell death. Studies suggests that the PE family of proteins are with inflammatory disorders showed that possibly related to latency, where anti-hemoglobin autoreactive antibodies Mycobacterium smegmatis was used as a model occur quite frequently in humans was due to overexpress PE proteins. to release of hemoglobin and have inflammatory consequences. Japanese encephalitis virus (JEV) showed the binding of La protein, a protein that Studies on mechanisms of cancer induction, associates with many small RNAs to the 32 discovery of biomarkers and improvement - and 52 -noncoding regions of the JEV of therapy provide key insights into the genome. Mechanisms of infection studies role of PGC-1á, a primary regulator of with HIV virus showed that human T cell energy metabolism in mediating p53 action. apoptosis occurs through p53 mediated

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pathway due to inhibition of ubiquitination through symposia, conference and public of p53 by the HIV protein Vpu. lectures to the community at large is a basic Investigations into the mechanism of mandate for NII. An International influenza virus survival showed that the Symposium on Cancer Biology was held at cleavage of the M1 gene of the virus was the Institute provided timely and critical significantly augmented when designed information on how to take an idea from antisense molecules hybridized close to the the laboratory to the clinic and consequently cleavage site. to the market place.

The c-kit, the master signalling molecule of Training programs to postgraduate students, haematopoietic stem cells helps in early short-term training for project work or recovery of the haematopoietic compartment dissertation provided. The robust Ph.D in irradiated hosts. In another study with programme registered 35 students during Hemophilia A, which is caused by mutation the year for Ph.D. degree while 27 students in factor VIII gene in humans, it has been received Ph.D. degree during 2011-2012 with shown that bone marrow derived academic affiliation of Jawaharlal Nehru hepatocytes and endothelial cells can University, New Delhi. An agreement was synthesize FVIII in liver and correct signed with the National Cancer Institute in bleeding phenotype in Hemophilia A mice. the US for undertaking clinical trials at the Sloan Kettering Memorial cancer hospital A cytochrome P450 protein identified as in New York to focus work on cervical CYP5122A1 is an important molecule linked cancer, the vaccine’s efficacy against ovarian to processes like cell growth, infection and cancer. NII has been involved in clinical ergosterol biosynthesis in the parasite trial of Rotavirus vaccine developed to Leishmania donovani thus providing a lead reduce the incidence of diarrhea or its for future drug development. Bromo- severity in neonatal children continues. NII benzothiophene carboxamide derivatives published 109 high quality research papers have been shown to be potent inhibitors of in peer-review journals. Plasmodium sexual blood-stages both in vitro and also in the mouse model. National Centre for Cell Science (NCCS), Pune Dissemination of scientific information through professional journals to the NCCS is committed to its contribution worldwide community of scholars and towards Human Resource Development, by

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way of reaching out to individuals at all The institute focuses on important questions levels including students, teachers and relevant to human health, specifically in the researchers in India. Basic training as well area of regenerative medicine, infectious as custom-made programmes depending on diseases and lifestyle induced health specific requirements of smaller groups of adversities. In stem cell therapy the researchers were conducted at NCCS and at procedures for isolation, expansion, cryo- the user’s end. In the past year, NCCS has preservation and differentiation of stem cells provided training to over 17 researchers into specific cell types have been optimized. from various organizations across the Considerable efforts are also being made to country, and 12 students have successfully understand the cellular and molecular completed PhD at NCCS. NCCS has mechanisms defining stem cell niche in supplied over 2300 cell lines to 120 normal organs (Fig. 10.1). organizations.

Fig. 10.1: 3D- Mesenchymal Stem Cells Foster primitive stem cell pool, (A) 3D-CD34+ cell population contained significantly higher percentage of cells expressing primitive HSC-markers: CD133 (upper panel) and CXCR4 (lower panel)(B)Data from three independent experiments are depicted (N=3), (C) Most 3D-CE34+ cells (Cy3) express N- Cadherin (FITC), albeit at variable levels. (D) Huge expanse of DC34+ N-cadherin+ cells under 3D-conditions. (Tile mode, pixel size 2048x2048), DAPI (blue) demarcates nuclei (blue).

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Scientist at NCCS studied immune system that nuclear matrix associated proteins like functions to evolve mechanisms leading to SATB1 and SMAR1 regulate global gene infections, identifying molecular players expression by chromatin remodelling. involved in host-pathogen interactions in Currently, we are exploring the functions of developing strategies to combat infections. these two players in immuno-modulation Towards this studied the mechanism of and tumourigenesis. viral evasion of human complement system, regulation of CD40 signaling in host cells Diabetes is a multi-factorial metabolic during Leishmaniasis, protein trafficking in disorder and the incidence of it is increasing Leishmania, HIV biology and host-pathogen at an alarming rate. NCCS focuses on interactions during Plasmodium, understanding the mechanisms involved in Mycobacterium and Candida infections. endocrine pancreas development and Hyper-activation of immune system is regulation of insulin biosynthesis. Scientists frequently observed in many inflammatory have identified the molecular mechanisms and autoimmune disorders. NCCS is regulating the insulin production and the investigating the role of the chemokines that intricate relationship between the diabetes- are involved in regulating these processes. induced cardiomyopathy and oxidative stress. Osteoporosis is another major disease Cancer is a complex disease caused by mis- that affects a large proportion of our regulation of signalling networks. In order population, which is caused by the to understand the biology of imbalance in bone formation and tumourigenesis, NCCS is exploring resorption. Researchers have shown that pathways involving critical players in immuno-modulators like IL3 play an different signalling cascades involving essential role in differentiation of osteoblasts Osteopontin, eNOS, p53, Cyclin D1, Snail, and thereby augmenting the bone Slug, mTOR, Wnt, etc. Efforts are made to regeneration. elucidate the molecular networks underlying oncogene induced senescence. The outcome The challenge in understanding biological from these studies is expected to provide processes is deciphering the underlying tools for better treatment of cancer. complex and dynamic networks. System biology approach is focused on delineating Epigenetic regulation of gene expression these networks and their interactions. plays an important role in various cellular Integrating the de novo drug design, abstract processes. Scientists at NCCS have shown fragment based drug design and

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sophisticated molecular simulations is a DNA Sequencer. The challenge for biology thrust area of research at NCCS. at present is the need to deal with the incredibly complex and enormous amount Microbial flora within an organism of data generated. To this end, a high influences the metabolic processes of the performance computing machine have been host. Using advanced molecular methods procured and installed, which provides such as whole genome sequencing and access to a scalable pool of computing meta-genomic analysis, efforts are made to resources. unravel the complex microbial ecosystem in the mid-guts of humans and insects of NCCS has published over 50 scientific clinical importance. For the conservation and papers in peer reviewed journals in the exploitation of biodiversity in India, reporting year. The scientific activity at microbial culture collection centre (MCC) NCCS is facilitated by funding from various was established in NCCS, with a special national and international agencies. mandate from DBT. The centre focuses on basic research in the areas of microbial National Brain Research Centre diversity, taxonomy, genomics and (NBRC), Manesar, Haryana proteomics, in addition to its role as a National facility for microbial culture NBRC continued its mandate and focused collection and International Depositary its research and development activities on Authority. NCCS has undertaken the efforts inter disciplinary science from molecular to identify novel biomarkers for breast biology and genetics through psychology cancer, using integrated proteomic, genomic to neuro-medicines and bio-engineering. and bioinformatic approaches. Also, Scientists gave focus on encompassing biomolecule mining from hitherto untapped molecular systems, cognitive and sources such as marine organisms and computational neuroscience and work on plants have been performed at NCCS that physiological processes that underpin the would aid in treatments of AIDS, diabetes, normal functioning of the brain as well as malaria and osteoporosis. major classes of brain disorders, such as neurodegenerative, neuro-oncological, The institute provides state of the art infective, developmental and neuropsy- infrastructure facilities to its scientists. As a chiatric ones. NBRC is also conducting part of this process, we have LC-MS, research on infectious agents including MALDI-TOF, Confocal and high throughput Japanese encephalitis, HIV and Prion

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diseases. As neuron-glia crosstalk is Alzheimer’s disease. Image-guided therapy recognized to be pivotal to normal brain of stroke and vascular dementia has been functions, the NeuroAIDS laboratory has optimized. Work pursued on broken new ground by establishing a well neurospectroscopy has broken new grounds characterized human neuron-glia co-culture in the measurement of metabolites in the system that is used for unravelling brain as regards sensitivity and specificity intricacies of neuron-glia communication. and is being used to answer questions of Researchers are expected to develop biological relevance. The Speech and capabilities with human brain cell culture Language Laboratory (SALLY), which has system to better understand HIV-1 proteins been investigating the development of modulate neurocognitive functions in HIV/ cortical circuits for reading two languages AIDS patients. (English and Hindi) that differ in script and orthography (sound-letter mapping), has Importantly, NBRC’s endeavor from the “the shown the existence of distinct reading bench to the bedside” has finally become a circuits for the two languages. reality. Leads of the scientific discoveries that minocycline can be used for the New initiatives taken during the year treatment of Japanese Encephalitis has been cleared by the Drug Controller General of A Centre for Excellence in Epilepsy centred India for a Phase II clinical trial at CSM round a Magnetoencephalogram (MEG) has Medical University, Lucknow. Research been initiated in NBRC in collaboration with group investigating the pathogenesis of AIIMS. Investigators from both AIIMS and Angelman’s syndrome has found that NBRC would be using this equipment, chronic stress due to altered glucocorticoid which would also be developed as a receptor signalling might lead to cognitive National Facility for use in a wide variety deficits and anxiety-like behaviour in a of disorders in addition to epilepsy studies mouse model of Angelman’s syndrome. as well as in the study of normal functioning of the brain. Faculty is focussing work on translational neuroscience and computational National Program on Perception neuroimaging and has developed new Engineering methodologies including energy flow mapping and thermal conduction tensor A programme was undertaken to develop imaging to predict the occurrence of technology inspired by the brain

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mechanisms of perception by involving Centre for DNA Fingerprinting collaborations between NBRC and engineers and Diagnostics (CDFD), and cognitive scientists from seven institutes Hyderabad across the country with the funding of the Department of Information Technology. The CDFD has provided services in the areas of goal of multidisciplinary program are DNA fingerprinting and diagnostics testing investigations on the fundamental issues of for genetic disorders and also pursued perception and cognition, development of various research aspects in molecular models of perceptual and cognitive processes for technology development and biology. generate know-how for new information and communication technologies motivated by Services the models of perceptual & cognitive processes. The institute has also undertaken DNA Profiling: DNA profiling services, 112 various Bilateral/ Multilateral Agreements cases were forwarded to CDFD by the with the United States, Japan, Italy, The judiciary and law enforcing agencies out of Netherlands, Canada for joint R&D and which majority were related to identification networking of research. of the deceased (57) and maternity/ paternity disputes (40) and 14 states of the Further details may be seen on the website country availed DNA fingerprinting services www.nbrc.ac.in. of CDFD. Rajasthan forwarded 37 cases,

Fig 10.2: Details of the state-wise cases received

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followed by 18 cases from Uttar Pradesh, counselling to patients (as part of its efforts 16 from Andhra Pradesh, and 10 cases each to undertake research in the area of from Karnataka and Punjab (Fig. 10.2). Mendelian genetic disorders in humans) has Training on DNA fingerprinting examination successfully dealt with about 1650 cases this was provided to personnel from the State year. Forensic Science Laboratory, Uttar Pradesh and Andhra Pradesh medical College, New initiative taken on established of The Visakhapatnam. Medical Genetics Unit at Nizam’s Institute of Medical Sciences, Hyderabad. The unit New initiatives taken in DNA profiling for has been operating successfully to offer providing services to demonstrate the power outpatient referral services, and the process of expanded application of the technology of creating a Department of Medical improving the system of criminal justice Genetics for undertaking research and delivery in the country. An MoU was signed superspecialty training programs in clinical with Institute of Life Sciences (ILS), genetics. An application to Medical Council Bhubaneswar and State Government of of India has been submitted by the CDFD Orissa, to establish its laboratory in ILS and to that effect. participate with the Govt. of Orissa to provide DNA profiling services. APEDA-CDFD Centre for Basmati DNA Analysis: Based on one of the DNA Diagnostics: The Diagnostics Division is inventions developed and patented by the providing genetic evaluation and Centre, the Agricultural Products Export

Genetic investigations done during the year Investigation Total cases Positives Cytogenetics 774 77 (9.9%) Proband 695 72 (10.3%) Prenatal 79 5 (6.3%) Molecular Genetics 593 254 (42.8%) Proband 565 247 (43.7%) Prenatal 28 7 (25 %) Biochemical Genetics 655 167 (25.5%) Proband 640 162 (25.3%) Prenatal 15 5 (33.3%)

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Development Authority (APEDA) of the modern biology, with a group of Govt. of India has entrusted CDFD with the approximately twenty faculty-level scientists. task of certifying the quality and The major thrust areas include authenticity of basmati rice. During 2011, computational biology and bioinformatics, 205 basmati samples were analyzed. Since structural and molecular biology, genetics the testing was introduced about 7 years and epigenetics, silkmoth genomics, ago, the proportion and magnitude of molecular pathogenesis, cancer and stem cell adulteration has progressively decreased - biology, molecular and cellular biology, attesting to its deterrent value. fundamental studies on transcription and signal transduction, and plant biology. A Research glimpse of research activities at CDFD are given below: The institute has taken up various research and developmental activities during the year Silkmoth Genetics and Genomics: The and pursued several frontier areas of Centre has identified and characterised sex

Fig. 10.3: Model explaining the mode of action of two BmDsx proteins in females. A) Two different regulatory elements (RE) are present in the promoters of downstream target genes (vitellogenin, SP1-Storage Protein and PBP-Pheromone Binding Protein). Homodimers of BmDsx bind separately to these regulatory elements to independently regulate them. B) alternatively, heterodimers of BmDsx bind to the single regulatory element present in the promoters of downstream target genes to regulate their expression. Products of intersex gene may also possibly interact with BmDsx.

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determining genes – the homologs of microarray data revealed that out of the doublesex (dsx) and intersex (ix) genes in 240,000 probes, approximately 2400 probes Bombyx mori as well as in wild silkmoths, are enriched for binding. Gene-based Antheraea assama and A. mylitta (Fig. 10.3). enrichment showed that this corresponds The group has identified four B. mori to 357 genes out of the ~4000 genes in the nucleopolyhedrosis virus encoded miRNAs genome of M. tuberculosis. An interesting using a combination of in silico and outcome of this analysis was that the experimental methods and has GroEL1 binds predominantly to the coding computationally predicted 8 viral and 64 region, and to GC-rich regions. Enrichment cellular targets of these virus-encoded in the coding region of the PE-PGRS genes miRNAs. The putative functions of these was also observed. The results of ChIP- targets suggest a key role of viral miRNAs chip were confirmed by PCR amplifications in insect-pathogen interactions by of the bound probes, and by modulating several viral replication genes electrophoretic mobility shift assays of as well as those involved in host immune identified consensus sequences. These defense machinery (Fig. 10.4). results were further confirmed by Surface Plasmon Resonance with the oligonucleotide sequences designed using the consensus obtained from ChIP-chip analyses.

Bacterial Genetics: Through the Centre’s work in the area of Bacterial Genetics, a role for NusA in Rho-dependent transcription termination in Escherichia coli has been demonstrated, and a model has been proposed for modulation of the termination mechanism by the H-NS family

Fig. 10.4: Schematic overview of the role of miRNAs in of nucleoid proteins. R-loops formed in host virus interaction. strains defective for Rho-dependent Structural Biology: The Centre has carried termination appear to provide a bypass out ChIP-chip experiments in Mycobacterium mechanism for the absence of two pathways tuberculosis using monoclonal antibody of RNase E. Finally, several new targets of raised against GroEL-1. The analysis of the ArgP transcriptional regulator have been

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identified, including lysP, dapD, asd, lysA, Transcription: CDFD has been engaged in and lysC (Fig. 10.5). understanding the molecular basis of factor- dependent transcription termination and antitermination in Escherichia coli and has been able to demonstrate the generalized existence of kinetic-coupling in the Rho- dependent transcription termination. Studies have shown the requirement of nascent RNA in the recruitment of Rho to the elongation complex. The group has proposed an inhibition/antitermination hybrid model for overcoming the Rho-dependent termination by N (Fig. 10.6).

Fig. 10.5: Spectrum of Rho-dependent transcription termination efficiencies in different mutants, and the effects of H-NSÄ64 or YdgT thereon. The designations Cell Signalling: The Centre has been rho, nusG and nusA without suffixes refer, respectively, to rho-A243E, nusG-G146D, and nusA-R258C mutations. studying the regulation of eukaryotic cell

Fig. 10.6: Possible mechanisms of overcoming the Rho-dependent termination by N.

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physiology by inositol pyrophosphates. Mammalian Genetics, Molecular Oncology Yeast lacking inositol pyrophosphates and Immunology: Laboratory of Mammalian display defects in ribosome biogenesis, Genetics has shown that a strong correlation reflecting the regulation of rRNA exists between the DNA methyltransferase transcription by IP7. Gene expression DNMT3L involved in epigenetic analysis of mammalian cells with reduced reprogramming and carcinogenesis unlike

IP7 has led to the identification of a role for other DNA methyltransferases, Dnmt2 has inositol pyrophosphates in regulating actin been shown to be involved in RNA cytoskeleton dynamics and cell migration. processing during cellular stress. Results from the Molecular Oncology group of the Computational Biology, Bioinformatics and Centre have provided insight into the Functional Genomics: The major activity of distinct clinical behaviour of early-onset computational biology group at CDFD rectal cancer. ARID1B, a component of the pertains to analyses of protein-protein SWI/SNF chromatin remodelling complex interactions under different contexts such has been shown to be likely novel tumor as role of intrinsically disordered proteins suppressor gene for pancreatic cancer. The in human-Virus (Hu-Vir) protein-protein Laboratory of Immunology has been involved interaction network, construction and in detecting the role of Ras and p53 on comparison of human tissue-wise protein- doxorubicin-mediated apoptosis (Fig. 10.7). protein interaction networks and structural and functional characterization of hubs in Plant-Microbe Interactions and Fungal human PPI network. A novel, high Pathogenesis: The researchers in the performing SVM-based method to predict Laboratory of Plant-Microbe Interactions are disease and neutral nsSNPs has been studying the dynamics of DSF mediated developed by the researchers in this group. quorum sensing in individual cells. A novel Projects related to identification and outer membrane localized adhesin, XadM, characterization of promoters and of Xanthomonas oryzae pv. oryzae, which is transcription factor binding sites in required for virulence has been isolated. A Mycobacterium tuberculosis, reconstruction of group has uncovered a novel role for a a genome-wide protein-protein functional glycosylphosphatidylinositol (GPI)-linked linkage map of Escherichia coli, and genome aspartyl protease, CgYps1, in the regulation analysis of Plasmodium falciparum to of pH homeostasis in C. glabrata under understand the effect of AT-richness on the acidic environmental conditions, a pre- proteome, have been carried out. requisite for survival in host niches of

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Fig. 10.7: Ras puts brake on doxorubicin-mediated cell death in p53 expressing cells. Doxorubicin induced more cell death in p53 negative cells (U-937, THP1, SKBr3, and HeLa) than p53 positive (MCF-7) cells as shown by Live&Dead assay (A). Doxorubicin increased p53 DNA binding in MCF-7, but not SKBr3 cells (B). Doxorubicin increased p53 DNA binding and p53 and p21 expression in HCT116 p53 positive cells (C). The expression of Fas increased, but K- ras decreased in p53 negative cells as shown by Western blot (D) and immunofluorescence study (E). Overexpression of wild type K-ras in p53 negative cells decreased basal expression of Fas (F). K-ras overexpressed p53 negative cells showed less sensitive to doxorubicin-mediated cell death (G)

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varied pH. A set of 102 genes in C. glabrata Genome Analysis and Molecular Mapping, which contribute to its survival/replication Molecular Mechanisms of Abiotic Stress in the intracellular milieu of macrophages Response, Nutritional Genomics, Plant have also been identified (Fig. 10.8). Development and Architecture, Plant Immunity, and other Emerging Areas. A National Institute of Plant bird’s-eye-view of some of the scientific Genome Research (NIPGR), New achievements of the Institute for the period Delhi under report is as follows:

The National Institute of Plant Genome Bioinformatics: facility at the Institute and Research (NIPGR) has taken up research has been strengthened. An automated programmes in Computational Biology, procedure was developed for identification

Fig. 10.8: A. Representative confocal images of Xoo biofilm formation on air-media inter phase on a glass slide. B. Average thickness of the biofilm formed by different strains of Xoo at different time points measured by confocal microscopy.

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of terpene synthase (TPS) or prenyl alexandrinum, a microsatellite enriched transferase (PT) proteins in plants using library was constructed which led to the Profile Hidden Markov Model. Efforts are development of 692 SSR markers. In the underway to predict the product specificity case of foxtail millet, 98 novel ILP markers of the newly identified TPSs through were developed using sequence information modeling and structure analyses. In the of rice. For periwinkle, a map of 8 linkage genome analysis programme, work was groups spanning 1790.4 cM and mean carried out for understanding within the distance between 172 markers of 10.34 cM chickpea. For this, deep sequencing is being has been prepared. In order to gain done using various next generation functional and biological insights from the sequencing platforms. The 454 vastly growing plant genomic data, efforts pyrosequencing platform generated 8.53 Gb were made to identify microsatellites (or (27 million reads, 11.5X) of sequence data. SSR sequences) in available plant genomes Sequencing of 3 kb and 20 kb paired-end using the Mreps algorithm combined with libraries generated 1.34 Gb and 199 Mb customized perl scripts. sequences, respectively. Assembly of this data along with other data generated 492 The understanding of the molecular Mb (66% of the genome) assembled mechanisms of abiotic stress responses has sequence. The de novo assembly and improved. In rice, different experiments characterization of the chickpea revealed interactions of stress associated transcriptome revealed a total of 34,760 protein, OsSAP1, with OsRLCK253 and transcripts. The information on genome and OsSAP11 in the plasma membrane and transcriptome is helpful in the identification nucleus, respectively, and interaction of of genetic markers. In chickpea, interspecific OsSAP11 with OsRLCK253 at the nuclear linkage map has been constructed for ICCV- and plasma membranes. Also, transcripts of 2 x JG-62 using 522 STMS markers, and for several transcription factors were found to ICC4958 x PI489777 using 735 EST based be up-regulated during water-deficit and markers along with 278 genomic STMS high salinity stress conditions. Few of them, markers. including two belonging to homeobox family, are being investigated for their In the Indo-Canadian Pulse Genomics function. An interactome map between Initiative, a total of 536 SSR primers were OsMPKs (MAP kinases) and OsMKKs (MAP designed from lentil, of which 196 were kinase kinase) was generated. It was validated. In another legume Trifolium observed that in rice, induction of

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phytoalexin biosynthesis genes by UV-B rays urinary tract calculi, hyperoxaluria, was linked with the activation of MAP hypocalcimia, and nephrolithiais. The OXDC kinase. Study with a core set of foxtail millet gene encoding oxalate decarboxylase from cultivars suggested that drought tolerant wood-rotting fungus Flammulina velutipes was cultivars possess a wider array of introduced into tomato, spinach, and antioxidant machinery with an efficient soybean to reduce their oxalate content. The ascorbate-glutathione pathway. cDNAs transgenic grasspea over-expressing OXDC coding for putative dehydration responsive gene, to make it edible by reducing the element binding protein, SiDREB2, and a associated neurotoxin risk factor, has been salt-stress related NAC protein, SiNAC, were raised. Few important glucosinolate characterized from foxtail millet. Using biosynthesis genes like MYB28, CYP83A1, heterologous systems, it was shown that and GSL-ELONG were isolated and CaZF, a C2H2 zinc finger protein from characterized from Brassica juncea with the chickpea, improved salt stress tolerance in ultimate objective of reducing glucosinolate yeast and tobacco. The transgenic tobacco content. lines overexpressing CaZF produced phenotypes like improved root and shoot In the field of plant development and growth along with stress tolerance. Two architecture, NIPGR has contributed stress-inducible promoters were also significantly. Investigation of Z-box specific evaluated for their activity and raising transcription factors in light signaling transgenics with selected target genes. pathways revealed that ZBF2/GBF1 is a negative regulator in light mediated In the nutritional genomics programme, with inhibition of hypocotyl elongation, whereas the objective to increase the shelf life of HY5 positively regulates photomorphogenic fruits and vegetables, the N-glycan growth in various wavelengths of light. processing enzymes á-D-mannosidase and Experiments designed to study crosstalk â-hexosaminidase were silenced to decrease between different plant hormone responses and delay the fruit softening in tomato and suggested that brassinosteroid induced capsicum. In an effort to increase the randomized growth of dark-grown seedling nutritional value of crops, stable lines of hypocotyls was facilitated by auxin and AmA1 potato developed were grown and antagonized by ethylene. Glucose was evaluated. The transgenic potatoes have found to affect most of the important genes increased protein content and are safe for involved in cytokinin biosynthesis, consumption. Oxalate is a major factor in perception and signaling. In rice, functional

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analyses of seed-specific genes and anther- papers. In the same period, three patents specific gene promoters are going on with were filed and two technologies developed a view to understand the crucial controls of at the Institute were transferred for product reproductive development connected to the development. A Plant Growth Facility has yield. For the first time, in Pisum sativum, also been activated. The research details of the structure and function of programmes at NIPGR are aimed to stipules were explored and it was found improve the yield and quality along with that the stipules share anatomical features protection of loss due to stress. The ongoing of leaves but have better hydraulics. In activities at NIPGR will contribute Arabidopsis, it was found that tasiRNAs might significantly to achieve these objectives. The be regulating root architecture by Institute is now looking forward towards modulating different ARFs and some new horizons in the field of Translational miRNAs. Research, Plant development & Nutrition and Seed Biology. Microarray analysis on differential transcriptome of chickepea-Fusarium Institute of Life Sciences (ILS) interaction was performed, and a gene regulatory network specific to disease vs. The institute continued research on three immune pathway was constructed. To areas centered around infectious diseases understand the early responses elicited by biology, gene function as well as regulation chickpea blight fungus Ascochyta rabiei, PCR and translational research through based suppression subtractive hybridization technology development. (SSH) strategy was used to isolate early responsive genes of chickpea. In A. rabiei, Infectious disease biology: Work on analyses of differential expression of several identification and characterization of an genes after oxidative stress treatment led to immunoregulatory helminth glycoprotein the cloning and characterization of OYE, was taken to its logical end. The active AOX and YAP1 genes. In soybean, it was moiety that binds to TLR4 on the surface of demonstrated that the resistance against mononuclear cells and inhibits endotoxemia MYMIV was due to an enhanced viral origin in animals was identified to be a of replication-specific siRNA accumulation hexasaccharide, Chitohexose (Fig 10.9). This and DNA methylation. also offered insights into evolutionary relationship between nematodes and sepsis During the period of report, NIPGR in human population. The research on TLR researchers published 61 high impact

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polymorphism in human filariasis revealed These findings shed light on the molecular an association of TLR2 mutants (ins/ del + efficiencies of pathogenic isolates of V. del/ del) and minor allele (del) for increased cholerae harbouring natural variants of ctxB risk of elephantiasis development. in causing the disease, suggesting the need to consider ctxB variants in designing

Fig 10.9: In silico analysis of interaction between chtx and TLR4- three dimensional molecular docking between chtx and extra cellular domain of mouse TLR 4 was performed using patch dock software demonstrating the interaction of chtx to the internal pocket of extra cellular domain of TLR4.

Studies undertaken on pathogen vibrio vaccines against cholera. isolates have revealed details of genes regulating toxicity and virulence and ability Gene regulation and function: to form biofilms. Molecular analysis of toxigenic V. cholerae strains indicated the To understand the progression of cancers presence of multiple ctxB genotypes. The in general and Chronic Myeloid Leukemia comparative modelling approach to define in particular attempts were made with the structural features of all known variants newer technologies and discoveries such as of ctxB found in V. cholerae including 0139 micro RNA to understand the role of serotypes suggested subtle variations in the miRNA in CML cases both during blast binding ability of ctxB variants to crisis and in chronic phase. The studies on carbohydrate ligands of GM1 viz. galactose, consequences of post translational sialic acid and N-acetyl galactosamine. modification (acetylation) of the proto

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oncogene EVI1 in case of CML revealed expressing antibacterial peptides as dressing that EVI1 binds to SIRT1 promoter element material for wound healing and burns. A and up regulates SIRT1 transactivity which third approach is to acquire insights into triggers deacetylation and degradation of genes that are associated with development EVI1 and in term can regulate p53 activity. of tolerance to abiotic stress such as high Metagenomics is evolving into a promising salts by cloning and sequencing ESTs of area of research along with bioprospecting several genes using S.maritima as a model of extremophilic bacteria. Several novel plant. extremophilic organisms have been isolated and identified at ILS. Characterization of Translational research and Technology their house keeping genes and their Development expression in plant systems are expected offer interesting opportunities. Nano targeting of Gemsitamine the drug of choice for pancreatic cancer is being Work was pursued at ILS towards attempted in a xenotransplant model in generation of transgenic plants with catalase- SCID mice and early results have shown antioxidant enzyme that significantly promise. The next logical step will be contributes to plant growth, survival and undertaking clinical trial for pancreatic crop yield. In order to obtain a proof of cancer which has a very poor prognosis. principle for the above, transgenic Significant progress have also been made Arabidopsis plants with mutant Catalase in the synthesis of amphiphilic polymer gene have been generated. Moving this coated MNPs which provides the platform approach to Rice plant will be the natural for in vitro as well as in vivo studies of step forward. Another potential way to make drug delivery into brain in case of brain plants resist pest will be to enhance their tumor and or cancer. innate immunity. Introduction of genes of innate immunity of higher organisms such Institute of Bioresources and as human or murine defensins into plants Sustainable Development (IBSD), using high expression promoters is another Imphal issue being pursued. Generation of several plant promoters by DNA shuffling Institute of Bio-resources and Sustainable has been a major activity in ILS in this Development (IBSD), Imphal has continued direction. The spinoff from this study its efforts on sustainable utilization of is the possible use of plant extracts bioresources focusing on medicinal,

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aromatic and horticultural plants, microbial, such novel fibrinolytic enzyme were also aquatic and insect bioresources toward carried out. A total of 1857 bacterial strains economic development of North East from NE region soil have been found to Region. Significant achievements during the exhibit anti-cancer, anti-diabetic and anti- year are summarized below: inflammatory property. About 100 cellulolytic isolates across six sites of NE Medicinal, Aromatic and Horticultural region, high level of cellulase activity (3.815 Plant Resources μg/ml/min) was detected in their culture filtrates. A microalgae repository with over Petroleum ether extract of Oroxylum 2000 isolates has been established at the indicum was found to exhibit high level of institute. Two isolates of Enterobacter sp cytotoxic effect and apoptosis on Hela cells. have been found to stimulate seed Germplasm repository of Zingiberales has germination and seedling growth in been further enriched by addition of 27 mandarin orange. Bio-pesticide formulations more species raising the collection to 289 comprising Trichoderma sp T-86 and accessions belonging to 73 species. Pseudomonas fluorescent IE 161 strains has Bambusa manipureana and Dendrocalamus been tested at field level for the control of hamiltoni have been selected as superior soft rot disease in ginger. edible bamboo due to their low cynogenic glycosides content, high antioxidant Aquatic and Insect Bioresources properties and high level of nutrient content. Kachai lemon found as a potential Seed production technology of two root stock for production of budded indigenous ornamental fishes developed and mandarin orange, to increase yield, reduce formulated low cost feed using Rice bran: moisture stress and Phytophthora disease mustard cake: silkworm pupae waste with incidence. different proportions shown promising results. Microbial Resources Bio-resource Database Unit A strain of Bacillus subtilis MTCC 548 from fermented soybean was found to exhibit Two software programs (SSRIST-for analysis very high fibrinolytic casenolytic ratio of Simple sequence Repeats, GLogo- indicating high affinity to fibrin. Production, genome sequence logo representation) extraction and purification process of four developed. Databases on Zingiberaceae,

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North-Eastern Human Resources, Bamboo using IBSD starter cultures organized in and Orchids have been updated. collaboration with Krishi Vigyan Kendra, Imphal. Human Resources Development Rajiv Gandhi Centre for Currently, 16 Ph.D. - JRFs, 7 Post-doctoral Biotechnology (RGCB), fellows and 40 project staffs are working at Thiruvananthapuram the institute. A total of 30 trainees from different institutes of NE region have been The major emphasis of the RGCB is on imparted training in various areas. research programs looking at the Disease Biology and Molecular Medicine. Regional Centre of IBSD in Sikkim Employing cutting edge technologies, they explore the biological systems with a Germplasm of various medicinal plants and mission to understand the diseases large cardamom (Amomum subulatum) processes focusing on cancer, infectious collected from different locations of Sikkim diseases, neuronal disorders, reproductive Himalayas maintained in the Centre. Further and cardiovascular diseases. The ultimate work on ginsenoside biosynthetic pathway, aim is to understand the molecular marker development and cell cultures of mechanisms, facilitating development of Panax is in progress. Strain of Colletotrichum novel diagnostics and therapeutics. Equal gloeosporioides, the fungal blight pathogen emphasis is given to understand the host- of large cardamom isolated in pure form. pathogen interactions in spices to develop 28 actinomycetes and 61 indigenous sustainable method to improve product bacterial isolates have been isolated from quality. rhizosphere soil of large cardamom plants. Disease Biology Center of Diabetes: RGCB Outreach programme began a new program in disease biology of diabetes by taking up the management of A low cost technique for conversion of the Institute of Diabetes, a specialty medical floating aquatic biomasss of Loktak Lake center belonging to the Government of into compost demonstrated to farming Kerala. This will allow RGCB access to community of Bishnupur district. A well-established facilities that will Training-cum-Demonstration Programme on eventually form the nucleus of an advanced fermented soybean production technology center for chronic disease biology.

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Drug-induced Senescence Generates state to a low ROS proliferating stage in Chemoresistant Stem-like Cells with drug-induced tumor stem cell enrichment. Low Reactive Oxygen Species Differential gene expression in breast A study provides evidence for the rare tumor tissue at different stages of escape of tumor cells from drug-induced menstrual cycle: Special emphasis on cell death, after an intermediate stay in a timing of breast cancer surgery and non-cycling senescent stage followed by prognosis unstable multiplication characterized by spontaneous cell death. However, some Apprehensions are high that dispersal of cells appear to escape and generate stable tumor cells to the other parts of the body colonies with an aggressive tumor stem cell- during a breast surgery depends on the like phenotype. These cells displayed phase of menstrual cycle the patient is in. higher CD133 and Oct-4 expression. If genes involved in various aspects of Notably, the drug-selected cells that carcinogenesis are hormonally regulated, contained low levels of reactive oxygen modulation of their expression at specific species (ROS) also showed an increase in phases of the menstrual cycle might antioxidant enzymes. Consistent with this predispose seeding of cancer cells towards in vitro experimental data, RGCB scientists faster growth rate or of increased metastatic observed lower levels of ROS in breast potential. The scientists at RGCB are aiming tumors obtained after neoadjuvant to understand at the gene level, if timing of chemotherapy compared with samples that surgery during a particular phase of the did not receive preoperative chemotherapy. menstrual cycle plays a significant role in These latter tissues also expressed enhanced survival of a pre-menopausal woman with levels of ROS defenses with enhanced breast cancer finding important molecular expression of superoxide dismutase. Higher events/ patterns that occur might help to levels of Oct-4 and CD133 were also determine a long term prognosis by observed in tumors obtained after appropriately timing the surgery and hence neoadjuvant chemotherapy. Further studies save lives. By Microarray studies, a number provided evidence for the stabilization of of genes which had protective effect were Nrf2 due to reduced 26 S proteasome up regulated in luteal phase with respect activity and increased p21 association as to that in the follicular phase. Some of the the driving signaling event that contributes significant ones include CDH: (a gene to the transition from a high ROS quiescent involved in cell adhesion was up regulated

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by 4 fold), ING1: (a tumor suppressor that have identified a secretory factor, induces cell growth arrest and apoptosis Cyclophilin A, a peptidyl prolyl cis trans was up regulated by 6 fold), KRT8: (a gene isomerase in monocytic cells of THP-1 cells known to maintain cell integrity and cell as well as from patients with Type 2 differentiation was up regulated by 2 fold), Diabetes Mellitus which is released by CST6: (with an anti-metastatic function was monocytes in response to oxidative stress found to be up regulated by 3.4 fold). Genes induced by hyperglycemia. Cyclophilin A which are normally expressed in during (CyPA) is known to have paracrine and tumor progression such as MUC-1, VIM, autocrine stimulatory effect on endothelial CTSD, and CTSB were notably cells. CyPA secreted by monocytes could downregulated. have important effects on enhancing monocyte adhesion to endothelial cells and Proteomic analysis of circulating cells thus in the pathogenesis of atherosclerosis for the discovery of biomarkers of in type 2 diabetes. increased risk of atherosclerosis in patients with type 2 diabetes mellitus Molecular Typing of local isolates of Chikungunya Virus: Identification of Endothelial dysfunction, diabetic mutant strains with potential for dyslipidemia, hypercoagulability, impaired transovarian transmission in mosquitoes fibrinolysis, platelet hyperaggregability, oxidative stress, autonomic neuropathy, A number of novel mutations, in both toxic effects of hyperglycemia all contribute structural and non-structural protein coding to the mechanisms of increased risk of regions, were identified in CHIKV isolates atherosclerosis in Type 2 diabetes. between 2006 and 2008 from Kerala by Hyperglycaemia may induce a chronic whole genome sequence analysis. inflammatory state in the vessel wall, thus Subsequently, these strains were identified accelerating the development of to have varying levels in vitro infectivity in macrovascular complications. It is speculated cell lines originated from different tissues. that the circulating monocytes may secrete While studying a CHIKV outbreak in 2009 specific proteins that could serve as in Northern Kerala, RGCB scientists individual markers or define a characteristic identified a novel strain of the virus with profile. Changes in the normal physiology specific mutations in the E2 protein (L210Q). of proteins that are relevant to It could detect the possibility of trans- atherogenesis, may promote atherosclerosis ovarian transmission of this virus strain in in patients with type 2 diabetes. Scientists mosquitoes. This observation, was

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subsequently supported from studies in cellular processes. Several projects are being other laboratories, can have significant pursued collaboratively. They are: a) epidemiological implications during CHIKV Protein-protein interactions b) Quiescence outbreaks. Recently, they have expressed and cell cycle c) Signaling pathways d) and purified the recombinant envelope Embryonic stem (ES) cell self-renewal e) proteins E1 and E2 from local CHIKV RNA biology f) Chromatin biology and isolates for diagnostics development and for regulatory networks. use in studies on viral pathogenesis. The institute is also providing service facilities Model Systems of excellence for molecular Diagnostics for infectious diseases, cancer and Lower organisms can regenerate their entire cardiovascular disease, DNA Fingerprinting body, a property that is lost in higher to cater to social & criminal justice animals including humans. If they can systems and DNA Barcoding for Plants and understand the cellular and molecular basis Wildlife for the regenerative capacity of these model organisms such as Hydra and NEW INSTITUTIONS/CENTRES Planaria, they may be able to use this knowledge in two ways: i) to develop Institute of Stem Cell Biology methods for augmenting the limited and Regenerative Medicine regenerative ability of human tissues/ (InStem), Bangalore organs; ii) to screen for drugs/small molecules that will assist research and The objective of the institute is to build a therapy in regeneration; iii) Cardiac strong foundation for core research and hypertrophy & induced pluripotent stem educational activities in the area of stem (iPS) cell core: In this program, core InStem cell biology and regeneration. Various scientists are collaborating with scientists activities undertaken include: and clinicians internationally and within India to work on cardiac function, iPS Basic Biology technology, biophysics and cell biology to tackle a core problem-generating cellular This core scientific program was initiated models of cardiac disease; iv) Epithelial with the appreciation that understanding biology and molecular oncology: The focus stem cell functions will require fundamental of the team is on epithelial stem cells and investigations into basic, molecular and development, mechanisms of tumor

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formation and networks that control MOUs signed, joint programs signaling and adhesion in tissue architecture. The MOUs and joint programs have been signed with California Institute for Research Infrastructure Regenerative Medicine, California; Cambridge University and NCBS for joint The research infrastructure at inStem is research interactions; FIRC Institute of being established gradually and by mid Molecular Oncology in Milan for joint 2012, their new space will be ready with research laboratory at InStem; iCeMS, Kyoto clean rooms for ESC, iPSCs, adult stem cell for joint research laboratory at InStem and culture, model organism labs & state of the Stempeutics for research in mesenchymal art molecular and cell biology facilities, stem cells. including office space for 10 PIs. Integration of CMC-DBT Center for Stem Cell Research at CMC, Vellore New research groups

CMC-DBT Center for Stem Cell Research An active recruitment process has resulted (CSCR) was established in 2005 as in hiring of two outstanding researchers who collaboration between DBT and CMC will build groups in basic biology of stem Vellore. Now this Centre has been integrated cells. with inStem as its translational unit through a MoU. inStem and CSCR will work closely Collaborative Science Chairs on various aspects of stem cella and regenerative medicine. Collaborative Science Chairs are accomplished leaders in their field of Centre for Molecular Medicine (IFoM) research, and have permanent faculty positions in a foreign institution. They are InStem have recently entered into an committed to working on collaborative agreement with the FIRC Institute of projects with scientists at InStem which Molecular Oncology in Milan for a new extend the scope of the host laboratories venture on cancer research. Co-funded by significantly. This program permits inStem both institutions, the collaboration will be to attract senior leading scientists to the effected by an inStem-IFOM Joint Research environment for a collaborative engagement Laboratory at inStem. Research fields of that covers particular interest for the Laboratory include

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cancer epigenetics, stem cell research, develop novel vaccines and biologics. chromatin dynamics, virology and Under the vaccine development program, computational biology.Recruitment of a phase III trial of an oral rotavirus vaccine group leader to this program will be 116E is carrying out at VIDRC. Research undertaken via a joint process. programme pursued developing a novel vaccine delivery vectors. THSTI and IAVI Translational Health Science and have entered in to a collaboration agreement Technology Institute (THSTI), focussing on a cross section study to screen Gurgaon for and generate broadly neutralizing monoclonal antibodies from HIV infected THSTI is an autonomous institution individual. The centre is also focussing on established by the Department of development of animal models, Biotechnology. The institute is designed to and understanding the natural history of be a dynamic and interactive organization disease in population giving new insights with a mission to conduct innovative into protective host responses and translational research and develop research biomarker discovery for screening vaccine collaborations across disciplines and candidates. professions to accelerate the development of concepts into tangible products to Paediatric Biology Centre (PBC) improve human health. The institute presently focusses research activities in three This centre is undertaking studies on human broad areas, for which three centres have been established namely, (i) vaccine and perinatal biology including maternal, fetal, infectious diseases centre, (ii) paediatric neonatal and childhood infections, biology centre, and (iii) centre for bio design nutritional biology and other childhood and diagnostics development. A Clinical illness. The research activities have been Development Services Agency (CDSA) has developed as domain programs in been established as an extra-mural Centre immunobiology of perinatal period, the of THSTI. biology of vaccine immunogenicity in Indian infants, molecular biology of specific Vaccine and Infectious Disease paediatric diseases and innovative Research Centre (VIDRC) technologies for newborn and child health. The core research programme is focusing VIDRC conducts basic and clinical research on immunological characterisation of to advance translatable knowledge to leucocytes in human cord blood and early

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infancy. Work on evaluating the ability of regulatory product evaluations through a novel safe adjuvants like Vitamin D to comprehensive and sustained training enhance the quality and duration of program. It proposes to establish a network systemic immune responses to antigens of institutions by supporting good existing including the Inactivated Polio Virus (IPV) centres and upgrade them as centres of vaccine and its ability to generate priming excellence (COE) for training and regulatory at mucosal sites to cutaneously delivered trials as affiliates of CDSA. It will enter vaccines was carried out. A multicentre into collaborative agreements with at least study has been initiated to develop a rapid five premier institutions in the first year to diagnostic test for diagnosis of celiac disease convert them into centres of excellence to (CD) by ICGEB, AIIMS and an industrial tap the huge potential of the clinical trials partner and the patent for the diagnostic kit market. CDSA will provide a core grant to has been filed. these institutions to develop human resource and infrastructure. CDSA has been Centre for Bio Design (CBD) interacting with national and international experts and institutions involved in CBD centre is engaged in creating medical technology innovation in India for affordable conduct of clinical trials to develop the health care and to support services that most appropriate training strategy. An extend from strategic bench work to alliance has been formed among commercialization and emphasis is given Departments of Health Research (DHR), on development of low cost, high Department of Biotechnology (DBT), and quality indigenous implants and devices. Ministry of Health and Family Welfare of CBD has initiated development of a the Government of India to support technology platform for efficient and fast research to generate evidence for generation of specific antibodies for various development of practical and scalable antigens. regimens to medically rehabilitate children suffering from Severe Acute Malnutrition Clinical Development Services Agency (SAM) without serious complications at (CDSA) home/community level and/or at peripheral inpatient facilities. DBT and CDSA is established as an extra mural unit CDSA have taken an effort to promote use of THSTI to develop a cadre of of zinc supplement for the treatment of investigators of global standard in childhood diarrhea.

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international institutions, including medical National Institute of Biomedical colleges and hospitals. NIBMG’s Ph.D. Genomics (NIBMG), Kalyani, programme is beginning to thrive; the West Bengal current strength of our research scholars is twelve and is growing. NIBMG was established in 2009 to provide an impetus to research and translation to The Institute has established a high- enable an understanding of the aetiologies, throughput DNA sequencing facility that prevention and treatment of diseases and a includes six next-generation DNA reduction in public health burden of our sequencers and a 96-capillary sequencer. A country. Inadequacy of formal training cell-biology laboratory has also been programmes in human genetics has been a established. The Institute’s flagship project, serious impediment to the development of the International Cancer Genome biomedical genetics in our country. NIBMG Consortium – India Project, is progressing is likely to be filled by initiating courses on well. This project attempts to identify genetics in medicine. genomic alterations that cause gingivo- buccal oral cancer, which has the highest NIBMG has been able to recruit the faculty prevalence in India, using massively-parallel and strengthen the facility. Two DBT- next-generation DNA sequencing NIBMG Fellows under Ramalingaswamy technologies. Fellows, four Young Biotechnologist Awardees, and one Clinical Research NIBMG has initiated a major population Associate have joined. The faculty members cohort study in the Kalyani area, to build a are currently engaged in research, training long-term cohort of 20000 individuals and and outreach programmes of the Institute. serial collection of biospecimens. Training Three core areas are developing in NIBMG and outreach programmes initiated and – cancer genomics; genomics of common conducted several workshops and seminars diseases and traits, including susceptibility in the Institute and have had visits by many to infections; and, statistical and population renowned scientists who have delivered genomics. The Institute has successfully seminars at the Institute. generated eight competitive extra-mural research grants, including one from the U.S. Construction of campus building on a 30- National Institutes of Health. Through these acre plot of land in Kalyani, has begun and research projects, NIBMG has developed expected to be completed in a period of 2 collaborations with many national and years.

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importance to be known as the Regional Centre for Biotechnology and Training and Education as Category-II institution under the auspices of UNESCO to undertake research in the field of biotechnology and to provide for matters connected therewith or incidentally thereto.

Regional Centre having the futuristic vision of making biotechnology education, training

Fig. 10.10: Professor Terry Speed, Head of and research is planned to be within Biotech Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Science yet broad-based and multi- Australia, and a member of NIBMG’s International disciplinary, its proposed research and Advisory Board, delivering a talk in the Institute educational activities being focused to be at the interface of different disciplines of Regional Centre for science with Biotechnology as a platform of Biotechnology (RCB), Gurgaon confluence. The institute is in the process of establishment of the labs and creating RCB is an Institute newly established by infrastructure for research and educational the Department of Biotechnology under the activities. While attempts are being made auspices of UNESCO. It is envisaged to be to establish a wide range of disciplines that an important member Institute of the include Biomedical Sciences, Bioengineering, Biotech Science Cluster (BSC) at Faridabad, Biochemical and Biophysical Sciences, NCR where construction activities are under Climate Science, Agriculture and progress. Presently it is undergoing different Environment, and Biotechnology Regulatory phases of growth. Currently, the centre is Affairs, IPR and Policy; a small beginning functioning from its interim laboratories at largely in the area of biomedical sciences 180, Udyog Vihar, Phase,-I, Gurgaon. has been made with the faculty members Hon’ble Minister, Science and Technology recruited. and Earth Sciences introduced a Bill (Item No. 27) during the Winter Session (9th The structural biology studies of regulatory Session of XV Lok Sabha) on 20th events in physiological processes focused December, 2011 to provide for the on immune recognition in the context of establishment of an institution of national antibody pluripotency and structural and

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molecular bases in host-pathogen occurrence of the thrombotic complications interactions. These studies have led to the in hemolytic disorders; more specifically, elucidation of the structural basis of mimicry how the binding of cell-free hemoglobin to of two chemically distinct molecules as seen the plasma protein von Willebrand factor by the immune system. This shows that makes them hyperreactive to culminate cell plasticity of antigen combining site of the adhesion and clot formation is being mature antibodies could enable addressed. On another front, that links more pluripotency even without any structural to the translational research, engineering of correlation of the binding antigens. nonmaterial for biomedical applications is Structural investigations of proteins being pursued. implicated in pilus assembly and biofilm formation of different bacteria toward Currently, seven members of the Faculty understanding bacterial infections and mode including the Executive Director, mainly of interactions with host are also being from biomedical sciences have made their respective laboratories functional. The pursued. Centre has been able to attract very smart fresh PhDs for young investigator The molecular mechanisms associated with programme and has started the training of cell division and intercellular students towards PhD degree. The Young communications including studies on the Investigator awardee, the Research spindle assembly checkpoint in metaphase, Associates, Junior Research Fellows and the terminal mitotic process of cytokinesis Trainees programmes have made a as well as analyses of the biogenesis and beginning with a potential to grow in the function of tunnelling nanotubes (TNTs) are times to come being studied. Molecular mechanisms in the ubiquitin mediated signaling in cellular The First meeting of the Programme pathways with focus being on the Advisory Committee was organized on 8th deubiquitination events are being explored. September, 2011 at RCB, Gurgaon under the Molecular mechanisms of infectious and Chairmanship of Prof K Vijayaraghavan, idiopathic inflammation relating to Director, NCBS, Bangalore. Broad vision of SUMOylation are being studied using S the Centre at the interface of multiple Typhi as a model organism. disciplines involving research and education covering diverse aspects of biotech sciences Molecular mechanisms of how intravascular as well as regulatory, IPR and policy issues hemolysis increases the severity and was discussed at length. An important

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recommendation that PAC made was establishing international connectivity by National Agri-Food organizing theme-based intense discussion Biotechnology Institute (NABI), meetings and workshops for enhancing Mohali, Punjab thinning capabilities. Meetings of the Executive Committee, Finance Sub- The institute has taken new Initiatives Committee and Board of Governors were during the year on studying the effect of also organized as per the schedule. diet and its constituents on adipogenesis.

Fig. 10.11: Researchers at RCB

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Fractionated constituents of selected cereal systems to crop species like wheat, legumes grains (wheat, finger millet, kodo millet and and vegetable crops. buck wheat) is being examined in human (preadipocytes/adipocytes) HPAd/HAd Nutrition and Processing Quality of and murine (3L3-L1 preadipocytes/ Wheat adipocytes) cell culture models and in-vivo diet-induced obese murine models to study Micronutrient and bioavailability the molecular basis of adipogenesis. enhancement

In an another study on targeted mutagenesis Iron transport from maternal tissues to for modification of plant genes to design endosperm in mature wheat seed using sequence specific zinc finger nucleases synchrotron radiation (ZFNs), synthetic proteins consisting of an engineered sequence specific zinc finger In wheat grains iron is located in outer layer, DNA-binding used to induce double- called bran and is lost substantially during stranded breaks (DSBs) in specific DNA milling and processing. Thus the flour is sequences and thereby promote site-specific almost devoid of iron. Understand the recombination and targeted manipulation of bottlenecks which prevent iron translocation genomic loci in a variety of different cell from the outer bran layers into the types is being deployed to target for gene endosperm in cereals, wheat grain with iron- modification of targeting novel traits in crop enriched endosperm is of great interest. The plants and to design arrays, improve study to understand the iron localization targeting efficiencies and eventually to and to identify the chemical form in which translate the information from model plant iron is present in different tissues of seed

Fig. 10.12

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and bottlenecks which prevent iron Microarray studies for processing translocation from the outer bran layers into quality the endosperm, X-ray Fluorescence (XRF) iron localization maps have been generated RNA was extracted from four wheat in grains of contrasting genotypes of wheat varieties-two good (C306 and Lok1) and two by using synchrotron powered beam line, poor chapatti (WH291 and Sonalika) making VESPERS (Very Sensitive Elemental and varieties at three developmental stages-7, Structural Probe Employing Radiation), at 14 and 28 DAA (days after anthesis). The Canadian Light Source, Saskatoon, Canada. RNA from the four varieties was hybridized Currently performing, micro-PIXE (Particle to Affymetrix wheat microarray containing induced x-ray emission) iron localization maps to generate and validate the iron in 25,000 unigenes. The hybridization data was different tissues of seed (Fig. 10.12). analyzed and a set of differentially expressed genes were identified between Gene discovery in wheat for good and poor chapatti varieties. improvement of processing quality Biochemical analysis of a few differentially expressed genes is being conducted to Multiplication of wheat germplasm validate the gene expression data. RNA was extracted from two soft wheat varieties 530 Indian wheat varieties are growing in (Naphal & Chinese Spring) and one hard three replications in RBD as well as augmented design at NABI research farm. (PBW 343) wheat varieties. The extracted 305 exotic and 312 wild wheat lines are RNA is being used for microarray-based maintained in three replicates in RBD design transcript studies. at NABI research farm. These germplasms were grown in this winter season for seed Database for grain hardness of Indian multiplication and nutrition and quality cultivars evaluations of a sub-set.

Studies on genes involved in grain hardness Screening of SSR markers e.g. Puroindoline were initiated to find out 110 SSR primer pairs were used for structure function relationship and screening to select polymorphic primers. involvement of different genes in grain Genotyping using SSR primer pairs is being hardness. Several new alleles were detected done. in the Indian germplasm.

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Development of virus induced gene which yielded very good and consistent silencing vector for wheat: Virus was results. detected from the wheat samples collected during 2010 and 2011. The whole genome Modifications have been done in viral of virus was sequenced and nucleotide genome by removing a small stretch of sequence of two clones has been submitted nucleotide (pathogenicity determinant to the GenBank. Phylogenetic analysis by region of the viral genome) and inserting nucleotide sequence of full-length genome multiple cloning sites (MCS) at the same of the virus revealed it was a novel positions. Visual marker gene phytoene mastrevirus (Family Geminiviridae) and is desaturase (PDS) is being cloned in being reported from India for the first time. modified VIGS vector and will be followed Infectious clone was made and tested for by making head-to-tail tandem repeat of the infectivity. Host range was determined by modified VIGS vector having PDS gene (Fig. infecting different Indian wheat varieties 10.13).

Fig. 10.13: A) Schematic representation of viral genome organization. B, C): modified viral genome and betasatellite having MCS for expression of foreign protein.

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Development of viral vector for A, B, C, D, E, F). Genetic transformation is transient expression being optimized from mature embryos and callus. GUS used as a reporter marker for The detected virus is mastrevirus and is the transient genetic transformation. known as monopartite geminivirus. Histochemical GUS assays were performed Association of betasatellite has been found after co-cultivation. Experiments are in for the first time with this virus and the progress to develop stable transgenic plants. same been confirmed by co-infectivity. Result of co-infectivity revealed that the betasatellite played a role of silencing suppressor by suppressing the host silencing machinery which resulted in accumulation of virus in host cell. Since, it is well known that a virus having silencing suppressor can be a good candidate for the expression of foreign proteins in plants and designed oligos to modify the viral genome and betasatellite for the transient expression of proteins (eg. GFP, udi or Zinc finger nuclease protein) of interest in wheat.

Fig. 10.14: Different stages of in-vitro regeneration of Genetic Transformation of Wheat and wheat plants and stable gene expression. A) Isolation of mature embryos used as explant, B) one month old Banana calli, C) two months old callus, D) and E) shoot induction and elongation, F) root formation G) transient expression of GUS in wheat callus, H) control plants with empty vector. Four cultivated varieties of wheat were examined for optimization of regeneration Accelerated Breeding for processing protocol. The embryos from mature seeds quality were cultured on MS medium containing different combinations and concentrations of For improvement of chapatti making quality, growth regulators. Best response for callus good chapatti making old cultivars (C306 induction was observed when embryos were and Lok1) were crossed with high yielding cultured on MS medium supplemented with recent cultivars (PBW343, PBW550 and 2, 4-D and Zeatin. Healthy roots were PBW621). Crossed seeds were backcrossed induced on the MS basal medium (Fig. 10.14 at DWR Regional Station, at Dalang Maidan,

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Lahaul, Himachal Pradesh in off-season. BC1 medium. However, efficiency and response

and F2 seeds have been sown in the field. for callus induction depends upon the For improvement of Biscuit making quality, cultivars. Grand Nain cultivar showed best major genes (Puroindoline and HMW response for callus formation. Optimization Glutenin genes) responsible for grain of ESC development has been initiated for softness were characterised in the selected the induction of embryos and genetic lines. For biscuit making quality, wheat transformation. landraces (NapHal and IITR67) were crossed with high yielding recent cultivars (PBW343, Quality and post-harvest stability of

PBW550 and PBW621). F1s were backcrossed farm produce

at Dalang Maidan in off season. BC1 and F2 seeds have been sown in field. For bread The research program on quality making quality wild species/genetic stocks enhancement and improving postharvest of Ag. elongatum, Ae. searsii and Ag. stability of fruits is focused on intermedium, are being utilized. Our goal is understanding biological basis of produce to transfer HMW-GS genes related to high quality and generating basic knowledge to grain strength from wild species to assist genetic and molecular manipulations chromosome 1A of wheat (translocation for better quality traits. The research work lines), as chromosome 1A of wheat has some has been initiated on mango and litchi fruits alleles that contribute negatively to bread during the period under report. making quality. . Mango: Research activities were carried out Establishment of embryogenic suspension to characterise the aroma-volatiles profiles culture (ESC) for genetic transformation of of mango fruit and to optimise method for Banana: Immature male flower buds of four rapid assessment of these compounds for cultivars (Grand Nain, Robusta, Nendran and developing biomarkers linked to fruit Dwarf Cavendish) were collected from quality and postharvest status. Static TNAU, Coimbatore. Immature male flower headspace (SHS) method was optimised for hands of rank 1 to 15 adjacent to the floral extraction of aroma volatiles and its efficacy apex were isolated and cultured on MS was compared with the widely used solid- medium containing several combinations phase micro extraction technique. The and concentrations of different growth improved SHS extraction technique was regulators for the optimization of protocol. combined with separation on different types Calli were formed on the callus forming of columns (polar and non-polar) and

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simultaneous detection using flame compounds. In Annona, flowers comprise ionization detector and mass spectrometer of a cluster of stamens (more than 200) and to achieve better resolution and detection carpels (more than 100). Each carpel has a of maximum number of compounds. single anatropous ovule that may develop into a single seed. The Annona fruit develops Litchi: Skin colouration in litchi is due to from the cluster of fertilized carpels, thus the presence of anthocyanin pigments the aggregate fruit contains several fruitlets. whose biosynthesis and postharvest Out of the multiple fruitlets a few fruitlets stability can seriously affect fruit quality. develop naturally, without seeds. The aim To develop better understanding of of the project is to understand the molecular anthocyanin biosynthesis at molecular basis of the development of seeded and level, litchi fruit (cvs. ‘Calcuttia’, ‘Dehradun’ seedless fruitlets in the same fruit of Annona and ‘Seedless’) sampled at different stages sp. Total RNA has been extracted from of maturation (green, colour break/pink, developing fruits of Annona squamosa, and red) were subjected to metabolic Annona chermola, Annona atemoya. Anatomical differences between seeded and seedless profiling and fingerprinting. Targeted and fruitlets during early stages of development untargeted analysis of metabolites from have been identified. Total RNA has been litchi aril and pulp has been carried out to extracted from developed and aborted seed give insights into dynamics of the of Annona squamosa. metabolites in relation to fruit maturation and ripening. Development of approaches for the Developmental Biology for Crop modulation of seedlessness, in the scion Improvement through rootstock signaling

Identification of genes responsible for The research project anticipates seedlessness in Annona fruits establishment of a technology which can lead to the development of a new approach to Seedlessness increases fruit acceptance by use transgenic rootstocks for delivering consumers due to several benefits: seedless specific siRNAs in non-transgenic scions for fruits are easier to eat and fruit processing the modification of economically important is easier. Also, seeds have bitter taste and traits. We are currently examining if siRNA in some instances, accumulate toxic based signalling can be applied to develop

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rootstocks which may influence seed for improving the draft assembly and development in the scion, grafted on to the scaffolding. Identified 90K putative SNPs stock using the model plant Arabidopsis by comparing inhouse generated thaliana. Developed transgenic lines transcriptome and publicly available ESTs constitutively expressing GUS reporter gene. till date. We are also identifying SNPs for Transgenic lines expressing double stranded genes expressed differentially on RNA- hairpin homologue of the reporter microarray of wheat varieties contrasting gene and target genes involved in seed for processing traits. Comparative Study development have been raised. of Triticum monococcum and Aegilops tauschii transcriptome has led to identification of Development of Genomic Resources for new transcripts after comparing with Grain Crops Unigene database (13620 for Triticum monococcum and 9950 for Genomic sequence data holds the promise Aegilops tauschii new transcripts). of dramatically advancing the Microarray data analysis and meta-profile understanding of basic plant science, and analysis of wheat expression array for of catalyzing practical advances in plant understanding the gene expression breeding. Genome data of wheat, Triticum dynamics in starch and sucrose aestivum, is available in public domain from metabolism pathway in genotypes with University of Bristol (5X coverage of contrasting baking, chapatti making and genome , ~200 million 454 reads). Genome biscuit making quality for mapping of data of the wild wheat, Aegilop tauschii, is differentially regulated genes on metabolic recently available from CSHL (Illumina pathways is under progress. reads). The studies undertaken for genome assembly and analysis to generate Development of genomic resources for framework map of wheat and to identify horticultural crops the vast majority of genes in three closely related progenitor genomes of wheat (AA, Germplasms collection of fruit crops is in AABB, and DD genome containing species) progress. About 35 cultivars of fruits and hexaploid wheat (Chinese Spring). Data belonging to 16 species have been collected from the above resources along with in- from different parts of India. The list of house data generated for transcriptomes of varieties/wild species collected and planted different germplasms at NABI will be used at NABI research farm is as below:

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• Annona squamosa, A. cheimoya, A. DBT, is being established within the campus reticulata, A. atemoya and some selections of University of Hyderabad, Hyderabad. such as NMK-1, Chandshila, Annona-2. NIAB has been registered as a society as • Banana: Grand Nain, Robusta, Nendran, per the Andhra Pradesh Government Act., Poovan, Rasthali, Red Banana, Ney 2001 (Act No. 35 of 2001) on 25th May, Poovan, Virupakashi, Karpuravalli, 2011 and started operating from an interim Dwarf Cavendish, Dwarf-Robusta, office building in the campus of University Udhayam and Nanjanagud-Rasabale of Hyderabad. To initiate R&D activities • Mango: Dashehri, Amrapalli, Mallika, NIAB has hired a building very close to the Langra, Chausa site allotted to NIAB. NIAB has initiated • Guava: Allahabad Safeda, Lalit, the recruitment process for scientific, Lucknow-49, Arka Mridula, Shweta technical and administrative positions. • Litchi: Calcuttia • Sapota: Cricket ball, DHF NIAB is designed to harness novel and • Citrus: Kinnow, Baramasi lemon, Citrus emerging biotechnologies and take up jambhiri, Jaffa Orange, Star Ruby grapefruit research in the cutting edge areas for improving animal health and productivity. • Pomegranate: Bhagwa The Institute’s focus of research will be on • Pear: Punjab Beauty, Patharnakh infectious diseases, breeding, reproduction • Plum: Kala Amritsari, Sutlej Purple and nutritional enrichment. The institute • Aonla: NA-6, 7, 10, Krishna aims at translational research leading to the • Bael: CISH-B1 and B2 development of novel vaccines, diagnostics and improved therapeutic molecules for Additionally, several germplasms have been farm animals. The Institute plans to promote collected such as wheat (>1500 lines), rice bio entrepreneurship by providing support (16 lines), pearl millet (4 lines), finger milet to commercial tenants involved in the (5 lines), mung and urd bean (26 lines), development of farm animal based sorghum (41 lines) and chickpea (9 lines). products.

National Institute of Animal BIO-CLUSTERS Biotechnology (NIAB), Hyderabad Biotech Science Cluster

National Institute of Animal Biotechnology The Department has established a Biotech (NIAB), a new autonomous institution of Science Cluster at NCR region of Delhi. The

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heads of four founding institutions namely, infections diseases, cancer, cell therapy and the National Institute of Immunology; the drug design. Regional Centre for Biotechnology; the Translational Health Science and Technology Bangalore Bio-cluster Institute and the National Institute for Plant Genome Research have signed a MoU to Bangalore Biocluster comprises the National create a new entity called the Cluster Board. Centre for Biological Sciences (NCBS), the The Cluster Board is an enabling mechanism Institute for Stem Cell Biology & by which these institutions, while Regenerative Medicine (InStem) and Centre maintaining their own autonomy of for Cellular and Molecular Platforms (C- governance, can address not only common CAMP). These three institutions are interacting, sharing knowledge and infrastructural and cluster-related resources on a regular basis to enrich administrative issues but also synergize research. C-CAMP is acting as provider, their complementary intellectual strengths developer and enabler of technology and facilities to create a seamless campus. development, scientific activity and This Cluster will coordinate the entrepreneurship. This is an institutional development of the new campus at model for cutting edge scientific research Faridabad. aimed at utilizing various centres of excellence for developing new hubs. InStem Efforts are being made to create this Cluster is developing collaborating programmes as a legal entity. A “Centre for Molecular with other institutes utilizing the Medicine” has been established at this infrastructure and facilities available in the Cluster. The focus of this Centre is on Cluster.

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284 Annual Report : 2011-12 Biotechnology Information SystemChapter Network 11

PUBLIC SECTOR UNDERTAKING

diversifying into other vaccine and Bharat Immunologicals & pharmaceuticals related to child health care Biologicals Corporation Limited, and marketing is being strengthened. Bulandshahar (BIBCOL)

New initiatives made to strengthen Research Bharat Immunologicals and Biologicals & Development and currently working on Corporation Limited (BIBCOL) was engaged solutions for treatment of several in formulating Oral Polio Vaccine (OPV), malnutrition among young children and located at Bulandshahar, Uttar Pradesh manufacturing facilities for oral solid doses towards eradication of Poliomyelitis in the form is being created for various products. country through Pulse Polio and routine A product sale is expected to touch around immunization programmes. As the Rs. 50 crores during the current year. For demand for OPV is in decline phase, successful management of Diarrhea & Mal BIBCOL added monovalent oral polio nutrition introduction of dispensable zinc vaccine mOPV -1, 2 & 3 in its product tablets and mineral vitamin mix portfolio, and efforts are on for introduction formulations is taken up. of bivalent OPV (1 & 3). In pharmaceutical sector, BIBCOL’s Zinc Dispersible Tablet has started gaining a major market share in public sector and a combo kit (Diarrhea Management Kit) for treatment of diarrhea among young children has been introduced in the market. The production has been optimized using the existing resources and reducing the dependency on a single product, by Fig. 11.1: Combo Kit – Treatment for Diarrhea

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established as part of IVCOL premises. Indian Vaccines Corporation Limited, Gurgaon Concerted efforts have been made to finalize the restructuring process with new The Indian Vaccines Corporation Limited activities. After taking necessary approvals (IVCOL) was started as a joint venture from competent authority the company has company in March, 1989 to undertake signed lease agreement with IPCL/Reliance research and development and manufacture Lifesciences, one of the promoters of the of viral vaccines. Due to change in product company, to initiate new activities including mix policy and non-availability of vero cell production of vaccines, biopharmaceuticals technology from Pasteur Merieux Serum & and set up superspeciality hospital to Vaccines (PMSV), France, the company was initiate translational research in collaboration on hold since February, 1992. In pursuance with NBRC. In order to initiate proposed of the Cabinet decision in September, 1998 activities Reliance Lifesciences (RLS) already restructuring process of the company has finalized the master plan for setting up been undertaken to utilize the assets created integrated life science unit alongwith super under the project. Accordingly, the National specialty hospital for neuro and cardio at Brain Research Centre (NBRC) has been Manesar, Haryana.

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286 Chapter 12

INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY

International Centre for Genetic Engineering immunogenicity of PfMSP119 as well as and Biotechnology (ICGEB), New Delhi has target another merozoite surface protein, made significant progress in the area of PfMSP3. infectious disease, agriculture and bio- energy during the year. Several new Programme has been initiated to understand initiatives were taken by sourcing funding the molecular basis of key mechanisms in from different agencies and from Bill Gates the biology of blood stage malaria parasite. Grand Challenge Exploration grant for the The program will undertake novel second phase of research. interdisciplinary approaches using cutting edge technologies to understand key Human Health processes involved in intracellular growth, egress and red cell invasion by malaria Malaria parasites. Another project initiated to focus study on the molecular epidemiology of A recombinant malaria vaccine candidate malaria in endemic regions of Central India against Plasmodium falciparum, JAIVAC-1, in collaboration with the Regional Medical which is composed of two recombinant Research Centre for Tribals (RMRCT), protein antigens, PfMSP1 and PfF2, 19 Jabalpur, Madhya Pradesh has been formulated with the adjuvant Montanide ISA initiated. This project aims to characterize 720 was tested in a Phase I clinical trial. the invasive properties of P. falciparum This is the first novel recombinant vaccine isolates from the field, and to understand developed indigenously and tested for the naturally acquired immune responses first-time-in human clinical trial in India. against blood stage parasite antigens and JAIVAC-1 was found to be safe and elicited their role in protection against malaria. robust antibody responses against PfF2 but poor immune responses against PfMSP119. A next generation vaccine candidate Immunology JAIVAC-2, which contains PfF2 and

PfMSP119-PfMSP311, has been developed to Several host-factors have been identified that overcome with the problem of poor are required by the Mycobacterium for its

287 International Centre for Genetic Engineering Annual Report : 2011-12 and Biotechnology survival within host through genome-wide Virology siRNA approach. Subsequently, complete metabolome, lipidome, proteome and The Hepatitis E virus studies attempted to transcriptome profile of macrophage cells identify the cellular receptor for the virus, infected with Mtb are being generated to and to characterize patient plasma and urine represent finest details of cellular responses proteomes and metabolomes towards the upon infection. A novel protein-kinase identification of disease biomarkers and a centric network regulating overall cellular comprehensive understanding of pathogenesis. The HIV research programme responses were identified that are now being has dealt mainly with understanding the investigated for their efficacy as potential role of small non-coding RNAs or drug targets against tuberculosis. The microRNAs in disease pathogenesis. These group has also discovered a novel role studies led to the identification of a viral of mesenchymal stem cells in suppressor of RNA interference that regulating immune responses against Mtb functions through a novel mechanism not infection. observed earlier in animal viruses. Gene- expression, microRNA and metabolite Under the second phase of ‘Centre of signatures have also been characterized in Excellence Program on TB Research’, it is HIV/AIDS patients to serve as biomarkers planned to develop novel intervention of disease progression and therapy failure. strategies for tuberculosis. Under the project A novel mechanism mediated by the funded by a Bill and Melinda Gates influenza virus nucleocapsid protein was Foundation (BMGF: Phase-I) on electronic uncovered that restricts innate immunity in nose for pulmonary tuberculosis disease infected cells. Multiplex detection strategies identification using breath of TB patients were used to understand the ecology of was successfully completed. Initial findings respiratory viruses in patients and evidence showed promising results which are under was found for a newly discovered virus in these specimens. further validation. Based on the Phase I research, further funding (Phase-II) was Structural and Computational Biology received from BMGF and Canadian Grand Challenge for validating breath based The group has recently performed structure biomarkers for TB in a multicentric determination of dehydroascorbate reductase longitudinal study. from Pennisetum glaucum, which has guided

288 Annual Report : 2011-12 InternationalBiotechnology Centre Information for Genetic System Engineering Network and Biotechnology to decipher the functional role of this Recombinant Gene Products protein in rescuing plant cells from oxidative stresses. In addition, extensive Novel recombinant designer proteins have NMR-based metabolomics efforts on human been developed as an inexpensive, highly biofluids are on-going in an effort to sensitive and a specific diagnostic discover biomarkers of human disease. The intermediates for viral infections, like HCV, group collaborates with malaria group for HIV and Dengue virus. The availability of validation of prediction methods for these high quality diagnostic intermediates Plasmodium protein annotations. Several new to manufacturers of diagnostic kits has prediction algorithms have been developed reduced production costs significantly and in the past year for enhancing annotation of these kits are being manufactured in India various genomic databases. A new initiative and being used in several Asian and African aimed at inhibitor discovery against diseases countries. Based on the diagnostic such as malaria and tuberculosis has been intermediates, a test has been undertaken. The strategy is to identify small commercialized for the detection of dengue molecular inhibitors with anti-pathogen NS1 antigen from all 4 dengue serotypes. properties and to develop them further. This In consultation with the Indo-US Vaccine will be based on high throughput screening Action Program, the group has created technologies and a wider spectrum of drug- DENV-2 envelope-based virus-like particles like libraries. (VLPs) and are currently under evaluation.

Fig: 12.1: Dengue DAY 1 Test Kit

289 International Centre for Genetic Engineering Annual Report : 2011-12 and Biotechnology

Studies have been initiated towards finding characterized for their potential use as the potent binders and inhibitors of some candidate genes for genetic transformation selected proteins of DENV-2. using tobacco as the model system. Stress- induced beta-carbonic anhydrase from C4 Synthetic Biology and Biofuels plant (Pennisetum glaucum) has been characterized and a new genome walking An E. coli strain was engineered through method to find out transgene integration manipulation of endogenous pathway that loci in transgenic genome has been could take-up all the C5 and C6 sugars developed. present in the lignocellulosic biomass and converts them into ethanol at a near The role of RAD54 in-vitro geminivirus DNA theoretical yield. Efforts have been initiated replication with yeast extract has been at ICGEB to establish a ‘DBT-ICGEB Centre established. The tomato transgenic plants for Advanced Bioenergy Research’. The expressing the artificial microRNA that proposed collaborative centre shall be target the conserved region of the pre-coat expanding its activity towards genomic, protein of a geminivirus, namely ToLCV metagenomic, synthetic and systems biology have been developed. Few host proteins areas for addressing some of the key issues such as GRF1, MCM2, MCM3 having of biofuel development such as finding interaction with Rep protein of MYMIV have efficient cellulolytic enzymes, developing been identified. Arabidopsis GRF1 was biocatalysts for C5/C6 fermentation, demonstrated to modulate the replication generating advance biofuel molecules, and efficiency of geminiviral DNA. More than developing robust algal strain for biodiesel 200 known and ~1500 novel rice miRNAs production. have been identified.

Agricultural Biotechnology Plant Transformation

Plant Molecular Biology Efforts have been continued to express various therapeutically and commercially Several rice transgenic lines for enhanced important biomolecules in tobacco tolerance to salinity and drought stress chloroplast. Under the Indo-Finland conditions have been generated and collaborative project supported by the DBT, validated. Novel stress responsive genes PTG group in collaboration with a Group from plants and fungus were cloned and at VTT, Finland has produced D1

290 Annual Report : 2011-12 InternationalBiotechnology Centre Information for Genetic System Engineering Network and Biotechnology antibodies, (ScFv and Fab) in plants at a and two pro-region peptides that concentration of ~2-4% of the total soluble specifically kill neonate larvae of Helicoverpa protein. Similar approach was used to armigera have been identified. By subtractive express ten cellulolytic enzymes in tobacco micro RNA library screening, the group has chloroplasts in collaboration with the identified a specific miroRNA that regulates University of Pavia, Italy. High throughput expression of chitinase in developing larvae. transcriptomic and proteomic analyses were The entire genome of Sf21 has been used to identify genes involved specifically sequenced and annotated for the in the development of cotton fiber under identification of new RNAi factors. The data NAIP funded project. This study showed is being scanned for RNAi pathway that drought has profound effect on fibre components and microRNA identification. elongation by down-regulating important In addition, the group has profiled genes involved in cell wall loosening and microRNA’s in malaria parasite transmitting expansion process. vector, Anopheles stephensi at various stages of maturation of Plasmodium. Several unique Insect Resistance strains of bacteria were identified from the gut of larvae and adult mosquitoes, Investigations were continued for exploring which are being modified to be employed insect genomes for identification of proteins as delivery agent for desired genes in the that could be useful as insecticidal agents gut.

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291

Chapter 13

PROMOTION OF BIOTECHNOLOGY IN THE NORTH EASTERN STATES OF INDIA

The North East Region (NER) of India is biotechnology programmes in the North abundant with rich biodiversity, mineral, Eastern States of India as part of DBT’s water and forest resources and has been commitment towards the promotion of identified as one of the world’s biodiversity biotechnology activities in the North hotspots in terms of spread across diverse Eastern Region. A separate building ecosystems with rich genetic resources. It measuring 2000 sq. ft. area has been hired also offers rich biodiversity of floral and for the NER-BPMC office. The NER-BPMC office is now functional with the faunal elements and provides ample appointment of consultants and project opportunities for furthering economic managers. The NER-BPMC is working in development of the region. In the region close cooperation with DBT and other agriculture contributes to ~ 30% of the Net Government Ministries/ Department/ State Domestic Product (NSDP) and ~ 75% Agencies at the Central and State of the region’s population depends on the level alongwith universities and research same for employment. Hence, agriculture institutions for development and and allied sectors were kept as priority areas implementation of various programmes. for biotechnology based development in the region. In view of these, the Department of NER-BPMC has initiated a number of Biotechnology has earmarked 10% of its activities towards biotech based total budget amounting to Rs. 140 crores development of the NER in the following for the year 2011-12 to promote thrust areas: biotechnology activities in the North Eastern Region of India. Integrated Technology/Product Development In the year 2009-10, DBT has set up a North Eastern Region-Biotechnology Programme Three projects aimed towards Integrated Management Cell (NER-BPMC) through Technology/Product Development have Biotech Consortium India Limited (BCIL) been initiated/ implemented during the for coordination and monitoring of year.

293 Promotion of Biotechnology in the Annual Report : 2011-12 North Eastern States of India

Twinning Programme of scientists working in NER. In the year 2011-12, a total of 230 proposals were The Twinning R&D program for NER was received, out of which 117 proposals have initiated in the year 2009-2010 towards been approved for funding. developing core competence and core capacity in different areas of biotechnology A new project tilted ‘Biotechnology led viz. Health Science, Agricultural Science, organic farming in the NER’ focusing large Veterinary Science, Pharmaceutical Science, scale demonstrations of use of bioinputs Biomedical Engineering, Bioinformatics, for organic farming of key high value crops Food and Nutrition, Health Care including (HVCs) of NER has been launched in alternative medicine, Nanotechnology and September, 2010 for a period 3 years. Three Environmental Biotechnology, through joint institutions, namely: ICAR-RC, Umiam, venture, between two or more institutes, Meghalaya, 14 Krishi Vigyan Kendra’s where one of the institute is from North (KVKs) of NE zone of ICAR and IBSD, East India. This collaboration is expected Manipur of DBT are major implementing to play a crucial role in upgrading the skills partners of the project. Till December, 2011,

Fig. 13.1: Twinning R&D program for NER

294 Annual Report : 2011-12 Promotion of Biotechnology in the North Eastern States of India

Fig.13.2: Cultivation of Organic Chilli (Bhutjholakia) in Golaghat project activities like training trainers, (b) AAU, Khanapara (Veterinary Campus farmers and field demonstrations on and (c) NEIST, Jorhat (CSIR Institute) with identified crops established. Brief project the following objective: (a) Taxonomical achievements are: studies of four MAP Species, (b) Isolation of bioactive phytochemical ingredients of • 1400 farmers trained on organic farming medicinal value, (c) Evaluation of technology using bio inputs pharmacological activity of bioactive plant (biopesticides, biofertilizers, botanicals) extracts /fractions, (d) Assessment of for 9 horticultural crops. isolated drugs for possible adverse effects • Field demonstrations with organic on metabolic system, and (e) Development package in 158 ha already established of Good Agricultural Practices (GAP), large First year results from completed field scale production of planting material & demonstrations are encouraging and PHT. profitable. Capacity Building Biodiversity Conservation & Utilization Key initiatives were taken towards During the year, DBT has initiated a research development/upgradation of infrastructure network titled “ Biotech Intervention on in Medical colleges, establishment of Selected Medicinal & Aromatic Plants (MAP) Biotech Hubs, North Eastern Bioinformatics of NER for their effective utilization” on Network (NEBINet), DBT’s e-Library four medicinal & aromatic plants (MAP), Consortia (NER-DeLCON), online human launched in October, 2011 involving three resource repository of Biotechnology and partner institutions (a) AAU, Jorhat (Agric.) Bioinformatics Resources of North East India

295 Promotion of Biotechnology in the Annual Report : 2011-12 North Eastern States of India

(BABRONE) and development of Digital North Eastern Region of India offering Database of Bioresource of NE India etc. undergraduate and/or postgraduate courses in any branch of Biology/Life Science/ Development/upgradation of infrastructure Biotechnology/Environmental Science/ in Medical colleges in North Eastern States Chemistry /Physics/ Computer Science / of India Biomedical Sciences/ Agri/ Veterinary Sciences for 3 years to establish/upgrade a The DBT program on Development/Up- basic biotechnology lab, develop a gradation of Infrastructure in Medical bioinformatics center, avail biotechnology e- Colleges in the NER was started in the year journal, support for organizing training for 2009. The program is now operational in 12 teachers etc. 6 State level and 34 institutional medical colleges/ institutions in four states level biotech hubs were established and 52 of the Region, namely Assam, Nagaland, additional institutional level biotech hubs Tripura and Manipur. Labs of 21 Principal sanctioned at various colleges/universities/ Investigators have been renovated/upgraded institutes during this year. These for carrying out quality research on various facilities will impart research insight among health problems prevalent in the the budding science students at region using modern biotechnology tools their formative stage of science education and technologies. Various scientific (UG/PG level) and research career (PhD equipments including 27 high cost level). equipments such as flow cytometer, Real- Time PCR machine, Hi-speed centrifuges, - North Eastern Bioinformatics Network 80º C freezers etc. have been procured and (NEBINet) installed. Twenty seven bioinformatics centers Establishment of Biotech Hubs for the established in all the 8 states of the NER North Eastern States were networked as the North Eastern Bioinformatics Network (NEBINet). These A Biotech Hub Scheme was initiated during Bioinformatics centres are provided with the year 2010-11 and continuing during 2011- latest IT equipment to support the research 12 with the broad purpose of promotion of activities of the host institutions in NER. education and research in Biology/Life The network is quite popular in outreach Science/Biotechnology. Institutes/Colleges/ of various programmes to NER in addition Universities of higher education of the to information collection and dissemination.

296 Annual Report : 2011-12 Promotion of Biotechnology in the North Eastern States of India

DBT’s e-Library Consortia (NER- A network programme with 8 PIs from 7 DeLCON) different institutes of NER on development of a digital database of bio- DBT’s e-Library Consortia for North Eastern resources of North East India has been Region (NER-DeLCON) was established in sanctioned by DST. The Programme is the year 2010 through which more than 900 aimed at digitizing, structuring, High Impact e-journals were subscribed by developing suitable databases and makes DBT and the facility was offered to 15 it available in the public domain. The selected NER institutions. During the year duration of the project is for 3 years with 2011, 3 new institutions were added from a budget of Rs. 258 lakhs. NER in the consortia. An assessment indicated that scientists, faculty and students of these 18 institutions were using the Human Resource Development subscribed e-journals extensively and also encouraging institutions in the Overseas Associateship for NER neighborhood to utilize this service. scientists DeLCON may be accessed at www.delcon.gov.in. A special programme was developed to BABRONE train early and mid-career Scientists holding permanent positions in NE region During the year, DBT has sanctioned a conducting research to generate human project on creation of an online human resource in cutting edge areas of resource repository of Biotechnology and biotechnology. The Overseas Fellowship Bioinformatics resources of North East India has been awarded for both short (3 & 6 (BABRONE). This online repository will be months) and long (1 year) term period. first of its kind that will provide During the last year 21 scientists availed comprehensive information regarding associateship in established institutions in biotechnology and bioinformatics resources different foreign countries including USA, of NE India preferably via open-source software. Japan, Canada, UK, Germany and France. During this year Seven Overseas Network Program on Development of Fellowship has been awarded to for long Digital Database of Bioresource of NER term training while 27 were approved for India short term period.

297 Promotion of Biotechnology in the Annual Report : 2011-12 North Eastern States of India

Award of Biotechnology National them in establishment of a successful Associateship to Scientists working in enterprise in NER. North Eastern States A training programme on entrepreneurship National Associateship Programme for development sanctioned to The Energy & training both for short term and long term Resources Institute (TERI), Guwahati for has been initiated for the award of production of superior quality planting Biotechnology National Associateship for material using in vitro technology in conducting research or training in National Northeast India. This programme aimed at Institutions/research laboratories in different enhancing the technical capability of the areas of biotechnology such as (i) entrepreneurs and scientists researching/ agriculture, food and feed biotechnology; engaged in mass production of tissue (ii) animal biotechnology; (iii) aquaculture cultured plants and appraising them about and marine biotechnology; (iv) food and the current development in this field. nutrition; (v) environmental biotechnology (vi) industrial biotechnology: materials Centres of Excellence biotechnology, reaction and process design; (vii) medical biotechnology; (viii) nano- biotechnology and bioengineering; (ix) For strengthening agro-biotechnology bioinformatics and IT-enabled research in NER, DBT partnered with Assam biotechnology; (x) intellectual property and Agricultural University, Jorhat to establish patent law. a ‘DBT-AAU centre for Agriculture Biotechnology’ at AAU, Jorhat. The major Entrepreneurship Development in NER focus of the centre will be on: (a) Basic research-Gene technology, molecular DBT had entrusted a project to Biotech breeding and microbial gene prospecting, Consortium India Limited (BCIL) to organize (b) HRD component with strong Ph.D. a series of Entrepreneurship Development programme, and (c) Extending technology Programmes (EDPs) in NER for handholding benefits through enhanced production of bio the budding entrepreneurs and assisting inputs etc.

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298 Chapter 14

NEW LEGISLATIONS AND REGULATIONS

DNA Profiling Bill Regional Centre for Biotechnology (RCB) Bill Human DNA Profiling Bill has been formulated by the Department in Regional Centre for Biotechnology would consultation with the Centre for DNA be an international nodal institution for Fingerprinting and Diagnostics, Hyderabad. biotechnological sciences at the interface of The objectives of this Bill are to regulate multiple disciplines and would be an the use of DNA analysis of body substance autonomous body under the statute of profiles; making provision for Parliament as an institution of international establishment of DNA Profiling Board to importance for biotechnological Education, lay down standards for laboratories, Training and Research. Hon’ble Minister for collection of body substances; to establish Science & Technology and Earth Sciences a National and /or State DNA Data Banks introduced a Bill (Item No. 27) during the to create policies for use and winter session (9th Session of XV Lok Sabha) access to information from data bank etc. on 20th December, 2011 to facilitate the and for matters connected therewith or establishment of the institution and Training incidental thereto. The Draft Bill was and Education as Category-II institution subsequently circulated to the concerned under the auspices of UNESCO to undertake Ministries and Departments of the Central research in the field of biotechnology and Government to obtain their comments. The to provide for matters connected therewith draft Bill has since been revised, or incidentally thereto. wherever necessary, according to the comments received. Draft Bill has been Biotechnology Regulatory sent to the Chief Secretaries of all the States Authority of India (BRAI) Bill, for information and feedback. The 2010 document is being further revised based on the discussion held with the experts to BRAI will be an independent, autonomous, bring more clarity on various issues. statutory agency and will be established

299 New Legislations and Regulations Annual Report : 2011-12

through the act of parliament by the responsible for regulating the research, Government of India to safeguard the health transport, import, manufacture and use of and safety of the people of India and to organisms and products in health care, protect the environment by identifying risks agriculture, veterinary and environment. The posed by, or as a result of, modern BRAI bill after cabinet approval has been biotechnology and managing those risks tabled in Lok Sabha for introduction. A through regulating the safe development detailed establishment plan has been and deployment of biotechnology products prepared with requirements of human and processes. The Authority will be resource, infrastructure and managerial aspects.

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300 Chapter 15

ADMINISTRATION AND FINANCE

being taken to tackle the issue- first by Administration getting some additional built-up office space and second by getting a piece of land Administration is responsible to provide a to make its own building. good and ambient working atmosphere for the in-house scientists, officers and staff. Logistic supports were given for organising Establishment various Task Force & Expert Committee meetings successfully. Modern office Establishment Division has been entrusted equipments like laptops, computers, with the functions relating to mainly the multimedia projectors, photocopiers, etc. service matters of in-house scientists, officers were made available within the Department and staff of the Department. These matters to maximise the work output. Being a include their recruitment & promotion to scientific department, a large number of various posts, Flexible Complementing meetings, interactions and quick referral Scheme (FCS), grant of financial up- with technical experts, specialists, gradation under ACP/MACP Scheme, academicians and scholars from far reaching reimbursement of medical claims, grant of places and across the world are held. various advances etc. During the period Therefore, to obviate unnecessary travelling under report 1 post of Scientist ‘C’, 2 posts and to minimise expenditure on this of Junior Analyst and 5 posts of Multi account, an effective Video Conferencing Tasking Staff were filled up on direct System has been made operational in the Department. The System is widely used in recruitment basis. Under Flexible the Department for such purpose. Complementing Scheme (FCS), One Scientist of the department was promoted i.e. one Presently, the Department does not have its from Scientist ‘E’ to Scientist ‘F’ and seven own building or campus and is facing cases of grant of promotion to their next shortage of office space. This has restricted higher grade under FCS were also the long felt expansion plan of the processed. 12 officials were granted financial Department. Two pronged strategies are up-gradation under the Modified Assured

301 Administration and Finance Annual Report : 2011-12

Career Progression (MACP) scheme. The Parliamentary matters officers and staff were deputed for various No meeting had been held during April – training programme conducted by the December, 2011. institute of Secretariat Training & Management, National Productivity Council Grievance Redressal and other such institutes to enhance their skills in relevant fields. Department has established an effective grievance redressal mechanism to deal with The category-wise position of posts the public as well as the staff grievance sanctioned and filled as on 31.12.2011 is as petitions. All public grievances received under:- during the period of April-December, 2011,

Category of posts Posts sanctioned Posts filled

Group ‘A’ 76+8 Plan 66+2 Plan

Group ‘B’ 89 66

Group ‘C’ 87+1 Plan 67+1 Plan

Total 252+ 9 Plan 199

Representation of SC/ST/OBC/PH: The number of SC/ST/OBC/PH employees in various posts as on 31.12.2011 is as under:

Groups/ Group ‘A’ Group ‘B” Group ‘C’ Grand Total

Sectioned strength/ 76+8 Plan 89 87+1 Plan 252+9 Plan Total Filled 66+2 Plan 66 67+1 Plan 199+3 Plan

Scheduled Castes 02 10 21 33

Scheduled Tribes 03 03 09 15

Other Backward Classes -060410

Physically Handicapped 02 03 - 05

302 Annual Report : 2011-12Biotechnology Information Administration System and Network Finance

were disposed of in a time bound manner. quarter and suggests corrective measures The department regularly updated progress, for promoting use of Hindi. During the year, disposal and pendency of public grievances all documents were issued in bilingual form on the website of Department of Reforms & and the letters received in Hindi were Public Grievances. replied to in Hindi only under Section 3(3) of the Official Languages Act, 1963. In order Vigilance Unit to strengthen the monitoring system of progressive use of Hindi, the officers who A Vigilance Cell is functioning in the sign the papers have been made the check- Department to handle vigilance and points. Under Rule 8(4) of the Official complaint cases expeditiously. During the Language Rules, 1976, Establishment, period of April – December, 2011, only 3 Administration, PPVC, Cash sections and vigilance case was registered. However, Library in the Department have been complaints received from various sources notified to do their 100% work in Hindi. were processed timely and the Central Hindi fortnight was organized in the Vigilance Commission was kept apprised Department during 1 - 15th September, 2011, of the progress and final outcome of these in which 8 different competitive events complaints. In pursuance of the instructions namely Essay, Hindi-English Translation, of the Central Vigilance Commission, a Debate, Scientific Articles, Noting & ‘Vigilance Awareness Week’ was observed Drafting, Hindi Quiz, Hindi Typing and in the Department from 3rd to 7th November, Antakshari were held to promote use of 2011. Hindi in official work. Ten officers and twenty eight other employees were given Progressive Use of Hindi in the cash prizes in a prize distribution ceremony Department organized under the chairmanship of Secretary (DBT) on 19 October, 2011 in which Hindi division ensures progressive use of the first prize of Rs.2000/-, second prize of Hindi and implementation of Government Rs.1500/-, third prize of Rs.1200/- and 5 policy on Official Language in the consolation prizes of Rs.1000/- were given. Department. An Official Language Secretary, DBT gave away the prizes and Implementation Committee, constituted through his speech motivated the officers under the chairmanship of the Joint and staff to work in hindi. With a view to Secretary (Admn.) in the Department, encourage writing original books on reviews progressive use of Hindi in every biotechnology related subjects in Hindi, the

303 Administration and Finance Annual Report : 2011-12

Department has been carrying out an award distinguished themselves with excellent scheme namely “Dr. Jagdish Chandra Bose performance. Dr. Gulshan Wadhwa, Ms. Hindi Granth Lekhan Puraskar Yojna” since Alka Mankad, Ms. Rajani Kushwaha and 2002. Under this scheme, one second prize Ms. Mahak Garg represented DBT in Inter- for Rs. 50,000/-, one third prize for Rs. Ministry Badminton Tournament 2011-12 25,000/- and two consolation prizes for Rs. held at AIIMS, Gymkhana, New Delhi and 10,000/- each were awarded for the selected and Ms. Alka Mankad won Silver Medal in books for the year 2009. During the year, Women Doubles (Veteran). Ms. Rajani 103 officers/employees were imparted Kushwaha, Mr. Anurag Mishra, Ms. Mahak training in three Hindi workshops/Scientific Garg and Mr. D. Rajshekhar represented Symposia organized in the Department DBT in Inter-Ministry Chess Tournament during the year. All the Sections/Divisions 2011-12 held at Nirman Bhawan, New Delhi, of the Department were inspected by the for the first time. The officials of Department officials of Hindi section during the year in of Biotechnology are also participated in order to ensure the progressive use of Hindi the Inter-Ministry Music & Dance and Short as well as to facilitate officials of the various Play Competition, 2011-12 in the events of Divisions for making them more efficient in Folk Dance – Solo and Folk Dance-group, Hindi working. In order to review the Western Dance and Folk Music categories. implementation of official language hindi in the department’s autonomous bodies/ public sector undertakings, an inspection has already been carried out in the Regional Centre of Biotechnology, Thiruvananthapuram (Kerala) and inspection of other four offices such as NII, New Delhi; NIPGR, New Delhi; NBRC, Gurgaon and BIBCOL, Bulandshahar are scheduled to be carried out by the end of Fig.15.1 the year of report. 99th Indian Science Congress Sports and Cultural Activities Dr. Manmohan Singh, Hon’ble Prime A number of DBT officials participated in Minister inaugurated the 99th Indian Science the Inter-ministry Tournaments 2011-12 and Congress held at KIIT, Bhuvaneshwar on

304 Annual Report : 2011-12Biotechnology Information Administration System and Network Finance

programmes and new schemes. Noble Laureates visited the DBT exhibition stall, enthusiastically interacted on various programmes of DBT. Dr. Gulshan Wadhwa, Dr. Peyush Goyal, Shri Anadi Sharma, Ranjit Singh, Shri Pramod Kumar and Shri Narendra Kumar from the Department coordinated the exhibition as two teams. Statistics in Bioinformatics – an exclusive session was held in the Science Congress, Fig.15.2 which was chaired by Dr. T. Madhan Mohan, Adviser, DBT. 3rd – 7th January, 2012. The Focal theme for the Science Congress was “Science and Finance Technology for Inclusive Growth of women”. The Exhibition on :Pride of India” The Department of Biotechnology was was inaugurated by Shri Vilas Rao allocated an amount of Rs.1426.92 Crores Deshmukh, Hon’ble Minister for Science and (Rs. 1400.00 Crores (Plan) and Rs.26.92 Technology and Earth Sciences. Crores (Non-Plan) for the year 2011-12. This was revised to Rs.1376.70 Crores (Rs. 1350.00 More than 12000 registered delegates from Crores (Plan) and Rs.26.70 Crores (Non- India and abroad, including five Nobel Plan). The financial statement showing the Laureates have participated in the Science details of actual expenditure during 2010- Congress. The Department took part in the 11, B.E. and R.E. 2011-12 in respect of exhibition during the science congress with various programmes/schemes is enclosed illustration of DBT’s major activities, in Annexure-V.

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305

Annexure-I

ANNEXURES

The short term training programmes conducted during the year

S. Title of the Organizers Duration No. of No. Programmes Participants

1. Molecular Biology Dr. Prakash M. Halami, 4th -19th March, 15 Techniques Scientist E1, Food 2011 in Microbiology Microbiology Department, Central Food Technology Research Institute (CFTRI), Mysore, Karnataka-570020

2. Agroindustrial Dr. S. Rathinavel Associate 23rd May to 15 th applications of ProfessorPG and Research 11 June,2011 plant tissue Department of Botany, culture, Saraswathi Narayanan College Agrobacterium (Autonomous) Madurai- 625022 (T.N) mediated gene transfer and PCR techniques

3. Cynobacterial Dr. L. Uma, Director, 27th Feb to 9th 15 Sequencing National Facility for Marine March,2012 Techniques Cynobacteria, Department of Marine Biotechnology, Bharathidasan University, Tiruchirappalli-620024 (T.N)

4. Methods in Dr. J. Joel Gnanadoss, 1st - 21st Feb, 15 Biotechnology, Assistant Professor, 2012 molecular biology Department of Plant Biology and bioinformatics and BiotechnologyLoyola College (Autonomous)Chennai-600034 (T.N)

307 Annexures Annual Report : 2011-12

Annexure-II Number of Biotechnology students trained by companies under Biotech Industrial Training Program (BITP) during 2011

S. Name of com[pany No. of students No. trained

1 Abexome Biosciences Pvt Ltd 5 2 Advanta India Limited 1 3 Advinus Therapeutics Limited 1 4 AG Bioteck Laboratories (I) Ltd. 3 5 Agri Biotech Foundation 3 6 Aptus Biosciences Pvt Ltd 3 7 Ara Healthcare Pvt Ltd 15 8 Arbro Pharmaceuticals Ltd 2 9 Aristogene Biosciences Pvt Ltd 4 10 Ashmar Technologies and Research Pvt Ltd 2 11 Asian Institute of Gastroenterology 4 12 AstraZeneca Pharma India Ltd 3 13 Atash Seeds Pvt. Ltd 1 14 Aumgene Biosciences Pvt. Ltd. 3 15 Aurigene Discovery Technologies Limited. 1 16 Aurobindo Pharma Ltd 2 17 Auroprobe Laboratories 100 18 Avesthagen Limited 3 19 Azyme Biosciences Pvt Ltd. 1 20 Bangalore Biotech Labs Pvt. Ltd. 45 21 Barwale Foundation 8 22 Beckman Coulter India Pvt Ltd 1 23 Bejo Sheetal Seeds Pvt Ltd 4 24 Best Biotek Research labs (P) Ltd. 2 25 Bharat Immunologicals and Biologicals Corporation Ltd 2 26 Bharat Serums and Vaccines Ltd 2

308 Annual Report : 2011-12 Biotechnology Information SystemAnnexures Network

S. Name of com[pany No. of students No. trained 27 Bhat Bio Tech India P Ltd 6 28 Biocon Ltd. 10 29 Biological E Ltd 10 30 BioMed Informatics 10 31 Bioserve Biotechnologies (India) Pvt Ltd. 7 32 Bio-tech Laboratory, Neri, Unit of Ankur Seeds Pvt. Ltd. 6 33 Cavinkare Pvt Ltd 1 34 Century Pharmaceuticals Ltd 2 35 Clairvolex Knowledge Processes Pvt. Ltd. 1 36 Clonz Biotech Private Ltd 1 37 Codon Biotech Private Limited 6 38 CPB India P Ltd 1 39 Dabur Research Foundation 9 40 Dr.Surapaneni’s Genomic Solutions Pvt Ltd 4 41 Embio Limited 2 42 Enzene Biosciences Private Limited 4 43 Epitome Consulting and Information Technology Pvt. Ltd. 1 44 Gangagen Biotechnologies P Ltd 1 45 Gennova Biopharmaceuticals Limited 8 46 Geno Biosciences Pvt Ltd 1 47 Genotypic Technology Pvt Ltd 3 48 GenPro Biotech 4 49 Global Transgenes Ltd 1 50 GVK BioSciences Pvt Ltd 2 51 Hash BioTech Labs Pvt Ltd 7 52 Health Line Pvt Ltd 1 53 Healthcare Global Enterprises Ltd 1 54 Imgenex India Pvt Ltd 9 55 Indian Immunologicals Ltd 6 56 Indo-American Hybrid Seeds (India) Pvt. Ltd. 11

309 Annexures Annual Report : 2011-12

S. Name of com[pany No. of students No. trained

57 Indus Seeds 6 58 Institute of Molecular Medicine 1 59 Intas Biopharmaceuticals 10 60 Jai Biotech Industries 1 61 Jai Research Foundation 1 62 Jay Biotech 4 63 JK Agri Genetics Ltd 6 64 Juan Biotechnology Private Limited 3 65 Jubilant Biosys Limited 11 66 Kaveri Seed Company Ltd 2 67 KEE GAD Biogen Pvt. Ltd. 3 68 Kemwell Pvt Ltd 1 69 Kilpest India Limited 1 70 Krishidhan Research Foundation Limited 1 71 L J International Ltd 1 72 Labland Biotech Pvt Ltd 7 73 Laila Pharmaceuticals Pvt Ltd 3 74 Leadinvent Tech Pvt Ltd 1 75 Lifecare Innovations Pvt Ltd 2 76 Lonza India Pvt Ltd 2 77 Maharashtra Hybrid Seeds Co. Ltd. 1 78 Maharashtra State Seeds Corporation Limited 5 79 Manipal Acunova Ltd. 2 80 Mediclone Biotech Pvt. Ltd 10 81 Metaome Science Informatics (P) Ltd 5 82 Micro Labs Ltd 1 83 MITCON Consultancy Services Ltd. 4 84 Monsanto Holding Private Limited 1 85 Myko Tech Private Limited 1 86 Nandan Biomatrix Limited 2

310 Annual Report : 2011-12 Biotechnology Information SystemAnnexures Network

S. Name of com[pany No. of students No. trained

87 Natural Remedies Pvt Ltd 8 88 Nectar lifesciences ltd 2 89 Nirmal Seeds India Pvt Ltd 4 90 Ocimum Biosolutions 3 91 OncQuest Laboratories Ltd 6 92 Orchid Chemicals & Pharmaceuticals Ltd 8 93 Oriental Aquamarine Biotech India Private Limited 3 94 Panacea Biotec Ltd 5 95 Pelican Biotech and Chemical Labs Pvt Ltd 3 96 Perfint Healthcare Pvt Ltd 3 97 Piramal Diagnostic Services P Ltd 1 98 Polyclone Bioservices Pvt Ltd 1 99 Praj Industries Limited 4 100 Pranav Agro Industries ltd 1 101 Premas Biotech Pvt. Ltd 2 102 Probiosys 3 103 Prosetta Bioconformatics Pvt Ltd 1 104 Radiant Research Services Pvt. Ltd. 3 105 Rashmi Pharma Pvt. Ltd. 1 106 Rishi Herbal Technologies Pvt Ltd 4 107 Roche Diagnostics India Pvt Ltd 2 108 S&S Agro Biotech Pvt Ltd 4 109 S.P.Y Agro Industries Ltd. 2 110 S4BIO 7 111 Sai Lara Biotechnologies 4 112 Sandor Proteomics Pvt Ltd 6 113 Sangenomics Research Labs Pvt Ltd 2 114 Serum Institute of India 1 115 Shantha Biotechnics ltd 4 116 Shodhaka Life Sciences Pvt. Ltd 5

311 Annexures Annual Report : 2011-12

S. Name of com[pany No. of students No. trained

117 Shri Meera Labs Pvt Ltd 5 118 Simbiosys Biowares India Pvt Ltd 1 119 Span Diagnostics Limited 3 120 SPC Biotech Private Limited 4 121 Sri Biotech Laboratories India Limited 3 122 Sri Raghavendra Biotechnologies P Ltd 9 123 Subhash Fertilizer Private Limited 2 124 Subhasree Biotech 4 125 Sugen Life Sciences Pvt Ltd 8 126 Sun Agrigenetics P. Ltd. 5 127 Super Religare Laboratories Ltd 2 128 Surya Pharmaceutical 1 129 T Stanes and Company Ltd 9 130 Tapadia Diagnostic Centre 1 131 Tata International Ltd 1 132 Tectona Biotech Resource Centre 9 133 Tex Biosciences P Ltd 1 134 The Gene Tech 2 135 Tropilite Foods Pvt Ltd 2 136 Tulasi Seeds Pvt. Ltd. 1 137 UB Nizam Breweries Pvt. Ltd. 1 138 United Breweries Limited 2 139 Vasantdada Sugar Institute (VSI) 1 140 Vimta Labs Ltd 3 141 Virchow Biotech Pvt. Ltd. 1 142 Vittal Mallya Scientific Research foundation 1 143 Vivo Biotech Ltd 2 144 Wockhardt Limited 4 145 Xpression Biotek Pvt Ltd 3 146 Zenotech Laboratories Ltd 2

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Annexure-III Products /Processes under development through BIPP support

S. Company/Collaborator(s) Product/Process description No. Name

Health Care/Drugs/Vaccines 1. Torrent Pharmaceuticals Drug for Diabetes associated Heart Failure 1. Limited, Gandhinagar

2. ARA Healthcare Limited, Anti- TNF-alpha Antibody scFv for treatment of Gurgaon Inflammatory Diseases 2. 3. TCG Life Sciences Limited, Process for Asymmetric Synthesis of Kolkata Hexahydrobenzophenanthrenes, Dopamine D1 Agonists

4. Bharat Serums and Vaccines Technology development for implant based Limited, Mumbai sustained release formulations incorporating therapeutic peptides/ recombinant proteins

5. (i) Amrita Therapeutics Limited, Ahmedabad (ii) National Institute of Identification and Development of Promiscuous Immunology, New Delhi Anticancer Compounds from Microorganisms (iii) B.V. Patel PERD Centre, Ahmedabad

6. Wockhardt Limited, Development of animal component free Aurangabad biosimilar recombinant protein therapeutics using mammalian platform technology

7. Life Care Innovations Pvt. Production of poly (lactide-co-glycolide) Ltd., Gurgaon nanoparticles (PLG-NP )and poly (lactide- co-glycolide) nanoparticles encapsulating antitubercular drugs (rifampicin, isoniazid and pyrazinamide- PLG-NP-ATDs) in GMP facilities

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S. Company/Collaborator(s) Product/Process description No. Name

8. Virchow Biotech Private Mucosal Vaccine For HPV Ltd., Hyderabad

9. Gennova Biopharmaceu-ticals Recombinant Human Papillomavirus vaccine Limited, Pune

10. Gennova Biopharmaceu-ticals Bio-similar interferon beta 1a: process Limited, Pune development

11. (i) Serum Institute of India Limited, Pune (ii) Indian Institute of Immunogens and monoclonal antibodies Science, Bangalore against pandemic H1N1 (iii) National Institute of Immunology, New Delhi

12. Serum Institute of India Clinical Development of Polysialylated Limited, Pune Erythropoietin

13. Serum Institute of India Ltd., Development of HPV Vaccine Pune

14. (i) RAS Life Sciences, Hyderabad Development of HCV genotype 3a based replicon system (ii) Institute of Liver and Billiary Sciences, New Delhi

15. (i) Sphaera, Manesar (ii) Leadinvent, Delhi Novel combination therapy for treatment of (iii) International Centre for resistant and non responsive cancers Genetic Engineering and Biotechnology , New Delhi

16. Tergene Biotech Pvt. Ltd., Development of an Affordable, Asia specific Secunderabad 15 valent Pneumococcal Ploysaccharide - CRM 197 protein conjugate Vaccine

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S. Company/Collaborator(s) Product/Process description No. Name

17. Rasayani Biologics Pvt. Ltd. Evaluation of Platinum Nano Particles for the Treatment of Hormone Refractory Prostate Cancer

Health Care/Diagnostics

18. Bigtec Private Limited, Point-of-Care detection of infectious disease Bangalore using handheld microPCR

19. Amar Immunodiagnostics Pvt. Immunodiagnostic kits for detection of Ltd., Hyderabad autoimmune diseases

20. Abexome, Bangalore Establishment of vitro phamacological Assay platform for biosimilars

21. Revelations Biotech Pvt. Ltd., Development of low cost rapid quantitative PCR Hyderabad technology for molecular diagnosis

22. Chromous Biotech Pvt. Ltd., Multiplex Fast-PCR based diagnosis and Bangalore prognosis of tuberclulosis

Health Care/Clinical Trial

23. (iv) Bharat Biotech International Limited, Hyderabad (v) Christian Medical College, Vellore Rotavirus Vaccine Candidate 116E (vi) KEM Hospital Research Centre, Pune (vii) Translational Health Science and Technology Institute, New Delhi

24. Torrent Pharmaceuticals Clinical development of TRC150094, a novel Limited, Gandhinagar Diiodothyronine (T2) analogue, for the treatment of cardiovascular (CV) risk factors defined by Metabolic Syndrome (MS).

315 Annexures Annual Report : 2011-12

S. Company/Collaborator(s) Product/Process description No. Name

25. Biocon Limited, Bangalore A Multicenter, Randomized, Double-Blind, Placebo Control Study of IN-105 tablets [oral insulin] in Patients with Type 2 Diabetes Mellitus who have inadequate Glycemic Control on Optimal doses of Extended Release Metformin Tablets.

26. Biocon Limited, Bangalore Open label, randomized, Multicentric studies to Comapre safety and efficacy of Recombinant insulin aspart-biphasic and regular with NovoLog® Mix 70/30 and NovoRapid in T1DM and T2DM patients

27. Panacea Biotec Limited, H1N1 pandemic influenza vaccine New Delhi

28. V-Life Sciences Technology Clinical Investigation of Galnobax for the Pvt. Ltd., Pune treatment of Diabetic foot Ulcers

29. Biological E Limited., A Multicentric, Parallel Randomised (2:1) Open Hyderabad Label Phase III Clinical Study To Evaluate The Immunogenicity And Safety Of BE’s Inactivated JE Vaccine In Healthy e”1 To <3 Year Old Indian Subjects In Comparison With Purified Inactivated JE Vaccine (IXIARO®) Of Intercell – An Non- Inferiority Study

30. Stempeutics Research Pvt. A Randomized, Double Blind, multicentric, Ltd., Bangalore placebo controlled, Phase-II study assessing the safety and efficacy of Intraarterial (Hepatic) Ex- vivo cultured adult allogenic mesenchymal stem cells in patients with liver cirrhosis

31. Crystalin Research Pvt. LTd. Clinical trials of novel anticancer drug cocrystal

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S. Company/Collaborator(s) Product/Process description No. Name

Health Care

32. Perfint Healthcare Pvt. Ltd., Solution for planning, execution and confirmation Chennai of targeted ablation therapy

33. Strand Life Science, Hepatotoxicity prediction platform Bangalore

34. Frontier Lifeline Private Porcine Pulmonary Xenograft as a Conduit in Limited, Chennai Cardiovascular Surgery

35. IMGENEX India Pvt. LTd., Development of High Expression plasmid vectors Bhubaneswar for production of biosimilar herceptin and other recombinant proteins and antibodies

36. Intas Biopharmaceuticals Pvt. Mucosal formulations of Parathyroid hormone Ltd., Ahemedabad (PTH)

37. Incozen Therapeutics Pvt. Discovery and Development of potent, selective Ltd., Hyderabad and novel c-Met kinase inhibitors in cancer

38. Vinvish Technologies Pvt. Design and Development of photo dynamic Ltd., Trivendrum therapy laser system

39. Transasia Biomedical Ltd., To develop novel 3rd Generation HIV (Antibody) Mumbai & 4th generation (HIV Antigen and Antibody) immunoassay forma using flash type chemiluminiscence and magnetic particles as matrix

40. Agada Medical Technologies Percutaneous Aortic Valve Technology

Agriculture

1. Maharashtra Hybrid Seeds Stress tolerant rice Company Limited, Jalna

2. Maharashtra Hybrid Seeds Sucking Insect Pest tolerant rice and cotton Company Limited

317 Annexures Annual Report : 2011-12

S. Company/Collaborator(s) Product/Process description No. Name

3. Metahelix Life Sciences Private Transgenic rice tolerant to rice yellow stem borer Limited, Bangalore

4. Metahelix Life Sciences Private Deregulation Trials Phase I of Transgenic Maize Limited, Bangalore Events Expressing Metahelix Synthetic Cry1C, Cry1Ac and Cry1Ab Genes for Tolerance to Stem and Cob Borers

5. Kaveri Seeds Company Ltd., Development of biotic stress resistant rice through Secunderabad conjunct use of bio-and hybrid technologies

6. JK Agri Genetics Ltd., Development of Bt-rice with two cry genes Hyderabad

7. Advanta India Limited, Drought and multiple diseases & pests tolerant Secunderabad rice through Multi stacking genes

8. (i) Advanta India RNAi and other cuting edge technological Limited, Secunderabad interventions to develop insect-pest diseases & (ii) Indian Agriculture viruses tolerant tomato hybrids for Indian & Research Institute, New International markets Delhi

9. (i) Bejo Sheetal Seeds ‘Herbicide & Stress tolerant’ transgenic Onion Private Limited, Jalna(ii) International Centre for Genetic Engineering and Biotechnology , New Delhi

10. (i) Sri Biotech Labora- Control of Shoot and Fruit Borer Insect Pest tories India Ltd., Hyderabad (Leucinodes orbonalis Guenée) in Brinjal Through (ii) University of Delhi RNA interference South Campus, Delhi

11. Mother Dairy Fruit and To conduct confined field trials and biosafety Vegetable Private Limited, studies on genetically engineered Brassica juncea Noida (Male sterility and restorer lines as pollination control mechanism) for heterosis breeding and yield improvement

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S. Company/Collaborator(s) Product/Process description No. Name

12. Tata Chemicals Limited, Pune Inorganic and polymer nano-composites for micronutrient & pesticide delivery: Boosting crop health and yield.

13. (i) Nirmal Seeds Pvt. Development of nutritionally improved mustard Ltd., Jalgaon(ii) The (Brassica juncea) varieties/hybrids having low Energy and Resources erucic acid and low glucosinolate content using Institute, New Delhi marker assisted selection

14. Ankur Seeds Pvt. Ltd., Third generation RNAi for engineering Tomato Nagpur leaf curl (ToLCV) and tospovirus (GBNV) resistance in tomato

15. Stellence PharmScience Ltd., Development of a bio-efficacious value-added Bangalore novel neem-based biopesticide formulation

16. Bioseed Research India Ltd., Development of rice hybrids with improved Hyderabad drought and salinity stress tolerance

17. Sri Biotech Laboratories India Development of Actinomycetes based Ltd., Hyderabad metabolites as delivery systems for soil health management in Groundnut

18. Abhay Cotex India Pvt. Single step extraction of cottonseed with miscella refining

Energy

1. Avesthagen Limited, Self-glucogenic Pearl Millet for Bio-ethanol Bangalore products

2. Richcore Lifesciences Pvt Ltd., A process for Enhanced Ethanol Yield from Bangalore Molasses Fermentation

3. Nagarjuna Fertilizers and Biological Hydrogen Production Chemical Limited, Hyderabad

319 Annexures Annual Report : 2011-12

S. Company/Collaborator(s) Product/Process description No. Name

4. (i) Bharat Petroleum Butanol production from lignocellulosic biomass Corporation Limited, Greater Noida (ii) The Energy and Resources institute, New Delhi

5. Thermax Limited, Pune Anaerobic Membrane Bioreactor (AnMBR) for Waste to Energy Solutions

6. India Glycols Limited, Setting up a 10 ton Lignocellulosic biomass/day Kashipur processing plant to produce about 3000 Litre ethanol/day

7. SPC Biotech, Hyderabad Bioconversion of Agricultural Waste from Mango kernel, to Polylactic acid a bio-plastic

Capacity Building through Infrastructure Support

1. Span Diagnostics Limited, Establishment of cGMP compliant Bioprocess Surat Facility for large-scale production of Microbial antigens and Monoclonal antibodies

2. Intas Biopharmaceuticals Facility for high end structural and functional Private Limited, Ahmedabad characterization of protein therapeutics and peptides

320 Annual Report : 2011-12 Biotechnology Information SystemAnnexures Network

Annexure-IV Gender Budgeting

As a follow-up of recommendations of the The Gender Budgeting Cell has taken Inter-Departmental Committee set up under necessary action as per the guidelines/ the chairmanship of Secretary (Expenditure) circular of Ministry of Finance for identifying to consider issues regarding Gender specific schemes for which budget needs to Budgeting, the Department has established be earmarked for the benefit of women. a “Gender Budgeting Cell”. The terms of Department’s social Development Reference of the Cell are as follows: Programme on Biotechnology for Women targets the women beneficiaries in terms of • To make an assessment of the benefits both employment and income generation. reaching women through the existing There is also a Special Biotechnology Award programmes and schemes of the Scheme for encouraging outstanding Department. The assessment is to be Women Scientists, In addition, under other reflected in the Annual Report of the schemes quantification regarding number of Department. women beneficiaries has been done in respect of M.Sc./M.Tech. Biotechnology • To come up with specific schemes teaching programme, Biotech Industrial targeted towards women. Training Programme, fellowships for doctoral and post doctoral research, awards, • To clearly bring out scheme-wise overseas associateship schemes and other provisions and physical targets for awards including travel support, Star benefitting women in the Annual Plan Colleges, Project Investigators (PIs) in DBT and Performance Budget of the funded projects. The details of the gender Department. budgeting is as given below:

321 Annexures Annual Report : 2011-12

Scheme-wise Provisions and Physical Targets Benefiting Women

Total Expenditure No. of Budget Benefits earmarked S. Schemes Budget incurred to Women Estimates for for women during No Allocation support benefitted financial year 2011-12 for the women through 2012-13 to Year during various support women 2011-12 2011-12 activities during (Rs. in (Rs. in 2011-12 crore) crore)

1. Human Resource No separate The programmes Development 54 27 1000 budget is have been earmarked to supported for 2. Bioinformatics 19 9.14 32 support R&D, women. infrastructure 3. Biotech facilities Centres However, the strengthening, of Excellence and budget for capacity building, Programme support 27 15.22 98 women bioinformatics, programmes is etc. In addition, 4. R&D 394.40 55.60 405 being spent special award from the total schemes have 5. Biotechnology for 13.00 4.47 7011 budget been initiated to Societal Development allocated for encourage women the year 2011- scientists and 6. International Cooperation 25 9.80 22 12 students.

322 Annual Report : 2011-12 Biotechnology Information SystemAnnexures Network Annexure-V (Rs. in Crore) RE 2011-12 Non- Non- BE 2011-12 Non- 2010-11 12.31 12.31 0 14.67 14.67 0 14.45 14.45 Actual Expenditure 0.00 0.00 0.00 0.00 0.00 0.006.88 0.00 0.00 —- 6.88 0.00 0.10 0.00 0.10 0.10 0.00 0.10 Plan Plan TOTAL Plan Plan TOTAL Plan Plan TOTAL 53.00 1.6044.00 0.4024.00 54.60 0.00 58.0024.00 44.40 1.80 0.00 37.0023.25 24.00 59.80 0.45 0.00 29.00 24.00 58.0025.00 37.45 0.00 29.00 23.25 1.80 0.00 33.00 29.00 0.00 29.0020.00 59.80 0.45 35.00 25.00 29.00 0.00 0.0032.00 33.45 0.00 29.00 24.00 29.00 0.00 20.00 35.00 0.00 0.00 22.00 13.00 32.00 29.00 0.00 24.00 0.00 28.00 35.00 22.00 13.00 0.00 0.00 13.00 28.00 35.00 0.00 22.00 13.00 0.00 22.00 1120.55 24.31 1144.86 1400.00 26.92 1426.92 1350.00 26.70 1376.70 Financial Statement for Annual Report: 2010-2011 National Centre for Cell Science Centre for DNA Finger Printing and Diagnostics National Brain Reseach Centre National Centre for Plant Genome Research Institute of Bioresources & Sustainable Development Translational Health Science & Technology Institute Rajiv Gandhi Centre for Biotechnology National Institute of Immunology Institute of Life Sciences Services SecretariatInstitution 0 REVENUE SECTION 2.02 2.03 2.04 2.05 2.06 2.08 2.09 2.01 2.07 1 Secretariat Economic 1.01 2 Autonomous R & D 1 2 3 4 5 6 7 8 12 13 14 S. Name of the NO. Programmes/Schemes

323 Annexures Annual Report : 2011-12 RE 2011-12 Non- Non- BE 2011-12 Non- 0.00 0.00 0.00 0.00 2010-11 Actual Expenditure Actual 0.50 0.00 0.50 14.00 0.00 14.008.68 14.00 0.00 0.00 14.00 8.68 15.00 0.00 15.00 13.00 0.00 13.00 Plan Plan TOTAL Plan Plan TOTAL Plan Plan TOTAL 29.26 0.0020.00 29.26 0.0012.38 34.00 20.00 0.00 0.0016.00 34.00 34.00 12.38 0.00 0.00 34.00 24.00 34.00 16.00 0.00 0.00 25.00 23.00 34.00 24.00 0.00 0.00 25.16 25.00 23.0054.58 0.00 23.00 0.00 25.16 26.70 0.00 0.00 54.58 23.00 63.00 26.70 0.00 27.00 63.00 0.00 70.00 27.00 0.00 27.00 70.00 0.00 27.00 330.27 2.00 332.27 376.10 2.25437.37 378.35 0.00 368.26 437.37 2.25 418.90 370.51 0.00 418.90 420.00 0.00 420.00 for Education and Training, Faridabad National Agri-Food Biotechnology Institute & Bioprocessing Unit, Mohali Institute for Stem Cell Research & Regenerative Medicine, Bengaluru National Institute of Biomedical Genomics, Kalyani National Institute of Development Bioinformatics Research & Development Animal Biotechnology, Hyderabad Total = Autonomous R&D Institutions Scientific Bodies Human Resource Biotechnology for Societal Development 12.1 2 UNESCO Regional Centre 3 4 5 6 7 8 12 13 14 2.11 2.12 2.13 2.14 3.02 3.03 3 Assistance to other 3.01 3.04 S. Name of the NO. Programmes/Schemes

324 Annual Report : 2011-12 Biotechnology Information SystemAnnexures Network RE 2011-12 Non- Non- BE 2011-12 Non- 2010-11 0.00 0.00 158.00 0.00 158.00 118.74 0.00 118.74 Actual Expenditure Plan Plan TOTAL Plan Plan TOTAL Plan Plan TOTAL 0.00 10.000.00 10.00 0.00 0.00 10.00 0.00 10.00 140.00 0.00 0.00 10.00 140.00 10.00 135.00 0.00 135.00 64.74 0.0051.0030.00 0.00 64.74 0.00 59.00 51.0092.52 30.00 0.00 54.00 0.00 36.00 59.00 0.0024.69 92.52 0.00 54.00 54.00 0.00 0.00 36.00 20.00 55.00 24.69 46.00 54.00 0.00 0.00 0.00 33.00 20.00 55.00 46.00 0.00 12.00 0.00 33.00 31.00 12.00 0.00 31.00 1120.55 24.31 1144.86 1400.00 26.92 1426.92 1350.00 26.70 1376.70 Sector - Assistance for Tech. Incubators, Pilot project, Biotechnology Parks Grand Challenge Programmes Programme For Promotion of Excellence & Innovation Biotech Facilities I&M Sector - Public Private Partnership schemes for the benefit of North Eastern Region and Sikkim TOTAL = Revenue 1 2 3 4 5 6 7 8 12 13 14 Section 5 International Cooperation 3.06 3.07 4.01 M & I 4.02 67 I.C.G.E.B Provisions for projects/ 3.05 S. Name of the NO. Programmes/Schemes

325 Annexures Annual Report : 2011-12

Annexure – VI List of patents filed/ granted during 2011-2012

National Institute of Immunology, New of said dkk3 in spermatogenesis and sex Delhi reversal. Patent application No. U.S. 13/ 102,682 dated 06.05.2011. 1. Recombinant sp_0845 protein as an anti- pneumococcal vaccine. Patent 6. A Novel typhoid vaccine eliciting application No. 1047/DEL/2011 dated memory antibody response from single 11.04.2011. dose immunization. Patent application No. 1539/DEL/2011dated 30.05.2011. 2. Isolation, cloning, sequencing and functional analysis of beta-casein 7. A Sortase-Click Reaction Suite for promoter along with the regions of Defined Protein Dendrimer Assembly: exon1, intron1 and exon2 using Synthetic Example of a Multivalent mammary gland derived cell line of Vaccine. Patent application No. 3113/ buffalo (Bubalus bubalis). Patent DEL/2011 dated 01.11.2011. application No. 1112/DEL/2011 dated 15/4/2011. 8. Monoclonal antibody specific to hemagglutinin from influenza virus h1- 3. Rhodanine compounds as tubulin subtypeand uses thereof. Patent binding anti- cancer agent and their application No. 3799/DEL/2011 dated application in treating cancers. Patent 23.12.2011. application No. 1167/DEL/2011 dated 20.04.2011. Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 4. Synthetic peptides and random copolymers for the treatment of 1. A method for synthesis of dendrimer autoimmune disorders. Patent polymeric resins for Solid phase peptide application No. 1313/DEL/2011 dated synthesis, Indian Patent No. 248244 05.05.2011. granted.

5. Knock down model of dickkopf 2. A Mouthwash Composition for homologue 3 (dkk3) for assessing role Managing Oral Mucositis, Process and

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Methods Thereof. Patent Application No. List of Patents filed/ granted under DBT PCT/IB2011/054877 dated 03.11.2011. funded projects during 2011-12

Centre for DNA Finger Printing and 1. Silk protein blend film development and Diagnostics, Hyderabad commercialization for burn wound management. Filed in India: Application 1. A method of altering levels of plasmids. No. 367/CHE/2007; filing date: 23/02/ Indian Patent 246791, granted on 2007 16.03.2011. 2. Tissue engineering of homologus natural 2. Virus resistant transgenic silkworms. biomaterial for clinical use. Indian Patent filed on 4.06.2011. • Filed in PCT: Application No. PCT/ National Centre for Cell Sciences, Pune IN2008/000404; Filing date: 25/06/08 for small diameter vascular graft from 1. Creation of Artificial Bone-Marrow processed cadaver cephalous vein and Environment and Uses Thereof: Application No. PCT/IN2008/000405; International patents have been filed in Filing date: 25/06/08 for Amniotic various countries. Granted and sealed Membrane. in New Zealand. • Filed in India: Application No. 2221/ 2. Preservation of Human hematopoietic CHE/2007; Filing date: 25/06/08, stem/progenitor cells using mannose (G.136) for Amniotic Membrane and binding lectins of plant origin. Indian Application No. 2222/CHE/2007; Filing patent sealed. International applications date: 25/06/08 (G.137) for small being defended by DBT diameter vascular graft from processed cadaver cephalous vein

Translational Health Science and 3. Development of a platform for Technology Institute, Gurgaon production of complex peptides and proteins, filed two patents in India: A method and device for detection of anti- • transglutaminase antibodies. Patent filed Application No. 3211/MUM/2010; Title: Application No. 1133/DEL/2011 Expression of complex proteins in yeast;

327 Annexures Annual Report : 2011-12

Purpose: To cover expression and Canada, China, EPO, Indonesia, Japan, production of recombinant human Malaysia, Philippines, South Africa, prethrombin in yeast and production of South Korea, Srilanka, USA and human thrombin. Vietnam.

• Application No. 3213/MUM/2010; Title: 7. Continuous Countercurrent Fluidized Yeast expression platform for expression Moving Bed (FMB) and/or Expanded of complex proteins and metabolites; Moving Bed (EMB), PCT Application Purpose: To cover the novel yeast No. PCT/IN2010/000133: Entered expression platform developed by the national phase in US, Korea, China, company that overexpresses 3 Canada and EPO. chaperones, the overexpression of each of which can be controlled - leading to 8. Complete Specification filed for “A proper folding and high expression of process for isolation of natural and target protein (Ex: Human Serum bioactive proteins and other minor Albumin), in yeast. components from defatted oil seed materials” following provisional 4. Novel methods of isolation of application No. 3577/MUM/2010. biochemicals from crustacean exoskeleton. Filed in India: Application 9. Indian Patent Granted for “A Process No. 1153/CHE/2008; Filing date: 16/10/ for Purification of Immunoglobulins 08. using a Pseudobioaffinity Adsorbent” Application No. 635/ MUM/ 5. Design, synthesis, evaluation and 2006; Granted Patent No. 248707, date of

development of the Novel H3 and other grant 9 August 2011. GPC receptor ligands for various therapeutic applications. Filed in India: 10. Process for Fractionation of biomass; Application No. 3278/MUM/2011; Filing Application No: 1762/MUM/2010; PCT/ date: 23/11/2011. IN 2010/000634; Inventors: Lali, Arvind Mallinath; Varavadekar, JayeshSuman; 6. Method for Production of Fermentable Wadekar, Prathamesh Chandrashekher. Sugars from Biomass”, PCT Application No. PCT/IN2010/000355. Entered 11. A process for production of fermentable national phase in Australia, Brazil, sugars from lignocellulosic substrates

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(Indian Patent: Application No. 1348/ 16 A novel 2-3 dimensional fabrication DEL/2011) technique of microchannels in soft polymers using soft lithography 12. The Art, Method, Manner, Process and technique, Indian patent System of Chitosan hydrogel/Nano Zinc Oxide Membranes for Wound Dressing 17. Integrated dielectrophoresis based rapid Applications. Indian Patent, File. No. concentration of pathogenic bacteria and 1025/CHE/2010, Date.12th April, 2010. their quantitaion using Flourescence techniques, Indian Patent. 13. Filed a provisional Indian patent- “organic fertilizer from degradation of raw chicken-feather by iron-oxide 18. Infectious DNA vaccines against magnetic nanoparticle (mnp) bound â- chikungunya virus. US Patent keratinase”. Application number 1416/ Application Number: US2011/000001 kol/2011, dated 18.12.2010

19. Consensus sequences of chikungunya 14. Indian patent filed: 0033nf2011dated 09- viral proteins, nucleic acid molecules 05-2011 encoding the same, and compositions 15. United States patent has been granted and methods for using the same PCT and the title of the project “A process NO: PCT/US09/39656 for producing a bio-pesticide composition containing Trichoderma 20. Anti-Chikungunya monoclonal harzianum and Pseudomonas fluorescens” antibodies and uses thereof. Patent Patent No: US7,923,005B2 application number: 20110143333

329 Annexures Annual Report : 2011-12

Annexure-VII

List of Technologies developed/ transferred during 2011-2012

International Centre for Genetic Engineering M/s. Genotypic technology Pvt. Ltd., and Biotechnology, New Delhi Bangalore for the development of “Chickpea Expression Microarray”. 1. Cry 1Ac & Vip 3A gene products developed for Insect Resistance Medical Biotechnology: Infectious transferred to Nagarajuna Fertilizers and diseases Chemical Ltd. (MTA), India. An immuno-chromatographic rapid visual test named “Crystal TB confirm” for 2. Insulin - recombinant Gene product detection of tubercle bacilli in culture transferred to The United Laboratories, developed at University of Delhi South China Campus (UDSC).

3. Recombinant Hepatitis B Surface Antigen Aquaculture & Marine Biotechnology - recombinant Gene Product transferred to The United Laboratories, China RT-PCR kit was developed for diagnosis of fish nodavirus. National Institute on Plant Genome Research, New Delhi Biodesign Programme

Next Generation Challenge Programme on A faecal incontinence device has been Chickpea Genomics has generated whole developed under the Stanford-India chickpea transcriptome and transferred to Biodesign Programme.

330 Annual Report : 2011-12 Biotechnology Information SystemAbbreviations Network

ABBREVIATIONS

AAU Assam Agricultural University AcKA Acetate Kinase ACTREC Advanced Centre for Treatment, Research and Education in Cancer API Active Pharmaceutical Ingredients ARI Agharkar Research Institute ATM ataxia-telangiectasiamutated ATR ATM and Rad 3-related AVD Abnormal vaginal discharge BAC Bacterial Artificial Chromosome BBB Blood brain barrier BHU Banaras Hindu University BIBCOL Bharat Immunologicals and Biologicals Corporation Ltd BIF Bifidobacteria BIPP Biotechnology Industry Partnership Programme BIRAC Biotechnology Industry Research & Development Assistance Council BIRAP Biotechnology Industry Research Assistance Programme BMI Body mass index Bp Base pair BSL Biosafety level BT Behavioural Therapy BUILDER Boost to University Inter disciplinary Life Science Departments for Education and Research Scheme BY 2 Tobacco bright yellow cell line CA Controlled storage Caco2 Colorectal adenocarcinoma cells CARI Central Avian Research Institute

331 Abbreviations Annual Report : 2011-12

CCMB Centre for Cellular and Molecular Biology CD4 Cluster of differentiation CDFD Centre for DNA Fingerprinting and Diagnostics CDHA Calcium deficient hydroxyapatite nanocarriers. CDSA Clinical development service agency CEB Centre for Energy Bioscience CFU Colony forming units CHO Chinese Hamster Ovarian cell line CI chymotrypsin inhibitory CIBA Central Institute of Brackishwater Aquaculture CIFA Central Institute of Freshwater Aquaculture CIMAP Central Institute of Medicinal and Aromatic Plants CIPHET Central Institute of Post Harvesting and Technology CIRB Central Institute for Research on Buffaloes COE Centres of Excellence CPP’s Caseinophosphopeptides CPPRI Central Pulp & Paper Research Institute CSFR Cassava Starch Flour Residues CSRTI Central Sericultural Research & Training Institute CSSRI Central Soil Salinity Research Institute CTAB Cetyl Triethyl Ammonium Bromide CTCRI Central Tuber Crop Research Institute CTEP Conferences, Travel, Exhibitions and Popular Lectures DFE Dairy and Food processing Engineering DNA Deoxyribonucleic acid DNAJB6 DnaJ homolog subfamily B member 6 DRR Directorate of Rice Research DU Delhi University

332 Annual Report : 2011-12 Biotechnology Information SystemAbbreviations Network

E.coli Escherichia coli EBF Early B cell factor EhCaBP Entamoeba histolytica calcium-binding protein ELISA Enzyme Linked Immunosorbant Assay EPD Electrophoretic deposition EPN Entomopathogenic Nematodes ERá Estrogen Receptors Alpha ESE1 Epithelium-Specific ETS transcription factor-1 EST expressed sequence tags; ETS Erythroblast Transformation Specific FAME Fatty Acid Methyl Ester FCR Feed Conversion Ratio FFA Free Fatty Acid FPE Food Processing engineering FSH Follicle Stimulating Hormone FTIR Fourier transformation infrared spectroscopy FVM Finite Volume method GADVASU Guru Angad Dev Veterinary and Animal Sciences University GBPUAT Govind Ballabh Pant University of Agriculture and Technology GCSF Granulocyte Colony Stimulating Factor GL Ganoderma lucidum GMO Genetically modified organisms GNP Gold Nanoparticles GSI Gonado Somatic Index GST Glutathione S- Transferase GUS beta-glucuronidase; HAMP Histidine kinases, Adenylyl cyclases, Methyl binding proteins, Phosphatases h-BRCA1 Human Breast-Cancer-Associated Gene 1

333 Abbreviations Annual Report : 2011-12

hCG Human chorionic gonadotropin hGBPI human Guanylate Binding Protein-1 HIV Human Immuno Deficiency Virus HPLC High performance liquid chromatography Hsp70 Heat Shock Protein 70 IARI Indian Agriculture Research Institute IAVI International AIDS Vaccine Initiative IBD Inflammatory bowel disease IBIN Indian Bioresource Information Network IBSD Institute of Bioresources and Sustainable Development IC International Collaboration IC50 Half maximal inhibitory concentration ICAR Indian Council of Agricultural Research ICGEB International Centre for Genetic and Engineering Biotechnology ICRISAT International Crops Research Institute for the Semi-Arid Tropics ICT Institute of Chemical Technology, Mumbai IDA International Depository Authority IF1, 2 Initiation Factor 1 and 2 IFNã Interferon-gamma IGFRI Indian Grassland and Fodder Research Institute IGIB Institute of Genomics and Integrative Biology IHBT Institute of Himalayan Bioresource Technology IIAR Indian Institute of Advanced Research IICT Indian Institute of Chemical Technology IIHR Indian Institute of Horticulture Research IIMT Indian Institute of Minerals Technology IISc Indian Institute of Sciences IISER Indian Institute of Science and Education Research

334 Annual Report : 2011-12 Biotechnology Information SystemAbbreviations Network

IIT Indian Institute of Technology IL-1 Interleukin-1 ILS Institute of Life Sciences INFâ Interferon-beta INM Integrated Nematode Management iNOS Inducible Nitric Oxide Synthase InStem Institute for Stem Cell Biology and Regenerative Medicine IOCL Indian Oil Corporation Limited IPM Integrated Pest Management IRRI International Rice Research Institute IU International unit IVCOL Indian Vaccines Corporation Limited IVRI Indian Veterinary Research Institute IVTD In vitro true digestibility IYBA Innovative Young Biotechnologist Award JNU Jawaharlal Nehru University LAB Lactic acid bacillus LDC leprosy-derived corynebacteria LEEP Loop electrical excision procedure LOI Letter of intent MAMC Maulana Azad Medical College MAP Mitogen-activated protein MCC Microbial Culture Collection Centre MCF 7 Breast cancer cell line and MIRS Multiple Insecticides Tolerant (resistant) Strain MKU Madurai Kamaraj University mRNA Messanger Ribo Nucleic Acid MSSRF MS Swaminathan Research Foundation

335 Abbreviations Annual Report : 2011-12

Mtb Mycobacterium tuberculosis MVC Madras Veterinary College

N2a Neuroblastoma cell line, NABI National Agri-Food Biotechnology Institution NARI Nimbakar Agricultural Research Institute NBAGR National Bureaue of Animal Genetic Resources NBDB National Bioresource Development Board NBRC National Brain Research Centre NBRI National Botanical Research Institute NCBS National Centre for Biological Sciences NCCS National Centre for Cell Sciences NCI H 460 Lung cancer cell line NCIM National collection of industrial microorganisms NCL National Chemical Laboratory NDRI National Dairy Research Institute NEERI National Environmental Engineering Research Institute NEHU North East Hill University NFkB nuclear factor kappa-light-chain-enhancer of activated B cells NGS Next Generation Sequencing NH Nerve cell homing NIAB National Institute of Animal Biotechnology NIBMG National Institute of Biomedical Genomics NII National Institute of Immunology NIIST National Institute for Interdisciplinary Science and Technology NIPGR National Institute of Plan Genome Research NIRRH National Institute for Research in Reproductive Health NLS Nuclear Localization Signal NMR Nuclear magnetic resonance

336 Annual Report : 2011-12 Biotechnology Information SystemAbbreviations Network

NRC National Research Centre NRCPB National Research Centre on Plant Biotechnology NTFP Non-timber Forest products OMP Outer Membrane Protein OPV Oral Polio Vaccine ORT Oral rehydration therapy PaLCuV Papaya leaf curl virus PAT Process Analytical Technology PAU Punjab Agriculture University PCR Polymerase chain reaction PDA Potato dextrose agar PDP Project Directorate on Poultry PduW/TdcD Propionate acetate kinase PEO Plasma Electrolytic oxidation PGE2 Prostaglandin E PGN Peptidoglycan PGPR Plant Growth Promoting Rhizobacteria PHA Polyhydroxyalkanoate PHE Post harvest engineering PI Proteinase Inhibitory PNA Peptide nucleic acid PPIases Peptidylpropyl isomerases q PCR quantitative Polymer Chain Reaction QTL Quantitative Trait Locus R&D Research & Development RAP80 Receptor Associated protein 80 RAPD Random Amplification of Polymorphic DNA RBD Random Block Design; RNA: ribonucleic acid RCGM Review Committee on Genetic Manipulation

337 Abbreviations Annual Report : 2011-12

rDNA recombinant deoxyribonuclies acid RGCB Rajiv Gandhi Centre for Biotechnology RHD Rheumatic Heart Disease RIP Receptor Interacting Protein

RNA Ribo Nucleic Acid

RRF Ribosome Recycling Factor rRNA Recombinant Ribonucleic Acid

RT- PCR Real Time Polymerase Chain Reaction

SAM Severe Acute Malnutrition

SAU State Agricultural University

SBIRI Small Business Innovation Research Initiative

SBRL Seri Biotech Research Laboratory

SC Schedule Caste

SD Standard Deviation

SDS PAGE Sodium Dodicyl Sulphate Polymerase Acryl Gel Electrophoresis

SGPGIMS Sanjay Gandhi Post Graduate Institute of Medical Sciences

SHG Self Help Group

SiRNA Small Interfering RNA

SKUAST Sher-e-Kashmir University of Agricultural Sciences & Technology

SL Structures lipids

SLE Systemic Lupus Erythematosus

SNB 19 Human Embryonic cells- Normal cells

SNP Single-Nucleotide Polymorphism;

SRI Systemic Rice Intensification ST Schedule Tribe SVVU Sri Venkateswara Veterinary University TANUVAS Tamil Nadu Veterinary and Animal Sciences University TERI The Energy and Resources Institute

338 Annual Report : 2011-12 Biotechnology Information SystemAbbreviations Network

THP-1 Human acute monocytic leukemia cell line THSTI Translational Health Science and Technology Institute TI Trypsin inhibitory TNAU Tamil Nadu Agriculture University TNFá Tumor Necrosis Factor alpha UAS University of Agricultural Sciences UCS University College of Science, Kolkata UDSC University of Delhi South Campus, New Delhi UOH University of Hyderabad URL Uniform Resource Locator VIA Visual Inspection by Acetic Acid VMSRF Vittal Malaya Scientific Research Foundation WDCM World Data Centre for Microorganism WF Weaning foods WFCC World Federation for Culture Collection WHO World Health Organization WIPO World Intellectual Property Organization WSSV White Spot Syndrome Virus

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