REPORT Highlight on NIBN Establishing Why the NIBN NIBN Prof. Varda Shoshan-Barmatz Prof. Irun R. Cohen, MD, Director Deputy Director Prof. Sir Aaron Klug, OM, FRS Many have asked how Israel might succeed The National Institute for Biotechnology in in achieving greater returns in intellectual the Negev (NIBN) is proud to publish this Chair of the International NIBN REPORT. Advisory Committee property and biotechnology products for a The purpose of the NIBN REPORT is to given investment in basic research in the summarize the progress and achievements It is now five years since we first made life sciences. Or to be more specific, why of the NIBN, which is at the spearhead of the approach to the Government for do I think the NIBN will be more effective the University's efforts to promote excellence funding a National Institute of than previous efforts in launching successful in research. The NIBN, made possible biotechnology. I shall answer that question Biotechnology in the Negev at BGU. through the magnanimous support and by summarizing the problems inherent in vision of Dr. h.c. Edgar de Picciotto of The basis was to be the Institute of Applied the relationship between university research Switzerland, brings together scientists from Biosciences which had been built and and biotechnology to clarify the rationale different disciplines with medical personnel funded with the generous support of of the NIBN model and its implementation. and professional consultants to create a Dr. h.c. Edgar de Picciotto of Geneva. front-line interdisciplinary institute focusing University and Biotechnology on biotechnology. It was his vision that this Institute could in Conflict of Interest Revolutions come in stages, and we have and would form the nucleus of a future now advanced from the first stages of National Center for Biotechnology. The University adoption of new ideas, tools and methods. Although there was a generally favourable Classically, universities have been designed We would like to express our thanks and to fulfill two primary functions: research recommendation from the Government appreciation to Prof. Sir Aaron Klug OM and teaching. University research in its FRS, who served as Acting Executive departments and acceptance in principle, broadest sense extends beyond laboratory Director of the NIBN, and members of the no money was forthcoming. experimentation to include the convocation International Advisory Committee: Prof. We nevertheless continued to plan that it Yehudit Birk, Prof. Aaron Ciechanover. of scholars and the provisions they need to Prof. Raymond Dwek FRS and Prof. Philip would eventually happen, and were very advance and disseminate collective Needleman, all of whom represent a fortunate to gain generous support from knowledge and understanding in the reservoir of experience, information and the Morris Kahn Humanitarian Fund, humanities, arts and sciences. University authority and have an important impact on teaching prepares coming generations of originally for a program in the Faculty the development and achievements of the professional scholars and educates the non- of Health Sciences initiated by Professor NIBN. professional members of society as well. The strong point of the NIBN has been Rivka Carmi on the genetic approach to The pursuit of research and teaching has its ability to recruit outstanding young human health. This was later expanded dictated the organization of universities into scientists. These talented researchers are to recruit outstanding young researchers specific departments and faculties and has supported by NIBN's overall commitment led to the prevalent operational machinery to invest in the technical infrastructure for in cognate subjects and to provide new sophisticated state-of-the-art biotechnology instrumentation. (department heads, deans, committees, laboratories. This combination has made Two years ago,these two funding senate, rector, and so forth) for academic decision-making regarding funding, the NIBN one of the most attractive research initiatives came together, and, as Chair centers in Israel today and this REPORT appointments, evaluations, advancement, contains a brief summary of some of their of the International Advisory Committee, and tenure. This university structure oversees exciting and innovative achievements I took up the position of Acting Executive the responsibility of the staff for teaching, This issue includes an article by NIBN's Director while we searched for a Director scholarly achievement and publishing. newly appointed director, Prof. Irun Cohen, of NIBN. We were able to attract who 30 years ago was a member of the team Biotechnology that founded BGU's Faculty of Health Professor Irun Cohen to that position, Biotechnology strives to fulfill a different Sciences. The article, focusing on "Why with his deputy, Professor Varda Shoshan- agenda: Biotechnology focuses on the Biotechnology and Why in the Negev" Barmatz, who throughout the years has discovery and development of technologies, addresses very important questions and their worked indefatigably towards our aim. devices, and reagents that tend to the answers in one line: this is the right time, I also wish to thank my fellow members biological needs of humans for sustenance, the right place and the right decision. health, and enlightened economic welfare. of the International Advisory Committee, We believe that NIBN will create a Biotechnology has little or no interest in significant impact on the economic particularly Professors Raymond Dwek university teaching or research – except for prosperity of the Negev region and and Philip Needleman, who brought their throughout Israel. NIBN will fuel spin-off the specific research or teaching that is part wide ranging expertise to the project. companies, incubator programs and of a defined product goal. Biotechnology accelerator corporations will be established We look forward to the event this week is not interested in professorships, to commercialize the novel ideas and which highlights NIBN and at which publications, or the operational machinery technologies at the NIBN. The interaction Dr. h.c. de Picciotto and Minister Ehud of university departments, deans, and combination of academic merit with committees, senates, and rectors. Indeed, Olmert will formally announce long term economic prosperity will attract scientific much of the university activities carried out excellence and serve as a hub for research, funding for NIBN, enabling the Institute 2 by the researcher can interfere with his or development and teaching in the Negev. to enter a new phase of development. her participation in the biotechnology enterprise. But despite the conflict of performance. Affiliates outside the advanced position. The key issue is interest, biotechnology still depends on university are recruited to join the various implementation. university researchers and their ideas, NIBN groups as needed. Networks, local Implementation expertise, technical staff and research to and international, are established to further The success of the NIBN model will depend thrive. University researchers are the the programs. The NIBN is situated within on three factors: excellence, collaboration innovators of most successful biotechnology BGU and staffed by BGU scientists, but it and resources. products. In short, biotechnology needs the is significantly independent of the traditional Excellence. The success of the NIBN university. university department/faculty structure. depends greatly – perhaps entirely – on the Universities too, until recently, have shown NIBN Programs continuing recruitment of outstanding no interest in biotechnology, which is usually The biotechnology programs being scientists from among the talented young foreign to the pursuit of teaching and basic, developed at the NIBN embody the concept Israelis returning from advanced training disinterested research. Despite the conflict of multidisciplinary convergence. NIBN abroad. The NIBN will continue to attract of interest, however, universities have biotechnology, like converging technologies such talent only if it can compete with other discovered the economic value of intellectual being developed in the USA, the European institutions in Israel and abroad in providing property developed at the university; Union and elsewhere, cuts across academic opportunity, and not only in offering a successful university biotechnology can boundaries. The NIBN staff is rich in challenge. It is especially gratifying to note provide funds much needed by the university multidisciplinary expertise: that the NIBN has succeeded in recruiting to carry out its traditional agenda of The Human Genetic Diseases program talented young Israelis who have been education and scholarship. The university mixes clinical and molecular technology to offered staff positions abroad at frontline benefits from biotechnology. discover novel genes and generate gene institutions. These scientists share an Interdisciplinary and converging products that promise to lead to therapies appreciation for the importance of the NIBN technologies for several health problems; model. Indeed, in the past month, the NIBN Not only is biotechnology at variance with The Glycobiology program is based on has been joined by an Israeli scientist the teaching and basic research missions of advanced carbohydrate chemistry and returning from two years as the head of a the university, biotechnology is inherently proteomics, and hosts the National Center central systems biology unit at Harvard. multidisciplinary and interdisciplinary, and for Glycobiology, providing a unique service Collaboration. Not only must the NIBN so crosses the barriers of traditional academic to Israel industry along with its development attract excellent staff scientists, the NIBN subdivisions. The technological crossing of of novel approaches to diagnosis; must provide the physical and intellectual academic barriers has been called The NIBN has established an electron environment needed to bring this talent to convergence. Convergence, or Converging microscopy tomography unit that exists in work together. To this end, the NIBN Technology has been defined as the need only three other locations worldwide. This research leaders hold weekly meetings with for academically independent fields of advanced device adds front-line structural NIBN management aimed at fostering science and technology to work together to imaging technology to the development of mutual participation and collaboration. create innovative ideas and products. health applications; Monthly research seminars are held for all To succeed in multidisciplinary problem The Microbial Biotechnology program the students, technicians and associates as solving, biotechnology needs an exploits molecular genetics along with its well as for the scientists. The NIBN provides interdisciplinary organizational structure new technology for cultivating previously competitive grants for selected interdiscip- foreign to the department/faculty makeup un-culturable bacteria as a means to obtain linary projects. These and other measures of the present university model. useful microbial products; are undertaken to promote convergence and Bio-materials and tissue engineering have interdisciplinary problem solving. The NIBN Model provided tissue scaffolds for the regeneration Resources. To attract and maintain an The NIBN has been conceived as an of heart muscle or bone in patients suffering outstanding staff, the NIBN must be able to innovative model to circumvent or resolve from a loss of the tissue and its function. deploy its own sources of funding to enable the traditional conflict of interest that Nanotechnology directed to bio-sensors is it to purchase frontline equipment, support estranges the university from interdis- part of the NIBN program in bio-materials. technicians, students and fellows for ciplinary, converging biotechnology. The Immune biotechnology mines information advanced research, and provide suitable NIBN is structured as a collection of from the immune system to develop space for a critical mass of multidisciplinary multidisciplinary task forces culled from all therapeutic approaches to Alzheimer’s and researchers. Intellectual property generated the different faculties at BGU, but yet the other chronic diseases. IVRI, the Israel by NIBN science will return in part to the NIBN remains free of the need to concern Vaccine Research Initiative, with affiliates scientist inventors and to the NIBN, as well itself with promotions, tenure, and other abroad and throughout Israel, is closely as to the university. A successful NIBN will parochial academic concerns. connected to NIBN immune system ultimately generate much of its own funding. The NIBN operates through multidiscip- biotechnology. A substantial endowment, however, is linary channels of communication and Informatics is essential to biotechnology; needed now to sow the seeds for commercial collaboration, relatively free of departmental informatic tools are indispensable to enterprises. Moreover, a building suited to concerns. Indeed, membership in the NIBN, integrating, manipulating and understanding the interdisciplinary needs of a converging unlike tenured membership in a department, the complexity of the living organism. biotechnology needs to be built to house the is subject to regular review and adjustment: Thus the NIBN is already on the way NIBN; a well-designed building will itself staff earn membership and can have it towards fulfilling the promise of convergent attract excellent researchers and provide the withdrawn as judged by outside evaluation biotechnology. Its multidisciplinary NIBN with a competitive advantage in of the appropriateness of the research activities and its multi-faculty organizational performance. 3 program and the excellence of the scientists’ structure place the NIBN in a uniquely Exploring the Inner-space of Cells at the NIBN Ohad Medalia, Ph.D Visualization of the three-dimensional (3D) The challenge I faced was to establish an because of a lack of resolving power. organization of a eukaryotic cell, with its electron microscopy facility that can Indeed, while traditional 2-D electron dynamic internal structure and distinct compete with the best electron microscopy microscopy has been an applied to the study protein complexes in their native context, laboratories in the world. of the actin content in cellular protrusions, requires a non-invasive imaging technique At a cost of $2.8 million dollars, BGU only ET with its 3D view of this network of high resolution combined with a means acquired the 300kV electron microscope in an unperturbed state possesses the for arresting cellular elements in their which is housed in the NIBN. This facility potential to reveal the secrets of cell motility. momentary state of function. Electron is unique to Israel and one of seven A major project in my lab, therefore, is to tomography (ET) is such a method, worldwide. It will be used to gain new elucidate the 3D structure of the adhesion possessing, in addition, a unique potential insights into the lesions of Alzheimer's machinery of cells. for 3D visualization of large pleiomorphic Disease and other chronic conditions. 2. Structural analysis of the nuclear structures such as intact cells and appears Recently, we were able to generate the periphery, the nuclear pore complex and likely to revolutionize the way cells are first cell reconstructions that gave us our the nuclear lamina. The cell nucleus is an viewed. first 3-dimensional glimpse into the extremely complex compartment that is After three years of post-doctorial training phtosythetic system in bacteria. responsible for many processes in a living at the Max-Planck institute of Biochemistry, In my laboratory, we apply cryo-electron cell. However, its organization, at the where I focused on cryo-ET of eukaryotic tomography to intact cells, focuing on two nanometer scale, is still uncharted territory. cells, I had to decide on my next scientific main goals: 1. Reconstructing the eukaryotic While much has been learned, in recent step. The possibilities were to accept an cytoskeleton in 3D- Cell motility relies on years about the movement of soluble academic position at: 1. The European fast and regulated polymerization/depoly- transport factors across the nuclear pore Molecular Biology Laboratories (EMBL), merization of actin filaments that push the complex (NPC), high resolution structure Heidelberg. 2. The Weizmann Institute of plasma membrane. Using live cell imaging of these large macromolecular assemblies Science. 3. The Hebrew University 4. The techniques, many of the factors contributing is still not available. Since a clear picture Ben-Gurion University and the NIBN. to this dynamic process have been revealed. of the molecular organization and dynamics I joined the BGU and the NIBN in March Nevertheless, due to the dimensions of actin of the NPC is one of the basic elements 2005, because it is the most dynamic and filaments and the density of the filamentous required to resolve the mechanism of the only academic institution in Israel that network, important aspects of this important transport within cells, a major emphasis in 4 is developing with an eye to the future. mechanism have remained unsolved, in part, my lab is to produce a high resolution map of these complexes. The Bioinformatics Support Unit Vered Caspi, Ph.D

During the last decade and with accelerating The Bioinformatics Support Unit was speed, biological sciences are undergoing founded on September 2003 by Dr. Vered a transformation, whereby extremely large Caspi, who was recruited from the datasets are being generated experimentally, Weizmann Institute where she was one of stored in international databases and being the founders of the GeneCards database for integrated for a wide variety of uses. The human genes. More recently, the Unit was emergence of bioinformatics. has thus expanded with the recruitment of Dr. Daniel evolved; a multi-disciplinary field integrating Harari, an experienced bioinformatician and a blend of biological, mathematical and molecular biologist from both academia and computer sciences, providing the opportunity industry, Mr. Raphael Cohen, a third year to accelerate the discovery process for the Bioinformatics student at BGU who works biological, biotechnological and biomedical as a system administrator and programmer, sciences. Israel is an internationally as well as a number of under-graduate recognized center of excellence in teaching assistants and project students. bioinformatics. Even so, there remains a great par that separates the knowledge-base The Unit activities include: of most Israeli biologists and the emerging Conducting weekly workshops on Statistical analyses of microarray bioinformatics applications relevant to practical usage of bioinformatics tools. experiments run at the NIBN microarray particular biological fields. With this in Teaching 3 academic semester courses facility and elsewhere. mind, the Bioinformatics Support Unit was to both undergraduate & graduate Maintenance of a computer server established at BGU with the major role of students. containing cutting edge bioinformatics helping university biologists to become One-on-one research consultation and software and databases for the use of acquainted with bioinformatics tools, and support to scientists and students. the BGU community. to keep the more informed scientists updated Research collaborations on large-scale with recent developments in bioinformatics analyses of entire genomes. These activities are crucial for enhancing technologies, in order to advance research Development of automated software for the biotechnological potential of the NIBN efforts. functional genome analysis. and the larger BGU.

A Year in the NIBN Alon Monsonego, Ph.D

My scientific career was initiated at the It was then clear to me that the next step Weizmann Institute where I studied in my scientific carrier should be in Israel. mechanisms of wound healing of the central The NIBN opened a unique and very nervous system as part of my Ph.D. thesis. challenging opportunity to reach my goals. Toward the end of this educational stage, It first allows one to function in a I began appreciating the significant multidisciplinary unit which forms new importance of our immune system to deal directions of research. Second, it generates with diseases of non-infectious origin such the ultimate combination between basic and as cancer, neurodegeneratation, and applied research. autoimmunity. I then moved to Harvard to During the first year at the NIBN, I obtain the state-of-the-art knowledge and established an almost fully equipped technologies required for basic laboratory based on generous funds from understanding of autoimmunity and the the NIBN and several national and dialog the immune system holds with the international scientific grants. As part of brain. I spent 5 years at Harvard (2 years our research program, our group established which otherwise would not have occurred. as post doctoral fellow and then 3 years as colonies of mouse models for Alzheimer’s In summary, we now wish to enter the a faculty member), during which I disease and multiple sclerosis and hopefully second phase at the NIBN towards gaining investigated novel immune mechanisms of these will enter an essential new facility novel aspects of autoimmune mechanisms Alzheimer’s disease and became one of the soon. Being exposed to the other groups at in general and neurodegenerative diseases leaders in the design of vaccination the institute, we have already initiated new in particular and thus designing new approaches to this disease. collaborations with 3 groups at the NIBN approaches for therapy. 5 From Harvard to NIBN Eitan Rubin, Ph.D System biology holds great promise for nearly one third of all group leaders came medical and agricultural research. from Israel. The root cause of this success Monitoring the components of life (genes is not fully clear to me, but it probably has and their products, cells and tissues) is not to do with the Israeli culture of collaboration, sufficient to predict the behavior of our flexibility in acquiring new skills, and biological systems. As a result, we still the ability of the nation (and friends) to cannot predict a patient's reaction to a new quickly re-allocate resources. Finally, it can drug, or the nutritional properties of a new also do with the large proportion of crop. Life is complex, and understanding computationally savvy scientists who enter how it reacts to perturbations requires universities in Israel: there are currently four understanding the dynamic interaction of degree programs in bioinformatics in Israel, many different molecules, cells, tissues and which combine biology and computer life systems biology. For example, Glycomics organs. Such an understanding is essential sciences training. research, spearheaded by the “Sugers group” both for the progress of biotechnology from Here at NIBN, my lab is marrying systems and Yoram Tekoa, is going to prove a a trial-and-error science into a true rational biology with another emerging field, medical limiting factor in systems biology; field. informatics. We are utilizing electronic mitochondria, as studied by the Dan Mishmar Scientists throughout the world are clinical records as a source of information group, is a peculiar subsystem which has developing the experimental, computational for systems biology research, specifically immense impact on the ability of cells and and conceptual breakthroughs required for the Soroka Clincal Repository, which gives tissues to perform their functions. But most the systemic study of life. First, they measure us information about how peoples' health importantly, we are currently working to in completeness the state of systems over change over time, how they respond (or not) join forces between researchers in the center time – collecting millions, billions and even to treatment, etc. We use these data as a and outside, in other parts of BGU, to harness trillions of data points in a single experiment. substitute to experiments in which the the Israeli spirit together with the Ben Gurion Harvard is a hub for such experiments: with phenotype (i.e. the observed state of the family spirit, and create a non-traditional an investment of $100 million (shared with system) is scored in completeness for a large interdisciplinary network including faculty MIT), the Broad Institute was established number of individuals. With some 600,000 from departments which traditionally do not specifically for this purpose. NIH provides individuals, we hope these data will allow collaborate with biologists. For example, we multi million dollars a year grants to the developing more detailed and structured found immense enthusiasm in the department Broad Institute, the Bauer Center for description of many diseases. We are using of Industrial Engineering and Management. Genomics Research and to other groups these data to study how a subset of disease To conclude, the move from Harvard to throughout Harvard to perform such large causing genes, about 12% of all human NIBN requires adapting to the relative lack experiments. These funds are being used to genes, can lead to disease regardless of of resources. I am convinced that by properly develop new technologies that would allow environment or other genes, while other relying on our competitive advantage as the measurement of all aspects of a system genes don’t. We are also working to develop Israelis and in BGU, and with help from simultaneously at a reasonable price, to use new disease sub-classification schemes (a funding agencies and donors, we will be able existing technologies (at unreasonable process known as disease stratification) to be leaders in this field, and to reap its prices) to obtain such data for the first time, which may prove crucial for clinical trials, fruits in facilitating biotechnology and to utilize these data to establish the identify new disease causing genes in silico., development in NIBN. We should and can computational and conceptual frameworks and help facilitate experimental gene be equal competitors to Harvard by the required for its analysis. identification through computational tools improved utilization of resources we can Israel has a major role in allowing this that predict which genes are more likely to secure for this purpose, most importantly field to flourish, especially in developing be related to a given disease. the wonderful and unique human resources the computational techniques it requires. At Others at NIBN are also working on that Israel provides. the Bauer Center for Genomics Research, projects which target crucial aspects of

6 Cryo-electron tomography of actin network, membranes and protein complexes inside the intact cell From University of California, Irvine to NIBN, Beer-Sheva Dan Mishmar, Ph.D During my PhD studies at the Department the association of human mtDNA variation of Genetics, Hebrew University, I was with type II diabetes mellitus (DM). intrigued by mechanisms of genome Recently we have shown that linked sets of instability, that underlie not only chromo- common mitochondrial DNA (mtDNA) somal breakage in cancer and several variants (haplotypes, haplogroups) are inherited disorders but also the formation subjected to positive selection, possibly of new chromosomal arrangements during driven by climate. Some of these variants speciation events in evolution. Studying were previously associated with age-related variants that may either cause genetic disorders (such as Parkinson and disorders or drive the evolution of species Alzheimer’s diseases) and others with (ROS) production using antioxidants and led me to Prof. Douglas Wallace’ laboratory successful prolonged aging. Thus we vitamins. in the University of California, Irvine, USA, hypothesized that common mtDNA variants The second line of research in my lab the world’s authority on human mitochon- affect mitochondrial energy metabolism focuses on elucidating the structural and drial genetics and diseases who identified and, in turn, alter the tendency to adapt to functional enigma of the first and largest the first human mitochondrial DNA (mt- changing environmental conditions, yet also protein complex of the mitochondrial DNA) mutation underlying mitochondrial affect susceptibility to develop age-related oxidative phosphorylation, Complex I. inherited diseases. After almost four years disorders. Most inborn errors affecting oxidative of postdoctoral training, I shaped and Several lines of evidence implicate the phosphorylation function result in complex focused my research on the role of involvement of mitochondrial dysfunction I dysfunction. Nevertheless, only meager mitochondrial genetic diversity in disease and mitochondrial genetics in the mechanism information exists for complex I structure and evolution. Having visited all the major underlying DM and its complications. By and function. Hence in this study, we set Universities in Israel, with offere of tenure- focusing on the association of mtDNA forth to analyze the function as well as track positions at Bar-Ilan and at the Hebrew genetic variation with complications in type possible tissue specificity of mitochondrial University, I chose to join the Department II DM, both epidemiological data and a complex I subunit activity. Our study will of Life Sciences and the NIBN at BGU. careful medical assessment of the disorder shed light on the structure and function of Now, after almost a year in BGU, I am in the affected subjects are fundamental. complex I and on the mechanism by which grateful for the opportunity provided to me We believe that this research will shed light it is involved in human mitochondrial to establish my lab in outstanding conditions. on the involvement of mtDNA common disorders. Moreover our study might open Moreover, the recruitment of several new variants in aging and on the genetic a path towards understanding the molecular excellent scientists has created a supportive inheritance of type II DM. Such information basis of tissue specificity in OXPHOS collegial environment leading to creativity will assist in the design of preventive disorders. Such an investigation may assist and fruitful interactions. treatment of the population at risk against in the design of therapeutic approaches for One of my research subjects focuses on mitochondrial Reactive Oxygen Species combatting this disease.

Fighting Human aspects of a signaling pathway in normal development. Having impressive similarity Diseases with Flies to the human genome (60% homology in Uri Abdu, Ph.D genes involved in human disorders), the fruit fly Drosophila has become a most After completing a PhD at the Department popular model organism for studying human of Life Sciences at BGU and a post-doctoral disease. Indeed, my research involves the training in developmental genetics in the use of Drosophila as a model system for Princeton University, I joined the studying human diseases including the Department of Life Sciences and the Unit leading causes of infertility and cancer. of Genetics at NIBN . NIBN clearly provided In my studies, I focus on defining the role me with an excellent starting point to of the DNA damage checkpoint proteins in perform my research in a competitive and mitotic cell division, a research directly effective manner, to build my scientific related to cancer biology. This research is career and nurture the next generation of supported by the Israel Cancer Research of female infertility. Utilizing the fruit fly scientists. Moreover, NIBN recruited Foundation (ICRF). allows investigating the function of specific outstanding scientists from different In a collaborative project with Dr. Ohad candidate genes that we have found to be disciplines which creates a unique Birk, we are investigating the molecular involved in the molecular basis PCOS. stimulating scientific environment. mechanism underlying the polycystic ovary Understanding such functions will lead, in Model organisms provide an opportunity syndrome (PCOS), affecting 5-10% of turn, to the development of therapeutic to examine the most highly conserved women of fertile age and the leading cause approaches targeting such genes. 7 Last Year NIBN Achievements

During one single year, NIBN scientists have published over 50 scientific articles in peer-reviewed journals including Science, Proceedings of the National Academic of Sciences and other high- impact publications.

NIBN scientists have made headlines by their cutting edge scientific presentations and have been registered over 20 patents. Genetics at NIBN Researchers at NIBN received in the last year about Ohad Birk, MD, Ph.D $3 million in competitive research grants. In addition, a grant of $3 million from DIP (Deutsche- The Genetics section of NIBN is focused on the Israelische Projektkooperation) for 5 years (to Dr. identification and characterization of genes associated with human diseases. O. Medalia). The research is of importance in three venues: One spin-off company was established (by A. Sagi, Medicine: provision of molecular diagnosis of and A. Berman) and the establishment of the second hereditary human diseases, enabling carrier detection and prenatal diagnosis. is in progress (osteoporosis diagnosis, V. Shoshan- Science: discovery of the molecular basis for human Barmatz). diseases, and of normal molecular developmental pathways. Two licensing agreements were established by Biotechnology: discovery of novel drug targets for the Prof. Smadar Cohen, one with BiolineRx company: treatment of those disorders. Such genes are of potential investment of $9 million and the other one with interest to big pharma companies as a basis for the an American company (option letter was signed in design of novel drugs. October 2005, finalization on December 2005). The studies are carried out through: 1. Linkage analysis of large inbred families, mostly of the Bedouin community of southern Israel. 2. Molecular analysis of chromosomal aberrations associated with specific human disorders. 3. Studies of mitochondrial function and mitochondrial molecular genetics associated with specific human disorders. 4. Microarray analysis of diseased vs normal tissues. 5. Functional genomic analysis (in-vitro and in-vivo) of disease-associated genes unraveled in 1-3 above. Once disease-associated genes are identified, studies of The National Institute these genes are carried out – from structural analysis of for Biotechnology in the Negev the encoded proteins and biochemical analyses, to cellular studies of mutated cells, to the generation and analysis Ben-Gurion University of the Negev of animal models of the diseases. Beer-Sheva, 84105, Israel Some of our findings of the past year include: Tel: 972-8-6461912 1. A novel gene associated with seborrheic dermatitis Fax: 972-8-6272983 and psoriasis. Web Site: http://nibn.bgu.ac.il 2. A novel gene associated with symmetric growth E-mail: [email protected] retardation. Director: 3. A novel gene associated with male infertility Prof. Irun Cohen (azoospermia). [email protected] 4. A novel gene associated with meconium ileus Deputy Director: (congenital intestinal obstruction) - relevant to Cystic Prof. Varda Shoshan-Barmaz Fibrosis, and possibly to constipation. [email protected]