Wellcome Trust Joins 'Academic Spring' to Open up Science
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
A DNA Database in the NHS: Your Freedom up for Sale?
A DNA database in the NHS: Your freedom up for sale? May 2013 In April 2013, the Caldicott Committee, including Government Chief Scientist Sir Mark Walport, proposed new rules for data-sharing which would allow the Government to build a DNA database of the whole population of England in the NHS by stealth.1 The plan is to make NHS medical records and people’s genetic information available to commercial companies and to use public-private partnerships to build a system where all private information about every citizen is also accessible to the police, social workers, security services and Government. The Wellcome Trust, which was involved in the Human Genome Project and was led by Walport for ten years, has produced a plan which involves including a variant file, containing the whole genome of every person minus the reference genome, as an attachment to every medical record in the NHS in England.2 This data would be made available to ‘researchers’ (including commercial companies) for data-mining in the cloud and personalised risk assessments would be returned to individuals. The aim is to transform the NHS in line with proposals developed more than a decade ago by former GlaxoSmithKline Chairman Sir Richard Sykes. This is expected to massively expand the market for medicines, medical tests and other products, such as supplements and cholesterol-lowering margarines, by allowing products to be marketed to individuals based on personal risk assessments, created using statistical analysis of genetic data, medical records and other health information. The proposal to build a DNA database in the NHS was endorsed by the Human Genomics Strategy Group in 20123,4 and the Government (led by Prime Minister David Cameron) has quietly adopted this recommendation without telling members of the public. -
PLK-1 Promotes the Merger of the Parental Genome Into A
RESEARCH ARTICLE PLK-1 promotes the merger of the parental genome into a single nucleus by triggering lamina disassembly Griselda Velez-Aguilera1, Sylvia Nkombo Nkoula1, Batool Ossareh-Nazari1, Jana Link2, Dimitra Paouneskou2, Lucie Van Hove1, Nicolas Joly1, Nicolas Tavernier1, Jean-Marc Verbavatz3, Verena Jantsch2, Lionel Pintard1* 1Programme Equipe Labe´llise´e Ligue Contre le Cancer - Team Cell Cycle & Development - Universite´ de Paris, CNRS, Institut Jacques Monod, Paris, France; 2Department of Chromosome Biology, Max Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria; 3Universite´ de Paris, CNRS, Institut Jacques Monod, Paris, France Abstract Life of sexually reproducing organisms starts with the fusion of the haploid egg and sperm gametes to form the genome of a new diploid organism. Using the newly fertilized Caenorhabditis elegans zygote, we show that the mitotic Polo-like kinase PLK-1 phosphorylates the lamin LMN-1 to promote timely lamina disassembly and subsequent merging of the parental genomes into a single nucleus after mitosis. Expression of non-phosphorylatable versions of LMN- 1, which affect lamina depolymerization during mitosis, is sufficient to prevent the mixing of the parental chromosomes into a single nucleus in daughter cells. Finally, we recapitulate lamina depolymerization by PLK-1 in vitro demonstrating that LMN-1 is a direct PLK-1 target. Our findings indicate that the timely removal of lamin is essential for the merging of parental chromosomes at the beginning of life in C. elegans and possibly also in humans, where a defect in this process might be fatal for embryo development. *For correspondence: [email protected] Introduction Competing interests: The After fertilization, the haploid gametes of the egg and sperm have to come together to form the authors declare that no genome of a new diploid organism. -
Learning Protein Constitutive Motifs from Sequence Data Je´ Roˆ Me Tubiana, Simona Cocco, Re´ Mi Monasson*
TOOLS AND RESOURCES Learning protein constitutive motifs from sequence data Je´ roˆ me Tubiana, Simona Cocco, Re´ mi Monasson* Laboratory of Physics of the Ecole Normale Supe´rieure, CNRS UMR 8023 & PSL Research, Paris, France Abstract Statistical analysis of evolutionary-related protein sequences provides information about their structure, function, and history. We show that Restricted Boltzmann Machines (RBM), designed to learn complex high-dimensional data and their statistical features, can efficiently model protein families from sequence information. We here apply RBM to 20 protein families, and present detailed results for two short protein domains (Kunitz and WW), one long chaperone protein (Hsp70), and synthetic lattice proteins for benchmarking. The features inferred by the RBM are biologically interpretable: they are related to structure (residue-residue tertiary contacts, extended secondary motifs (a-helixes and b-sheets) and intrinsically disordered regions), to function (activity and ligand specificity), or to phylogenetic identity. In addition, we use RBM to design new protein sequences with putative properties by composing and ’turning up’ or ’turning down’ the different modes at will. Our work therefore shows that RBM are versatile and practical tools that can be used to unveil and exploit the genotype–phenotype relationship for protein families. DOI: https://doi.org/10.7554/eLife.39397.001 Introduction In recent years, the sequencing of many organisms’ genomes has led to the collection of a huge number of protein sequences, which are catalogued in databases such as UniProt or PFAM Finn et al., 2014). Sequences that share a common ancestral origin, defining a family (Figure 1A), *For correspondence: are likely to code for proteins with similar functions and structures, providing a unique window into [email protected] the relationship between genotype (sequence content) and phenotype (biological features). -
2019-2020 PO No
HOLY CROSS COLLEGE (AUTONOMOUS) Affiliated to Bharathidasan University Nationally Accredited (3rd Cycle) with 'A' Grade by NAAC College with Potential for Excellence. Tiruchirappalli - 620002. PG DEPARTMENT OF BIOCHEMISTRY Programme: M.Sc. BIOCHEMISTRY 2019-2020 PO No. Programme Outcomes Upon completion of the B.Sc. Degree Programme, the graduate will be able to PO-1 To enable to get quality education in the areas of Biochemistry PO-2 Acquire practical skills to gather information, assess, create and execute new ideas to develop entrepreneurial skills. PO-3 Gain Proficiency in basic laboratory techniques and able to apply the scientific method on lab to land PO-4 Inculcate a domestic and international perspective and be competent enough in the area of life sciences. PO-5 Learn to recognize potential laboratory safety and conserve nature and the environment. PSO No. Programme Specific Outcomes Upon completion of these courses the student would PSO-1 Will use current biochemical and molecular techniques and carry out experiments PSO-2 Monitoring the changes in modern life styles leads to modern diseases PSO-3 Develop skills in cultivation of plants. PSO-4 Prepare them to do higher studies in other biological fields like Genetic, Entomology, Biological Oceanography etc PSO-5 Developed critical thinking skills/laboratory techniques to be capable of designing, carrying out ,interpreting scientific experiments 1 HOLY CROSS COLLEGE (AUTONOMOUS) PG DEPARTMENT OF BIOCHEMISTRY (Students admitted from the year 2018 onwards) M.Sc. Biochemistry-Course -
TOOLS and RESOURCES: a Mammalian Enhancer Trap
1 TOOLS AND RESOURCES: 2 3 A Mammalian Enhancer trap Resource for Discovering and Manipulating Neuronal Cell Types. 4 Running title 5 Cell Type Specific Enhancer Trap in Mouse Brain 6 7 Yasuyuki Shima1, Ken Sugino2, Chris Hempel1,3, Masami Shima1, Praveen Taneja1, James B. 8 Bullis1, Sonam Mehta1,, Carlos Lois4, and Sacha B. Nelson1,5 9 10 1. Department of Biology and National Center for Behavioral Genomics, Brandeis 11 University, Waltham, MA 02454-9110 12 2. Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive 13 Ashburn, VA 20147 14 3. Current address: Galenea Corporation, 50-C Audubon Rd. Wakefield, MA 01880 15 4. California Institute of Technology, Division of Biology and Biological 16 Engineering Beckman Institute MC 139-74 1200 East California Blvd Pasadena CA 17 91125 18 5. Corresponding author 19 1 20 ABSTRACT 21 There is a continuing need for driver strains to enable cell type-specific manipulation in the 22 nervous system. Each cell type expresses a unique set of genes, and recapitulating expression of 23 marker genes by BAC transgenesis or knock-in has generated useful transgenic mouse lines. 24 However since genes are often expressed in many cell types, many of these lines have relatively 25 broad expression patterns. We report an alternative transgenic approach capturing distal 26 enhancers for more focused expression. We identified an enhancer trap probe often producing 27 restricted reporter expression and developed efficient enhancer trap screening with the PiggyBac 28 transposon. We established more than 200 lines and found many lines that label small subsets of 29 neurons in brain substructures, including known and novel cell types. -
A Unicellular Relative of Animals Generates a Layer of Polarized Cells
RESEARCH ARTICLE A unicellular relative of animals generates a layer of polarized cells by actomyosin- dependent cellularization Omaya Dudin1†*, Andrej Ondracka1†, Xavier Grau-Bove´ 1,2, Arthur AB Haraldsen3, Atsushi Toyoda4, Hiroshi Suga5, Jon Bra˚ te3, In˜ aki Ruiz-Trillo1,6,7* 1Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain; 2Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; 3Section for Genetics and Evolutionary Biology (EVOGENE), Department of Biosciences, University of Oslo, Oslo, Norway; 4Department of Genomics and Evolutionary Biology, National Institute of Genetics, Mishima, Japan; 5Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima, Japan; 6Departament de Gene`tica, Microbiologia i Estadı´stica, Universitat de Barcelona, Barcelona, Spain; 7ICREA, Barcelona, Spain Abstract In animals, cellularization of a coenocyte is a specialized form of cytokinesis that results in the formation of a polarized epithelium during early embryonic development. It is characterized by coordinated assembly of an actomyosin network, which drives inward membrane invaginations. However, whether coordinated cellularization driven by membrane invagination exists outside animals is not known. To that end, we investigate cellularization in the ichthyosporean Sphaeroforma arctica, a close unicellular relative of animals. We show that the process of cellularization involves coordinated inward plasma membrane invaginations dependent on an *For correspondence: actomyosin network and reveal the temporal order of its assembly. This leads to the formation of a [email protected] (OD); polarized layer of cells resembling an epithelium. We show that this stage is associated with tightly [email protected] (IR-T) regulated transcriptional activation of genes involved in cell adhesion. -
Evolution of Gene Dosage on the Z-Chromosome of Schistosome
RESEARCH ARTICLE Evolution of gene dosage on the Z-chromosome of schistosome parasites Marion A L Picard1, Celine Cosseau2, Sabrina Ferre´ 3, Thomas Quack4, Christoph G Grevelding4, Yohann Coute´ 3, Beatriz Vicoso1* 1Institute of Science and Technology Austria, Klosterneuburg, Austria; 2University of Perpignan Via Domitia, IHPE UMR 5244, CNRS, IFREMER, University Montpellier, Perpignan, France; 3Universite´ Grenoble Alpes, CEA, Inserm, BIG-BGE, Grenoble, France; 4Institute for Parasitology, Biomedical Research Center Seltersberg, Justus- Liebig-University, Giessen, Germany Abstract XY systems usually show chromosome-wide compensation of X-linked genes, while in many ZW systems, compensation is restricted to a minority of dosage-sensitive genes. Why such differences arose is still unclear. Here, we combine comparative genomics, transcriptomics and proteomics to obtain a complete overview of the evolution of gene dosage on the Z-chromosome of Schistosoma parasites. We compare the Z-chromosome gene content of African (Schistosoma mansoni and S. haematobium) and Asian (S. japonicum) schistosomes and describe lineage-specific evolutionary strata. We use these to assess gene expression evolution following sex-linkage. The resulting patterns suggest a reduction in expression of Z-linked genes in females, combined with upregulation of the Z in both sexes, in line with the first step of Ohno’s classic model of dosage compensation evolution. Quantitative proteomics suggest that post-transcriptional mechanisms do not play a major role in balancing the expression of Z-linked genes. DOI: https://doi.org/10.7554/eLife.35684.001 *For correspondence: [email protected] Introduction In species with separate sexes, genetic sex determination is often present in the form of differenti- Competing interests: The ated sex chromosomes (Bachtrog et al., 2014). -
Global Cellular Response to Chemotherapy- Induced
RESEARCH ARTICLE elife.elifesciences.org Global cellular response to chemotherapy- induced apoptosis Arun P Wiita1,2, Etay Ziv3,4, Paul J Wiita5, Anatoly Urisman1,6, Olivier Julien1, Alma L Burlingame1, Jonathan S Weissman3,7, James A Wells1,3* 1Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States; 2Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States; 3Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; 4Department of Radiology, University of California, San Francisco, San Francisco, United States; 5Department of Physics, The College of New Jersey, Ewing, United States; 6Department of Pathology, University of California, San Francisco, San Francisco, United States; 7Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States Abstract How cancer cells globally struggle with a chemotherapeutic insult before succumbing to apoptosis is largely unknown. Here we use an integrated systems-level examination of transcription, translation, and proteolysis to understand these events central to cancer treatment. As a model we study myeloma cells exposed to the proteasome inhibitor bortezomib, a first-line therapy. Despite robust transcriptional changes, unbiased quantitative proteomics detects production of only a few critical anti-apoptotic proteins against a background of general translation inhibition. Simultaneous ribosome profiling further reveals potential translational regulation of stress response genes. Once the apoptotic machinery is engaged, degradation by caspases is largely independent of upstream bortezomib effects. Moreover, previously uncharacterized non-caspase proteolytic events also participate in cellular deconstruction. Our systems-level data also support co-targeting the anti-apoptotic regulator HSF1 to promote cell death by bortezomib. -
Wellcome Trust Annual Report and Financial Statements 2019 Is © the Wellcome Trust and Is Licensed Under Creative Commons Attribution 2.0 UK
Annual Report and Financial Statements 2019 Table of contents Report from Chair 3 Report from Director 5 Trustee’s Report 7 What we do 8 Review of Charitable Activities 9 Review of Investment Activities 21 Financial Review 31 Structure and Governance 36 Social Responsibility 40 Risk Management 42 Remuneration Report 44 Remuneration Committee Report 46 Nomination Committee Report 47 Investment Committee Report 48 Audit and Risk Committee Report 49 Independent Auditor’s Report 52 Financial Statements 61 Consolidated Statement of Financial Activities 62 Consolidated Balance Sheet 63 Statement of Financial Activities of the Trust 64 Balance Sheet of the Trust 65 Consolidated Cash Flow Statement 66 Notes to the Financial Statements 67 Alternative Performance Measures and Key Performance Indicators 114 Glossary of Terms 115 Reference and Administrative Details 116 Table of Contents Wellcome Trust Annual Report 2019 | 2 Report from Chair During my tenure at Wellcome, which ends in The macro environment is increasingly challenging, 2020, I count myself lucky to have had the which has created volatility in financial markets. opportunity to meet inspiring people from a rich Q4 2018 was a very difficult quarter, but the diversity of sectors, backgrounds, specialisms resumption of interest rate cuts by the US Federal and scientific fields. Reserve underpinned another year of gains for our portfolio. We recognise that the cycle is extended, Wellcome’s achievements belong to the people and that the portfolio is likely to face more who work here and to the people we fund – it is challenging times ahead. a partnership that continues to grow stronger, more influential and more ambitious, spurred by The team is working hard to ensure that our independence. -
OVER £140 Prime Minister, the Rt Hon David Came
PRIME MINISTER QUARTERLY INFORMATION: 1 APRIL – 30 JUNE 2011 GIFTS (RECEIVED) OVER £140 Prime Minister, The Rt Hon David Cameron MP Date gift From Gift Value Outcome received April 2011 Prime Minister of Furniture Over Held by Department Pakistan limit April 2011 Prime Minister of Rug Over Held by BHC Pakistan limit Islamabad April 2011 Italian Aeronautica Leather jacket Over Held by Department Militare limit April 2011 Portmeirion Potteries China Over Held by Department Group limit May 2011 President Obama and Silver jewellery and Over Held by Department Mrs Obama First Edition Book limit May 2011 President of Russia Painting Over Held by Department limit May 2011 President of France Pen Set and Over Held by Department Glassware limit June 2011 Prime Minister of Picture Over Held by Department Malaysia limit GIFTS (GIVEN) OVER £140 Prime Minister, The Rt Hon David Cameron MP Date gift From Gift Value Outcome given Nil return HOSPITALITY1 Prime Minister, The Rt Hon David Cameron MP Date Name of Organisation Type of Hospitality Received NIL RETURN 1 Does not normally include attendance at functions hosted by HM Government; ‘diplomatic’ functions in the UK or abroad, hosted by overseas governments; minor refreshments at meetings, receptions, conferences, and seminars; and offers of hospitality which were declined. OVERSEAS TRAVEL Prime Minister Date(s) of trip Destination Purpose of ‘No 32 (The Number of Total cost trip Royal) officials including travel Squadron’ accompanying and or ‘other Minister, where accommodation of RAF’ or non-scheduled -
Understanding the an English Agribusiness Lobby Group
Understanding the NFU an English Agribusiness Lobby Group Ethical Consumer Research Association December 2016 Understanding the NFU - an English Agribusiness Lobby-group ECRA December 2016 1 Contents 1. Introduction – The NFU an English Agribusiness Lobby group 3 2. Economic Lobbying – undermining the smaller farmer 2.1 NFU and farm subsidies – promoting agribusiness at the expense of smaller farmers 11 2.2 NFU and TTIP – favouring free trade at the expense of smaller farms 15 2.3 NFU and supermarkets – siding with retailers and opposing the GCA 17 2.4 NFU and foot and mouth disease – exports prioritised over smaller producers 20 3. Environmental Lobbying – unconcerned about sustainability 3.1 NFU, bees and neonicotinoids – risking it all for a few pence more per acre 24 3.2 NFU and soil erosion – opposing formal protection 28 3.3 NFU and air pollution – opposing EU regulation 31 3.4 NFU, biodiversity and meadows – keeping the regulations away 33 3.5 NFU and Europe – keeping sustainability out of the CAP 41 3/6 NFU and climate change – a mixed response 47 3.7 NFU and flooding – not listening to the experts? 51 4. Animal interventions – keeping protection to a minimum 4.1 Farm animal welfare – favouring the megafarm 53 4.2 NFU, badgers and bovine TB – driving a cull in the face of scientific evidence 60 4.3 The Red Tractor label – keeping standards low 74 5. Social Lobbying – passing costs on to the rest of us 5.1 NFU and Organophosphates in sheep dip – failing to protect farmers’ health 78 5.2 NFU and road safety – opposing regulations 82 5.3 NFU and workers’ rights – opposing the Agricultural Wages Board 86 5.4 NFU and Biotechnology – Supporting GM crops 89 6. -
Strategische Und Operative Handlungsoptionen Für Wissenschaftliche Einrichtungen Zur Gestaltung Der Open-Access-Transformation
! ! ! !"#$"%&'()*%+,-.+/0%#$"'1%+2$-.3,-&(/0"'/-%-+ 45#+6'((%-()*$4"3')*%+7'-#')*",-&%-+8,#+ 9%("$3",-&+.%#+:0%-;<))%((;=#$-(4/#>$"'/-+ ! "#$$%&'('#)*! "#$!%$&'()#()!*+,!'-'*+./,01+(!2$'*+,! ")+')&!,-#.)$),-#(%! /"&0!,-#.01! ! +/()+$+/013! '(!*+$!41/&5,561/,01+(!7'-#&383! *+$!9#.:5&*3;<(/=+$,/383!"#!>+$&/(! ! =5(!9+/("!4'.6+&! ! ! ?/+!4$8,/*+(3/(!*+$!9#.:5&*3;<(/=+$,/383!"#!>+$&/(@!! 4$5AB!?$B;C()B!?$B!D':/(+!E#(,3! ! ?/+!?+-'(/(!*+$!41/&5,561/,01+(!7'-#&383@! 4$5AB!?$B!2':$/+&+!F+3"&+$! ! ! 2#3'013+$! %$,3)#3'013+$@!! ! 4$5AB!?$B!4+3+$!D01/$.:'01+$! GH+/3)#3'013+$@!! 4$5AB!?$B!I5&A$'.!95$,3.'((! ! ?'3#.!*+$!?/,6#3'3/5(@!JKB!F'/!LMLJ! !"#$%&'()*+),-#",'. G#,'..+(A',,#()!BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB!NC! O:,3$'03!BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB!NCC! ?'(-,')#()!BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB!NCCC! O:-P$"#(),=+$"+/01(/,!BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB!CQ! R':+&&+(=+$"+/01(/,!BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB!QCC! O::/&*#(),=+$"+/01(/,!BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB!QCCC!