Bringing Elife to Life | Mark Patterson
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Stem Strategy
SUCCESS THROUGH STEM STEM STRATEGY In response to the ‘Report of the STEM Review’ HELPING TO EMPOWER FUTURE GENERATIONS THROUGH SCIENCE, TECHNOLOGY, ENGINEERING AND MATHEMATICS TO GROW A DYNAMIC, INNOVATIVE ECONOMY 2011 CONTENTS 1. INTRODUCTION 4 2. CONTEXT 5 3. THE ROLE OF THE DEMAND SIDE 8 4. THE ROLE OF THE SUPPLY SIDE 10 5. RECOMMENDATIONS FOR ACTION 15 6. STRUCTURES FOR IMPLEMENTATION 23 7. CONCLUSION AND PRIORITY ACTIONS 25 ANNEX A – Existing Government STEM Activity ANNEX B – Government STEM Action Plan 1. INTRODUCTION Commissioned by the Department for Employment The Report contains 20 recommendations grouped and Learning (DEL) and the Department of Education under four ‘imperatives’. (DE), the review of Science, Technology, Engineering • Imperative 1 - Business must take the lead and Mathematics (STEM) commenced formally on in promoting STEM. 29 June 2007. Chaired by Dr Hugh Cormican, founder and former Chief Executive of Andor Technologies • Imperative 2 - The key constraints in the STEM Ltd., the steering group comprised representatives artery must be alleviated. from business, government and academia and the Programme Manager for the review was Dr Alan Blair, • Imperative 3 - There needs to be increased from the Association of NI Colleges (now Colleges NI). flexibility in the provision of STEM education. Three working groups reported to the steering group, • Imperative 4 - Government must better each of which was responsible for taking forward a coordinate its support for STEM. key strand of the Review. These working groups ensured This STEM Strategy forms Government’s response a focus on the respective roles of business, education, to the ‘Report of the STEM Review’. -
Jeremy Farrar
FEATURE The BMJ THE BMJ INTERVIEW BMJ: first published as 10.1136/bmj.n459 on 19 February 2021. Downloaded from [email protected] Cite this as: BMJ 2021;372:n459 http://dx.doi.org/10.1136/bmj.n459 Jeremy Farrar: Make vaccine available to other countries as soon as Published: 19 February 2021 our most vulnerable people have received it The SAGE adviser and Wellcome Trust director tells Mun-Keat Looi how the UK government acted too slowly against the pandemic, about the perils of vaccine nationalism, and why he is bullish about controlling covid variants Mun-Keat Looi international features editor “Once the UK has vaccinated our most vulnerable among healthcare workers. We had no human communities and healthcare workers we should make immunity, no diagnostics, no treatment, and no vaccines available to other countries,” insists the vaccines. infectious disease expert Jeremy Farrar. This could Every country should have acted then. Singapore, avert further public health and economic disaster, China, and South Korea did. Yet most of Europe and he says, describing it as “enlightened self-interest, North America waited until the middle of March, and as well as the right ethical thing to do.” that defined the first wave. Countries including the In April 2020, soon after the first UK lockdown began, UK were unwilling to act early, before they felt Farrar predicted that the UK would have one of the comfortable; were unwilling to go deeper than they worst covid-19 death rates in Europe. As a member thought they had to; and were unwilling to keep of the Scientific Advisory Group for Emergencies restrictions in place for as long as was needed. -
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). -
Evidence Synthesis on the EU-UK Relationship on Research and Innovation January 2018
Evidence synthesis on the EU-UK relationship on research and innovation January 2018 1. Introduction The Royal Society and the Wellcome Trust have undertaken a rapid evidence synthesis on the EU-UK research and innovation relationship as part of their Future Partnership Project. Organisations and individuals were invited to submit evidence and analyses for inclusion. Evidence was also gathered through internet searches to ensure an inclusive approach. The Annex is a summary of the methods. Two questions were used in gathering evidence and in determining the material in scope: 1. What incentives, infrastructure and mechanisms can be accessed by research and innovation organisations, funders and individuals in Member States to support collaborations? 2. How do Member States currently use and benefit from these and how might they be affected by Brexit? This paper is a synthesis of the evidence and covers funding, infrastructures, mobility, collaboration and regulation, with a focus on links between the EU and the UK. 2. Overview of the evidence base A few major reports were of particular relevance; the Royal Society’s three reports on the role of the EU in UK research and innovation and two reports commissioned from Technopolis Group by UK organisations, on the role of EU funding in UK research and innovation and the impact of collaboration: the value of UK medical research to EU science and health1,2. These documents were often referenced in other submissions. A report from the Lords Science and Technology Committee’s inquiry on EU Membership and UK Science also summarises many sources of evidence relevant to this synthesis. -
Janet Thornton / 19 July 2018
Oral History: Janet Thornton / 19 July 2018 DISCLAIMER The information contained in this transcript is a textual representation of the recoded interview which took place on 2018-07-19 as part of the Oral Histories programme of the EMBL Archive. It is an unedited, verbatim transcript of this recorded interview. This transcript is made available by the EMBL Archive for free reuse for research and personal purposes, providing they are suitably referenced. Please contact the EMBL Archive ([email protected]) for further information and if you are interested in using material for publication purposes. Some information contained herein may be work product of the interviewee and/or private conversation among participants. The views expressed herein are solely those of the interviewee in his private capacity and do not necessary reflect the views of the EMBL. EMBL reserves the right not to be responsible for the topicality, accuracy, completeness or quality of the information provided. Liability claims regarding damage caused by the use of any information provided, including any kind of information which is incomplete or incorrect, will therefore be rejected. 2 2018_07_19_JanetThornton Key MG: Mark Green, former head of Administration at EMBL-EBI JT: Participant, Janet Thornton, former Director of EMBL-EBI and current EMBL-EBI Research Group Leader [??? At XX:XX] = inaudible word or section at this time MG: My name is Mark Green. This is Thursday 19th July 2018 and I’m in the Pompeian Room in Hinxton Hall on the Wellcome Genome Campus where EMBL-EBI is based and I’m about to do an interview as part of the oral histories programme of the EMBL Archive, with Janet Thornton, and I’d just like to ask Janet to introduce herself and to say a bit about her life before EMBL. -
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. -
Francis Crick Institute-CS-JB080719.Indd
The Francis Crick Institute THE FRANCIS CRICK INSTITUTE The Crick is a landmark partnership between three of the UK’s largest funders of biomedical research: the Medical Research Council, Cancer Research UK and the Wellcome Trust, and three of its leading universities: UCL, Imperial College London and King’s College London. This represents an unprecedented joining of forces to tackle major scientific problems and generate solutions to the emerging health challenges of the 21st century. Business Challenge: The VIRTUS Solution: The Crick is being built in central London, where space is at a Collaboration is at the heart of the Crick’s vision. Its work premium. It was decided, early in the planning process, that will help to understand why disease develops and to find most of the Crick’s data would need to be stored off-site. new ways to diagnose, prevent and treat a range of illnesses However, the institute realised there were major benefits to – such as cancer, heart disease and stroke, infections and sharing resources with other institutions, particularly in terms neurodegenerative diseases. The Crick will bring together of scientific analysis. As the Crick’s plans developed, a number outstanding scientists from all disciplines, carrying out research of institutions – both within the original partners and more that will help improve the health and quality of people’s lives, broadly - had similar requirements and identified the same and keeping the UK at the forefront of medical innovation. potential for collaboration in having a colocated shared data centre. “The Crick has been proud to take a leading role in support of Janet. -
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. -
Diversification of the Caenorhabditis Heat Shock Response by Helitron Transposable Elements Jacob M Garrigues, Brian V Tsu, Matthew D Daugherty, Amy E Pasquinelli*
RESEARCH ARTICLE Diversification of the Caenorhabditis heat shock response by Helitron transposable elements Jacob M Garrigues, Brian V Tsu, Matthew D Daugherty, Amy E Pasquinelli* Division of Biology, University of California, San Diego, San Diego, United States Abstract Heat Shock Factor 1 (HSF-1) is a key regulator of the heat shock response (HSR). Upon heat shock, HSF-1 binds well-conserved motifs, called Heat Shock Elements (HSEs), and drives expression of genes important for cellular protection during this stress. Remarkably, we found that substantial numbers of HSEs in multiple Caenorhabditis species reside within Helitrons, a type of DNA transposon. Consistent with Helitron-embedded HSEs being functional, upon heat shock they display increased HSF-1 and RNA polymerase II occupancy and up-regulation of nearby genes in C. elegans. Interestingly, we found that different genes appear to be incorporated into the HSR by species-specific Helitron insertions in C. elegans and C. briggsae and by strain-specific insertions among different wild isolates of C. elegans. Our studies uncover previously unidentified targets of HSF-1 and show that Helitron insertions are responsible for rewiring and diversifying the Caenorhabditis HSR. Introduction Heat Shock Factor 1 (HSF-1) is a highly conserved transcription factor that serves as a key regulator of the heat shock response (HSR) (Vihervaara et al., 2018). In response to elevated temperatures, HSF-1 binds well-conserved motifs, termed heat shock elements (HSEs), and drives the transcription *For correspondence: of genes important for mitigating the proteotoxic effects of heat stress. For example, HSF-1 pro- [email protected] motes the expression of heat-shock proteins (HSPs) that act as chaperones to prevent HS-induced misfolding and aggregation of proteins (Vihervaara et al., 2018).