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Wcb Brochure 2019.Pdf 2019 Wellcome Centre for Cell Biology 2019 Title Historical Background A Content Text The expansion of research in cell biology Director’s Report 04 was planned in 1992 as a result of the Robin Allshire 06 vision of Professor Sir Kenneth Murray, A. Jeyaprakash Arulanandam 08 who was at the time Biogen Professor at the Institute of Cell and Molecular Jean Beggs 10 Biology. A seed contribution of £2.5 Adrian Bird 12 million from the Darwin Trust was Dhanya Cheerambathur 14 followed by financial commitments from The Wolfson Foundation, the University Atlanta Cook 16 and the Wellcome Trust, allowing Bill Earnshaw 18 construction of the Michael Swann Patrick Heun 20 Building. The majority of research space Tony Ly 22 was earmarked for Wellcome Trust- funded research. Recruitment, based on Adele Marston 24 research excellence at all levels in the Dónal O'Carroll 26 area of cell biology, began in earnest in Hiro Ohkura 28 1993, mostly but not exclusively, through Juri Rappsilber 30 the award of Research Fellowships from the Wellcome Trust. The Swann Building Kenneth E Sawin 32 was first occupied by new arrivals A. Legends Eric Schirmer 34 in January 1996 and became “The David Tollervey 36 Wellcome Trust Centre for Cell Biology” Philipp Voigt 38 from October 2001. Core funding for the Centre from the Wellcome Trust was Malcolm Walkinshaw 40 renewed in 2006, 2011 and 2016. Julie Welburn 42 Selected Publications: Marcus D Wilson 44 text Public Engagement 46 List of Groups 48 Centre Publications 2017 - 2019 54 International Scientific Advisory Board 60 2 3 Director’s Report The Wellcome Centre for Cell Biology (WCB) is one of fifteen UK-based, Wellcome-funded research centres. The WCB WCB prides itself on the diversity of our members, but there is always room for improvement. To this end, a Centre Diversity and research groups, and our associated research facilities, occupy the Michael Swann Building on the King’s Buildings Campus Inclusion Group has been established during the past year, to identify areas for improvement and disseminate good practice. of the University of Edinburgh. Constructed in the mid 1990s, the Swann Building was designed as a centre for research in Centre staff have also delivered an outstanding programme of public engagement; my thanks go to everyone who gave up their molecular cell biology. time and brought their enthusiasm to share our work with the broader community in Edinburgh. We have now established an advisory board for public engagement and were awarded a Wellcome Research Enrichment Award – Public Engagement, to The key goal of the WCB is to gain new insights into cell structure and function at levels from molecular interactions to complex help us deliver our strategy. systems. The many biochemical reactions taking place within cells form pathways that are highly organised; physically, in space and in time. Our work advances understanding of these pathways by bringing together the major themes of nuclear A substantial feature of life in WCB over the past year has been the major building project “Building a New Biology” aimed at organisation, genome packaging and transmission, chromatin states and RNA biology. This brochure presents a very brief transforming the adjacent buildings into a state-of-the-art research hub. I thank all of my colleagues for their tolerance and overview of our research and highlights some of the exciting results obtained during the past year. I am delighted that the forbearance during the disruption caused by this important work. WCB has again made excellent progress with every group reporting innovative, world-class research, as reflected in our many Let me end by reiterating my deepest thanks to all of our talented, dedicated researchers and support staff and congratulate notable publications. them again on their excellent work over the year. I would like to take this opportunity to welcome three new research groups, led by Dhanya Cheerambathur, Marcus Wilson and Dónal O’Carroll, who joined WCB during 2018. Dhanya Cheerambathur is a Wellcome Sir Henry Dale Fellow, studying cytoskeletal assembly and dynamics during neuronal development. Marcus Wilson is also a Wellcome Sir Henry Dale Fellow, David Tollervey studying mechanisms of epigenetic modifications. Finally, Prof. Dónal O’Carroll is Wellcome Senior Investigator, studying RNA function in germ and stem cell biology. These outstanding researchers will bring dynamic research projects and fresh approaches to WCB. I am also very pleased to congratulate several WCB group leaders on prestigious awards received in 2018: Jean Beggs received the RNA Society Lifetime Achievement Award, the premier recognition in the field of RNA biology; Dónal O’Carroll was elected as a Fellow of the Royal Society of Edinburgh, which is the national academy for Scotland; Adrian Bird received the Buchanan Medal of the Royal Society for distinguished contributions to the biomedical sciences. Julie Welburn received an EMBO Young Investigator award, joining an elite group of up-and-coming European biologists; Dhanya Cheerambathur received the Wellcome Beit Prize, awarded to outstanding biomedical researchers who have been awarded other Wellcome fellowships. We are proud to be associated with colleagues who merit these significant indicators of esteem. We are keen for the insights and technologies that emerge from the cutting-edge research in WCB be used for the wider good. To facilitate this, we have established interactions with the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), a centre of research excellence established in Accra, Ghana. During the coming year, WCB staff will be delivering teaching workshops in WACCBIP working to develop co-applications for funding which are expected to form the basis for future productive collaborations. In tackling complex biological questions and problems, the importance of interdisciplinary approaches is increasingly evident. Despite this, most students operate within a single unit, often with only limited direct contact with researchers from other fields. In an effort to address this issue, we have established a pilot, cross-disciplinary PhD programme; “Integrative Cell Mechanisms”, in partnership with physical and data science experts across Edinburgh. PhD students on the programme will each have two supervisors; one with a “biological” background and the other with expertise in data analysis or a physical science. 4 5 Epigenetic inheritance: establishment and transmission of A specialized chromatin domains Chromosomal DNA is wrapped around nucleosomes containing core histones (H3/H4/H2A/ H2B). However, at centromeres a specific histone H3 variant, CENP-A, replaces histone H3 to form specialized CENP-A nucleosomes. CENP-A chromatin is critical for assembly of the chromosome segregation machinery – kinetochores – at these specific chromosomal locations and is flanked by histone H3 lysine 9 methylated heterochromatin. Robin Allshire Our goal is to decipher conserved mechanisms that establish, maintain and regulate the B assembly of heterochromatin and CENP-A chromatin domains. Heterochromatin is required for the establishment of CENP-A chromatin on centromere DNA. One objective is to provide further Co-workers: insight into mechanisms that promote heterochromatin formation on pericentromeric repeats. Tatsiana Auchynnikava Heterochromatin might also silence genes throughout the genome; we therefore also investigate how heterochromatin formation is regulated and whether such mechanisms influence phenotype. Roberta Carloni We endeavour to determine how heterochromatin, spatial nuclear organisation and non-coding Tadhg Devlin RNAPII transcription combine to mediate CENP-A incorporation at centromeres. Luke Eivers Our main questions are: C Andreas Fellas 1. How do DNA, RNA and chromatin signatures instigate the assembly of specialized chromatin domains? Nitobe London 2. How does chromatin architecture and subnuclear compartmentalization affect specialized Sunil Nahata chromatin domains? 3. How does heterochromatin influence gene expression? Alison Pidoux 2 2 A combination of next-generation sequencing technologies allowed the de novo assembly of the Desislava Staneva 2 genomes of two fission yeast species that are evolutionarily distinct from Schizosaccharomyces Manu Shukla pombe. Our assemblies are contiguous across all three centromeres, and other heterochromatin A. Centromere organisation is conserved, sequence is not. CENP-A chromatin (Purple) and H3K9me2 heterochromatin (Orange) domains Puneet Singh regions, of both species and permits comparison of centromere organization between these mapped by ChIP-seq to new assemblies of S. octosporus and S. cryophilus centromere 3 (Tong, Pidoux et al. Nat. Comm. in press). divergent species (Figure A). Centromeres from all three species retain an overall structural B. ChIP analysis on synchronized cells shows that, similar to endogenous centromeres (green), H3 levels increase on ectopic centromeric Pin Tong resemblance, however, no sequence similarity is detected between repetitive elements and cc2 (red) DNA during S phase and decline in G2. Septation peak is coincident with S phase (Shukla et al. 2018). Jesus Torres-Garcia central regions of even the closest two species. C. ChIP for replacement of old H3 with newly synthesized T7-tagged H3 shows that H3 nucleosomes are turned over on ectopic centromeric cc2 DNA at a high rate during G2 (Shukla et al. 2018). Gabor Varga Interspecies functional tests reveal that non-homologous S. octosporus and
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