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The Wellcome Trust/Cancer Research UK Gurdon Institute 2015 PROSPECTUS / ANNUAL REPORT 2014 Gurdon INSTITUTE PROSPECTUS 2015 ANNUAL REPORT 2014 http://www.gurdon.cam.ac.uk CONTENTS THE INSTITUTE IN 2014 INTRODUCTION THE INSTITUTE IN 2014 INTRODUCTION........................................................................................................................................3 HISTORICAL BACKGROUND..........................................................................................................4 CENTRAL SUPPORT SERVICES....................................................................................................4 FUNDING.........................................................................................................................................................4 ENERGY AND ENVIRONMENT..........................................................................................................5 PUBLIC ENGAGEMENT..........................................................................................................5 POST-DOC ASSOCIATION..........................................................................................................5 RETREAT............................................................................................................................................................5 RESEARCH GROUPS.........................................................................................................6 MEMBERS OF THE INSTITUTE................................................................................42 CATEGORIES OF APPOINTMENT..............................................................................42 POSTGRADUATE OPPORTUNITIES..........................................................................42 SENIOR GROUP LEADERS.............................................................................................42 GROUP LEADERS.......................................................................................................................46 VISITING STUDENTS AND RESEARCHERS....................................................................47 ADMINISTRATION/SUPPORT STAFF........................................................48 INSTITUTE PUBLICATIONS.......................................................................................50 TALKS BY INSTITUTE RESEARCHERS.............................................................55 GURDON INSTITUTE SEMINAR SERIES..........................................................58 OTHER INFORMATION STAFF AFFILIATIONS.............................................................................................................58 HONOURS AND AWARDS........................................................................................................59 EDITORIAL BOARDS OF JOURNALS.............................................................................59 INTERNATIONAL SCIENTIFIC ADVISORY BOARD...........................................59 CHAIRMAN OF MANAGEMENT COMMITTEE................................................59 LEAVERS DURING 2014................................................................................................60 ACKNOWLEDGEMENTS..............................................................Inside back cover 2 THE GURDON INSTITUTE Much of our activity this year has been devoted to investigating ways that the Gurdon Institute can expand to provide extra space for new research directions. This effort has been stimulated in part by Tony Kouzarides’ sterling efforts to stimulate translational research in the University by setting up a Therapeutics Centre as a platform for collaborations between Cambridge academics and pharmaceutical companies. As our research develops into novel areas, we also need more room for new facilities, such as super-resolution imaging, genomics and tissue culture space for longterm organoid experiments. After much discussion and a generous offer of financial support from Dr Jonathan Milner, a former member of the Institute, the University has agreed to house the Therapeutics Centre within a new building on the Cambridge Biomedical campus. We are delighted that this new Centre will give a boost to translational research within the University, as this has long been an area where the Gurdon Institute has excelled. This was exemplified this year by the approval throughout Europe and the USA of the ovarian cancer treatment Lynparza/Olaparib, a drug initially developed by KuDOS, a start-up company founded by Steve Jackson. Although the Therapeutic Centre will be based on the Addenbrooke’s site, the Gurdon Institute will remain in the centre of town, where we hope to build an extension to meet our other needs. Designing and raising the funds for this venture will be a major goal for 2015. The research in the Institute continues to flourish, and the outstanding work of my colleagues was recognised with several prizes and awards last year. Azim Surani was awarded a Jawaharlal Nehru Science Fellowship by the Indian government to spend a year at the Institute for Stem Cell Biology and Regenerative Medicine in Bangalore and also won the International Society for Stem Cell Research McEwen Award for innovation; John Gurdon was elected an honorary member of the Royal College of Physicians, and received the Mike Hogg Award from the MD Anderson Cancer Centre, Houston, Texas and an honorary degree from Rockefeller University; Andrea Brand was made an honorary fellow of Brasenose College, University of Oxford; Ben Simons was awarded the Franklin Medal and Prize by the Institute of Physics; Steve Jackson was elected a Fellow of the European Academy of Cancer Sciences and the Imperial College Faculty of Medicine, and won the GSK Discovery Fast Track Challenge with Dr. Delphine Larrieu; Meritxell Huch won the National Centre for Replacement, Refinement and Reduction of Animals in Research (3Rs) Prize for developing a method to grow mini-livers from adult stem cells; Phil Zegerman was selected to join the EMBO Young Investigator programme for the best young group leaders in Europe; Julie Ahringer and Nick Brown were both awarded Professorships by the University, and Rick Livesey was promoted to Senior Group Leader within the Gurdon Institute. Finally, the Gurdon Institute received an Athena Swan Bronze Award “to recognise and celebrate good practice in recruiting, retaining and promoting women in SET within Higher Education.” Thanks are due to Julie Ahringer, Suzanne Campbell, Ann Cartwright, Di Foster, Annabel Griffiths, Jon Pines and Emmanuelle Vire on the Equality and Diversity committee for their hard work in putting the application together and identifying ways to improve the working environment for women in the Institute. It was not just the group leaders who received awards this year and I would like to commend Josep Foment (a postdoc in the Jackson group), Laura Wagstaff (a postdoc in the Piddini group) and Helen Fox (a graduate student with Jenny Gallop) for winning prizes for the posters they presented at conferences. I would also like to congratulate two former members of the Institute: Ron Laskey (one of the founders of the Institute) received a Cancer Research UK Lifetime Achievement Award for “Challenging nuclear fiction: new roles for old nuclear proteins” and Sophie Martin (a former PhD student in the St Johnston group, now a Professor at the University of Lausanne) won the EMBO Gold Medal for “her research to understand the organization and development of the cell”. All of the research within the Institute depends on external grants, and group leaders have been very successful at competing for funding this year. Andrea Brand and Eric Miska have both received Wellcome Trust Senior Investigator Awards to study “the nutritional control of neural stem-cell quiescence and reactivation” and “transgenerational epigenetic inheritance: adaptation, genome stability and evolution” respectively. Meritxell Huch, who joined us in January, was awarded a Henry Dale Fellowship to investigate the mechanisms of adult liver regeneration and also won a Wellcome Trust Beit Prize Fellowship, which is given to the best researchers at the beginning of their independent careers. Group leaders also secured a number of other grants, including BBSRC grants to Andrea Brand and Nick Brown. Most notably, Rick Livesey and his collaborators at the Institute of Neurology (UCL) received an award of £2 million from Alzheimer’s Research UK and the Alborada Trust to establish the Alzheimer’s Research UK Stem Cell Research Centre, which was announced by the Prime Minister in June at the G8 Dementia summit. Under the excellent leadership of Dr Emmanuelle Vire, the Gurdon Institute Postdoc Association (GIPA) has been playing an increasingly important role in the life of the Institute. The past year was a particularly active one for GIPA: it organised a one day symposium on “Building an organism” with talks from Thomas Graf (CGR Barcelona), Greg Hannon (Cold Spring Harbor Laboratory), Ewa Paluch (University College London) and Jan-Michel Peters (IMP Vienna) and also hosted research seminars from Susan Strome (University of California Santa Cruz), Andrew Jackson (University of Edinburgh), Philippe Pasero (CNRS, Montpellier), Thijn Brummelkamp (NCI, Amsterdam), Peter Campbell (The Sanger Institute) and Jonathan Whetstine (Harvard Medical School, Boston). In addition, GIPA organised six career pathways talks, in which former Gurdon Institute postdocs described their careers outside academia. The highlight of the postdoc calendar is the annual retreat and barbecue, which focused this time on promoting new collaborations, with a speed-dating session that used an algorithm developed by Rafael Carazo-Salas to pair up postdocs with different research topics and expertise. This year also saw the launch of an innovative postdoc mentoring programme, in which senior postdocs mentor new postdocs and PhD students to help them settle into to Cambridge and the Institute. THE GURDON INSTITUTE 3 THE INSTITUTE IN 2014 Another person who deserves special mention this year is Hélène Doerflinger, who does a fantastic job organising the Institute’s outreach activities. Hélène launched the “Mobile Laboratory” this year, with equipment funded by the Wellcome Trust Institutional Strategic Support Fund. The Mobile Laboratory made four school visits in 2014, with a team of Gurdon scientists going into local primary school classes to give year 5 and 6 children the chance to discover biology using real lab equipment. Our outreach activities also cater for secondary school students, with six groups of sixth-form students visiting the Gurdon Institute for two hour workshops on “Cell division and cancer”, and fifteen students spending one week shadowing an Institute postdoc or student to gain an insight into working in a research laboratory. The highlight of the year was European Researchers’ Night at the Natural History Museum in London that was attended by 30,000 members of the public, at which Institute members ran a stand explaining “What flies can tell us about human health”. THE INSTITUTE IN 2014 The Institute is an integrated part of Cambridge University, and all group leaders are also members of another University department within the School of Biological Sciences, and contribute to both undergraduate and graduate student teaching. The University has also been generous in its support of the Institute, particularly through various student and Herchel Smith schemes, and its funding of equipment. PUBLIC ENGAGEMENT CENTRAL SUPPORT SERVICES In 2014, the Gurdon Institute has undertaken many Public Engagement activities for different audiences. With The Mobile Lab project, a team of scientists ‘took a lab into local primary schools’ and ran a workshop using microscopes. We organised workshops for sixth-form students to give them the opportunity to visit the Institute and meet scientists. We welcomed sixth-form students in our labs for work experience. We participated in the Cambridge Alumni Festival. We organised core talks aimed at our nonscientist colleagues. We took part in the European Researchers’ Night at the Natural History Museum, London. The Institute’s ‘core staff ’ provides essential administrative, technical and computing support to our scientists so that the scientists can spend as much time as possible on their research. The success of the Institute depends on all our core staff who do excellent jobs supporting our research and keeping everything running smoothly. It also depends on our great esprit de corps, I would like to thank the many people who arrange various events during the year, particularly Ann Cartwright, Suzanne Campbell, Emma Rawlins and Phil Zegerman for organising the Institute retreat, the second-year PhD students for running the weekly Happy Hours and the retreat treasure hunt, and the Social Committee for parties. Finally, I am particularly grateful to Robb Krumlauf and the rest of our International Scientific Advisory Board, who visited us for two days in March to give us their usual dose of excellent advice and support. GURDON INSTITUTE POST-DOC ASSOCIATION Grant income 1992 - 2014 Total number of staff (December 2014) HISTORICAL BACKGROUND The Institute was founded in 1989 to promote research in the areas of developmental biology and cancer biology, and is situated in the middle of the area containing the biological science departments of the University of Cambridge, close to the newly-established Wellcome Trust Institute for Stem Cell Research. The Institute hosts a number of independent research groups in a purpose-built building designed to promote as much interaction as possible. Developmental and cancer biology are complementary since developmental biology is concerned with how cells, including stem cells, acquire and maintain their normal function, whereas cancer is a result of a cell breaking loose from its correct controls and becoming abnormal. Both areas require a detailed knowledge of intra- and intercellular processes, which need to be analysed at the scientific and technical levels. To understand what goes wrong when a cell becomes cancerous requires knowledge of the processes that ensure correct function in normal development. At the technical level, the analysis of cellular and molecular processes requires familiarity with techniques that no single person can master, including molecular biology, biochemistry, microarray technology, bioinformatics, cell culture, imaging and embryonic manipulations. There is, therefore, a major benefit in having scientists with different but complementary knowledge and technical skills working in close proximity to one another as is the case in the Institute. 4 THE GURDON INSTITUTE to boiling enough water to make 80 million cups of tea! We continue to engage with the wider University community who wish to learn from our achievements. FUNDING Our two major funding bodies, the Wellcome Trust and Cancer Research UK, continue to offer the Institute vital backing in the form of Fellowships, individual programme, project and equipment grants, in addition to our invaluable core funding. Other sources of funding, both direct and indirect, include the European Commission, BBSRC, MRC, the Royal Society, NIH, the European Molecular Biology Organization, HFSP, the Isaac Newton Trust, Alzheimer’s Research UK, the Japan Society for the Promotion of Science, the March of Dimes, the Erasmus Programme, the Amgen Scholars Programme, the Darwin Trust, the Thai Government, the Liechtenstein Government, the Turkish Government, the Cambridge Cancer Centre, Gates Cambridge Scholarships, GSK, Boehringer Ingelheim, APART, Funai Foundation, Worldwide Cancer Research, Dr Hadwen Trust, Swedish Society for Medical Research, Taiwan Government, EPSRC, the Innovative Medicines Initiative, Canadian Institutes of Health Research, Ataxia Telangiectasia Society, Rubicon, Birax, Leukaemia and Lymphoma Research, Thouron Award. The Gurdon Institute Postdoc Association (GIPA) was established in 2008. The aim of GIPA is to encourage scientific and social interactions, improve postdocs’ welfare and provide researcher development opportunities. GIPA organises a diverse set of events – annual Postdoc Retreats, Seminar Series featuring world-leading scientists, Career Paths discussion panels, Mentoring Scheme for junior postdocs and PhD students, and Happy Hours for the whole Gurdon Institute. In 2014 GIPA organised the 1st Gurdon Institute Postdoc Symposium, attended by 150 participants across the University, and featuring 4 invited keynote talks, 10 short talks from early career researchers and a poster session. RETREAT The 2014 Annual Retreat took place at the Five Lakes Hotel in Malden on 1st and 2nd October. Our special guest was Sir Patrick Maxwell. The Retreat is invaluable for both the exchange of scientific ideas and the social opportunities that it provides. Sources of funding 2014 ENERGY & ENVIRONMENT In July we held a tea party to celebrate our first milestone achievement of saving one million kWh of electricity since our energy saving campaign launched in March 2012. Institute members continue to reduce energy consumption, without affecting science, and they are key to the success of our long-term aim to embed energy awareness within the Institute culture. Our total savings to date are nearing 1.5 million kWh. This equates Professor Daniel St Johnston THE GURDON INSTITUTE 5 Julie Ahringer The regulation of chromatin structure and function Co-workers: Alex Appert, Fanelie Bauer, Ron Chen, Yan Dong, Csenge Gal, Carolina Gemma, Jürgen Jänes, Alicia McMurchy, Wei Qiang Seow, Przemyslaw Stempor, Annette Steward, Christine Turner, Carson Woodbury, Brian Wysolmerski Chromatin regulation plays a central role in the determination and expression of cellular identity, and chromatin disregulation is implicated in many diseases. We use C. elegans to investigate the developmental regulation of chromatin in transcription and genome organization. Towards understanding the role and regulation of chromatin during development, we have been mapping the locations of accessible DNA, transcription initiation, histone modifications, and chromatin regulators during development in wild-type and chromatin mutants. We found that that high promoter CpG density is a conserved genomic signal for open chromatin. We are studying the mechanism of CpG recognition and the function of marking of these regions by H3K4me3. Mapping transcription initiation revealed widespread bidirectional initiation at C. elegans enhancers and promoters. We are investigating the functions and developmental regulation of enhancers and non-coding transcription, and their relationship with promoters. Within chromatin, particular sets of histone modifications and/or chromatin proteins co-occur, and different “chromatin states” are associated with different genomic features. By generating and analysing a C. elegans chromatin state map, we found that the genome is organized into blocks of active and inactive chromatin separated by boundary regions. We are investigating the formation and function of different types of chromatin and how this global genomic organization arises. We also study the functions of C. elegans counterparts of major chromatin regulatory complexes implicated in human disease. In recent work, we found that transcriptional repression by the Retinoblastoma/ DRM complex involves facilitating a high level of the histone variant H2A.Z on the gene bodies of its targets. These results suggest a new avenue for the study of Retinoblastoma-related proteins. 6 THE GURDON INSTITUTE Selected publications: • Ho JW, 68 modENCODE consortium authors, Strome S, Elgin SC, Liu XS, Lieb JD, Ahringer J, Karpen GH and Park PJ (2014) Comparative analysis of metazoan chromatin architecture. Nature, 512, 449-452 Fig 2. C. elegans CFP-1/CXXC1 is targeted to CpG-rich promoters marked by H3K4me3 Fig 1. Genome-wide mapping of chromatin proteins and histone modifications • Weick E-M, Sarkies P, Silva N, Chen A-J, Moss SMM, Cording AC, Ahringer J, Martinez-Perez E and Miska EA (2014) PRDE-1 is a nuclear factor essential for the biogenesis of Ruby motif- dependent piRNAs in C. elegans Genes Dev, 28, 783-96 Fig 3. Chromatin states show that genes are organized into active and inactive blocks • Chen A-J, Stempor P, Down TA, Zeiser E, Feuer S and Ahringer J (2014) Extreme HOT regions are CpG dense promoters in C. elegans and human. Genome Research, 24: 1138-1146 • Chen A-J, Down TA, Stempor P, Chen QB, Egelhofer TA, Hillier LW, Jeffers TE and Ahringer J (2013) The landscape of RNA polymerase II transcription initiation in C. elegans reveals enhancer and promoter architectures. Genome Research, 8, 1339-47 Fig 4. Models for enhancer functions THE GURDON INSTITUTE 7 Andrea Brand Stem cells to synapses: regulation of self-renewal and differentiation in the nervous system Three-dimensional reconstruction of the blood-brain barrier glia (membranes in red) showing of the glia overlying neural stem cells (grey). Quiescent neural stem cells in the Drosophila central nervous system (membranes in green; nuclei in blue). Lola mutant neurons in the larval optic (labelled in green) dedifferentiate to a neural stem cell fate and express Deadpan (labelled in red; arrowheads). Without lola (green) to maintain repression, neurons dedifferentiate, proliferate and form tumours. Co-workers: Janina Ander, Josephine Bageritz, Elizabeth Caygill, Seth Cheetham, Melanie Cranston, Abhijit Das, Catherine Davidson, Paul Fox, Anna Hakes, Jun Liu, Owen Marshall, Leo Otsuki, Chloe Shard, Pauline Spéder, Christine Turner, Jelle Van Den Ameele, Mo Zhao Discovering how stem cells are maintained in a multipotent state and how their progeny differentiate into distinct cellular fates is a key step in the therapeutic use of stem cells to repair tissues after damage or disease. We are investigating the genetic networks that regulate neural stem cell behaviour. Neural stem cells in the adult brain exist primarily in a quiescent state but can be reactivated in response to changing physiological conditions. How do stem cells sense and respond to metabolic changes? In the Drosophila central nervous system, quiescent neural stem cells are reactivated synchronously in response to a nutritional stimulus. We showed that feeding triggers insulin production by blood-brain barrier glial cells, activating the insulin/IGF pathway in underlying neural stem cells and stimulating their growth and proliferation. More recently, we discovered that gap junctions in the blood-brain barrier glia mediate the influence of metabolic changes on stem cell behaviour, enabling glia to respond to nutritional signals and reactivate quiescent stem cells. The ability to reprogram differentiated cells into a pluripotent state has revealed that the differentiated state is plastic and reversible. Mechanisms must be in place to prevent neurons from dedifferentiating to a multipotent, stem cell-like state. We discovered that the BTB-Zn finger transcription factor, Lola, is required to maintain neurons in a differentiated state. In lola mutants, neurons dedifferentiate, turn on neural stem cell genes and begin to divide, forming tumours. Thus, neurons rather than stem cells or intermediate progenitors are the tumour-initiating cells in lola mutants. Cell-type specific transcriptional profiling is key to understanding cell fate specification and function. We developed ‘Targeted DamID’ (TaDa) to enable cell-specific profiling without cell isolation. TaDa permits genome-wide profiling of DNA- or chromatin-binding proteins without cell sorting, fixation or affinity purification. 8 THE GURDON INSTITUTE For more information, see the Brand lab home page: http://www.gurdon.cam.ac.uk/research/brand Selected publications: • Spéder P and Brand AH (2014) Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells. Developmental Cell 30, 309-321 • Southall TD, Davidson CM, Miller C, Carr A and Brand AH (2014) Dedifferentiation of neurons precedes tumour formation in lola mutants. Developmental Cell 28, 685-96 • Southall TD, Gold KS, Egger B, Davidson CM, Caygill EE, Marshall OJ and Brand AH (2013) Cell type-specific profiling of gene expression and chromatin binding without cell isolation: Assaying RNA Pol II occupancy in neural stem cells. Developmental Cell 26, 101-112 • Cheetham SW and Brand AH (2013) Insulin finds its niche. Science 340, 817-818 • Chell JM and Brand AH (2010) Nutrition-responsive glia control exit of neural stem cells from quiescence. Cell 143(7), 1161-1173 THE GURDON INSTITUTE 9 Nick Brown Molecular analysis of morphogenesis Co-workers: Natalia Bulgakova, Juan Manuel Gomez, Hannah Green, Benjamin Klapholz, Tarun Kumar, Miranda Landgraf, Aidan Maartens, John Overton, Peerapat Thongneuk Cellular adhesion and communication are vital during the development of multicellular organisms. These processes use proteins on the surface of cells, receptors, which stick cells together (adhesion) and/or transmit signals from outside the cell to the interior so that the cell can respond to its environment. Our research is currently focused on how adhesion receptors are linked with the cytoskeleton to specify cell shape and movement within the developing animal. This linkage between the adhesion receptors and the major cytoskeletal filaments contains many components, giving it the ability to grow or shrink in response to numerous signals. For example, as the cytoskeleton becomes contractile and exerts stronger force on the adhesion sites, additional linker proteins are recruited in to strengthen adhesion. We use the fruit fly Drosophila as our model organism to discover how the complex machinery linking cell adhesion to the cytoskeleton works, and contributes to morphogenesis. We are seeking to discover how adhesion receptors form contacts of differing strength and longevity, at one point mediating dynamic attachments as the cell moves, and at another point stable connections essential for the functional architecture of the body. A good example of stable sites of adhesion is the integrindependent attachments of the muscles (Fig 1). Normally integrin binding to extracellular ligands is the first step in assembling a large complex of intracellular integrinassociated proteins into an adhesion complex. Of particular interest are the mechanosensitive properties of cell adhesion, where acto-myosin contraction with the cell exerts force on sites of adhesion, causing the recruitment of proteins like vinculin to strengthen adhesion. By mimicking the action of force to generate an “activated” vinculin, we find that this protein can trigger adhesion complexes in the absence of integrins (Fig 2). We have been puzzled by the apparent lack of contribution of some integrin-associated proteins, as flies lacking these proteins seemed normal. However, by examining the muscles under the highest stress, the adult flight muscles, we are 10 THE GURDON INSTITUTE discovering new phenotypes (Fig. 3). Using advanced imaging methods including fluorescence lifetime imaging and super-resolution (Fig. 4) is revealing how the adhesion complex is assembled and functions. Selected publications: • Klapholz B, Herbert SL, Wellmann J, Johnson R, Parsons M and Brown NH (2015) Alternative mechanisms for talin to mediate integrin function. Curr Biol [in press] • Maartens A and Brown NH (2015) The many faces of cell adhesion during Drosophila muscle development. Dev Biol [in press] Fig 1. Attachment of muscles in the Drosophila embryo is mediated by integrins, which are linked to the actin cytoskeleton (red) by linker proteins such as vinculin (cyan). • Huelsmann S, Ylänne J and Brown NH (2013) Filopodialike actin cables position nuclei in association with perinuclear actin in Drosophila nurse cells. Dev Cell 26, 604-615. Fig 3. New phenotypes of integrin-associated proteins are being revealed by examining the highly-ordered flight muscles of the adult Drosophila (top normal [wild type], bottom mutant). Actin is in magenta and tropomyosin in yellow. • Bulgakova NA, Grigoriev I, Yap AS, Akhmanova A and Brown NH (2013) Dynamic microtubules produce an asymmetric E-cadherin-Bazooka complex to maintain segment boundaries. J Cell Biol 201, 887-901. • Bulgakova NA, Klapholz B and Brown NH (2012) Cell adhesion in Drosophila: versatility of cadherin and integrin complexes during development. Curr Opin Cell Biol 24, 702-712. Fig 4. Super-resolution view of the association between integrins (cyan) and actin (purple) at the contacts between the two epithelial cell layers that make up the wing. Fig 2. In the absence of integrins the muscles detach and round up (actin is in red), but activated vinculin is able to bypass the normal requirement for integrins to trigger the assembly of integrin-associated proteins into complexes (cyan). THE GURDON INSTITUTE 11 Jenny Gallop Membranes, actin and morphogenesis Co-workers: Guilherme Correia, Helen Fox, Lynn Froggett, Yoshiko Inoue, Iris Jarsch, Julia Mason, Daniel Saxton, Hanae Shimo We are interested in the molecular basis of cell shape and the changes that occur when cells move and tissues develop. Cell shape is in large part determined by the actin cytoskeleton and remodelling of the cytoskeleton underlies the cell rearrangements that occur during normal morphogenesis and also when morphogenetic programs go wrong, for example in developmental defects and during cancer metastasis. The machinery of the actin cytoskeleton is also hijacked by various pathogens to mediate infection. Actin filaments are nucleated at cell membranes and are elongated and bundled in different ways to form distinct cytoskeletal structures. We have found that the membrane environment influences which proteins are used to make actin structures. Membranes are interesting to consider in how cells change shape because they are the interface between the outside and inside of the cell and therefore are hubs of signalling activity, as well as being the boundary of the cell that has to be moulded by links to the cytoskeleton. We are particularly concentrating on how actin is polymerised during filopodia formation and endocytosis (Fig 1). We take a two-pronged approach: (1) reconstitution of actin polymerisation in vitro using artificial membranes and Xenopus egg extracts (Fig 2) and (2) investigation of how actin regulators are used by cells in vivo in Drosophila melanogaster and during early development in Xenopus laevis (Fig 3). This interdisciplinary approach gives us the possibility of attaining a complete molecular understanding and also testing those models within the natural complement of physiological signals provided by the whole organism. Selected publications: • Gallop JL, Walrant A, Cantley LC and Kirschner MW (2013) Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9. Proc Natl Acad Sci 110: 7193-7198 Fig 1. Filopodia protrude from cells and are made of bundled actin, vesicles bud inwards into cells and nucleate branched actin. • Lee K*, Gallop JL*, Rambani K and Kirschner MW (2010) Self-assembly of filopodia-like structures on supported lipid bilayers. Science 329: 1341-1345 • Gallop JL*, Jao CC*, Kent HM, Butler PJ, Evans PR, Langen R and McMahon HT (2006) Mechanism of endophilin N-BAR domain-mediated membrane curvature. EMBO J 25: 2898-2910 • Gallop JL, Butler PJ and McMahon HT (2005) Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission. Nature 438: 675-678 • McMahon HT and Gallop JL (2005) Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438: 590-596 (* joint first authors) Fig 2. Filopodia-like structures formed in vitro, with fluorescentlylabelled actin which grow from supported lipid bilayers. Fig 3. Total internal reflection fluorescence microscopy image of a Keller explant from a Xenopus gastrula, showing that actin regulator Toca-1 localises to lamellipodial edges, filopodia tips and endocytic vesicles. 12 THE GURDON INSTITUTE THE GURDON INSTITUTE 13 John Gurdon Nuclear reprogramming by oocytes and eggs Co-workers: Dilly Bradford, Nigel Garrett, Eva Hormanseder, Jerome Jullien, Magdalena Koziol, Kei Miyamoto, Mami Oikawa, Angela Simeone, Munender Vodnala, Ming-Hsuan Wen The overall aim of our research programme is to understand the mechanisms of somatic cell reprogramming. When a somatic cell nucleus is transplanted to an egg, it is within a few hours induced to change its pattern of gene expression from that of a somatic cell to that of an embryo. The same changes occur when the highly condensed and specialised sperm nucleus enters the egg at fertilisation and participation in normal development. The difference is that nearly 100% of sperm nuclei are reprogrammed perfectly whereas the great majority of nuclei from specialised somatic cells make this change imperfectly; they resist the reprogramming effects of egg cytoplasm. To analyse the mechanisms of reprogramming we transplanted multiple somatic nuclei to the germinal vesicles (nucleus) of an oocyte (the first meiotic prophase progenitor of an egg). Nuclei transplanted to oocytes do not divide or synthesise DNA, as they do when transplanted to an egg, but nevertheless nearly all of them are induced to undergo the first stages of new gene expression. During this year we have achieved a first full description of major events that lead to reprogramming by oocytes. A rapid sequence of steps is seen, at the single nucleus and defined time course level, to lead in a hierarchical manner to the binding and phosphorylation of RNA polymerase II. The whole process is independent of new protein synthesis. We have also described the phenomenon of a “mitotic advantage”, in which some genes in mitotic nuclei are up to 100 times more efficiently reprogrammed by oocytes than in similar somatic nuclei in interphase. We propose that in normal development, mitosis is a stage in the cell cycle when transcription factors in chromatin are extensively exchanged leading to new directions of cell differentiation. 14 THE GURDON INSTITUTE Fig 1. New RNAs from transplanted reprogrammed nuclei. Fig 2. Single nucleus analysis of nuclear reprogramming by oocytes. Selected publications: • Gurdon JB (2013) Secrets in the egg. Cell 153: 1179. • Jullien J, Miyamoto K, Pasque V, Allen GE, Bradshaw CR, Garrett NJ, Halley-Stott RP, Kimura H, Ohsumi K and Gurdon JB (2014) Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming. Molecular Cell 55, 1-13. • Halley-Stott RP, Jullien J, Pasque V and Gurdon JB (2014) Mitosis gives a brief window of opportunity for a change in gene transcription. PLoS Biology 12(7) e1001914. (a) (a)  (b) • Christophorou MA, Castelo-Branco G, Halley-Stott RP, Oliveira CS, Loos R, Radzisheuskaya A, Mowen KA, Bertone P, Silva JCR, Zernicka-Goetz M, Nielsen ML, Gurdon JB and Kouzarides T (2014) Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature doi: 10.1038/nature12942. (a) • Teperek M, Miyamoto K, Simeone A, Feret, Deery, Gurdon JB and Jullien J (2014) Sperm and spermatids contain different proteins and bind distinct egg factors. International Journal of Molecular Science 15(9):16719-16740. Fig 4. Mitotic advantage is maintained after nuclear sonication. Fig 3. (a) Design of mitotic advantage experiment. (b) Mitotic chromatin is strongly reprogrammed to Sox2 transcription. Fig 5. Procedure to achieve different levels of cell permeabilization before nuclear transfer. THE GURDON INSTITUTE 15 Meritxell Huch Fig 1a Fig 1b Stem cells and tissue regeneration - implications in disease and cancer Co-workers: Luigi Aloia, Laura Broutier, John Crang, Chris Hindley, Bart Kramer, Gianmarco Mastrogiovanni, Alessandra Merenda, Mikel Mckie In adult mammals, self-renewal is required for the maintenance of tissue homeostasis and tissue repair. In organs with extensive self-renewal, such as the intestine and stomach, adult stem cell populations are constantly cycling to maintain cellular turnover. In organs with limited proliferative capacity, though, such as the liver or pancreas, we have recently described a population of stem/ progenitor cells that become activated exclusively upon damage to repair the lost tissue and reinstall homeostasis. However, the mechanism that regulates the activation of the cells during regeneration, from the implication of the niche to the epigenetic mechanisms regulating this activation remains unsolved. One of our main goals is to understand the mechanism of adult tissue regeneration, using the liver and pancreas as model organs. Chronic liver disease and liver and pancreas cancer are highly associated to inflammation and tissue damage. Understanding the mechanism regulating these processes holds promise to extend our knowledge on tissue regeneration, disease and cancer. We are also interested in tissue engineering and disease modelling. Despite the enormous regenerative capacity of the liver in vivo, liver cells have resisted expansion in culture. We have recently described a culture system (liver organoid culture) that allows, for the first time, the long-term (>1year) expansion of mouse liver stem/ progenitor cells into 3D structures that we have termed ‘liver organoids’. In this novel culture system adult liver stem/progenitor cells maintain their ability of selfrenewal and differentiation towards functional liver cells. When transplanted into a mouse model of liver disease (FAH-/- mice), the cultured cells partially rescued the liver phenotype, showing their therapeutic potential. We have observed similar results using adult pancreas tissue. Following on that discovery, we would now like to transfer this technology to the study of liver diseases with the aim of better understanding these and potentially finding better therapeutic strategies. 16 THE GURDON INSTITUTE Selected publications: Fig 1c • Huch M*, Bonfanti P*, Boj SF*, Sato T*, Loomans CJ, van de Wetering M, Sojoodi M, Li VS, Schuijers J, Gracanin A, Ringnalda F, Begthel H, Hamer K, Mulder J, van Es JH, de Koning E, Vries RG, Heimberg H and Clevers H (2013) Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J 32(20):2708-21 • Huch M*, Dorrell C*, Boj SF, van Es JH, Li VSW, van de Wetering M, Sato T, Hamer K, Sasaki N, Finegold MJ, Haft A, Vries R, Grompe M and Clevers H (2013) In vitro expansion of single Lgr5+ liver stem cells induced by Wntdriven regeneration. Nature 494: 247-50 • Barker N*, Huch M*, Kujala P, van de Wetering M, Snippert HJ, van Es JH, Sato T, Stange DE, Begthel H, van den Born M, Danenberg E, van den Brink S, Korving J, Abo A, Peters PJ, Wright N, Poulsom R and Clevers H (2010) Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6(1):25-36 (* denotes joint first authors) Fig .1a–c, Lgr5-lacZ mice were injected i.p. with corn oil or CCl as in Fig. 1. Six days later, liver tissue was dissociated to single cells, loaded with the fluorescent b-galactosidase (CMFDG) substrate and analysed by fluorescent-activated cell sorting (FACS). Sorted isolated Lgr5-LacZ+ cells were cultured at a ratio of onesingle Lgr5-LacZ+ cell per well (clonal) as described in the Methods. a, Scheme representing the protocol used. b, Representative FACS plot of dissociatedsingle cells from CCl-treated (with CCl) and non-treated (without CCl) livers. Cells were gated following sequential selection by cell-size (forward scatter(FSC) versus side scatter (SSC)) and propidium iodide (PI) exclusion. Viable CMFDG+PI− cells were selected and sorted. Representative sorted cell is shown. c, Serial differential interference contrast (DIC) images showing the outgrowth of a single Lgr5-LacZ+ cell. Original magnifications were ×40 (days 0–5), ×20(day 7–11), ×10 (day 19) and ×4 (1 month onwards). P, passage. Fig 2. Human liver organoid derived from a human liver biopsy of a healthy donor and grown for >4 months in culture THE GURDON INSTITUTE 17 Steve Jackson Maintenance of genome stability Co-workers: Pallavi Agarwal, Gabriel Balmus, Linda Baskcomb, Rimma Belotserkovskaya, Andrew Blackford, Will Chiang, Julia Coates, Matt Cornwell, Mukerrem Demir, Kate Dry, Josep Forment, Yaron Galanty, Nicola Geisler, Mareike Herzog, Satpal Jhujh, Delphine Larrieu, Carlos le Sage, Natalia Lukashchuk, Francisco Muñoz-Martinez, Ryotaro Nishi, Fabio Puddu, Helen Reed, Israel Salguero, Christine Schmidt, Matylda Sczaniecka-Clift, Rohan Sivapalan, David Weismann, Paul Wijnhoven Our work focuses on the DNA-damage response (DDR), the set of events that optimises cell survival and genome integrity by detecting DNA damage, signalling its presence and mediating its repair. As DDR defects are associated with neurodegenerative diseases, immunodeficiencies, premature ageing and cancer, our research is not only providing academic insights but is also suggesting new ways better to understand and alleviate such conditions. This work extended the list of DUBs linked to the DDR and highlighted their potential as cancer therapy targets. One highlight for our research during the past year was us identifying the small molecule “Remodelin” that improves nuclear architecture, chromatin organisation and fitness of human lamin A/C-depleted cells and cells from patients with the premature-ageing disease Hutchinson-Gilford progeria syndrome. These findings provided insights into how the Remodelin target protein, NAT10, affects nuclear architecture and suggested strategies for treating laminopathies and cancer. • Nishi R, Wijnhoven P, le Sage C, Tjeertes J, Galanty Y, Forment JV, Clague MJ, Urbé S and Jackson SP (2014) Systematic characterization of deubiquitylating enzymes for roles in maintaining genome integrity. Nature Cell Biology 16, 1016-1026 In addition, we have shown that rolled-up transparent microtubes can serve as cell culture scaffolds that precisely define the space available for single cell growth. This work established that the spatial confinement of mitotic mammalian cells inside tubular architectures can perturb metaphase plate formation, delay mitotic progression, and cause chromosomal instability in both transformed and nontransformed human cell lines. These findings could provide important clues into how spatial constraints dictate cellular behaviour and function. Another particularly notable achievement for us in 2014 was our work systematically screening deubiquitylating enzymes (DUBs) for roles in maintaining genome integrity. We identified a number of DUBs with previously unknown links to double-strand break (DSB) repair, the G2/M DNA damage checkpoint and genome integrity maintenance. Furthermore, we established that the DUB UCHL5 regulates DSB resection and homologous recombination through protecting its interactor, NFRκB, from degradation. 18 THE GURDON INSTITUTE Protein dynamics to and from sites of DNA breaks. DNA damage checkpoint and repair factors and modulators of chromatin organization are recruited (green arrows) to DNA breaks (SSB and DSB), while transcription machineries are excluded (red arrows), and the dynamics of structural chromatin components operate in both directions (orange arrows). HR, homologous recombination; NHEJ, non-homologous end joining. Taken from Polo SE and Jackson SP (2011) Dynamics of DNA damage response at DNA breaks: A focus on protein modifications. Genes Dev 25, 409-433 Selected publications: • Larrieu D, Britton S, Demir M, Rodriguez R and Jackson SP. (2014) Chemical inhibition of NAT10 corrects defects of laminopathic cells. Science 344, 527-532 • Blasius M, Wagner SA, Choudhary C, Bartek J and Jackson SP (2014) A quantitative 14-3-3 interaction screen connects the nuclear exosome targeting complex to the DNA damage response. Genes and Development 28, 1977-1982 Rolled up functionalised nanomembranes as three-dimensional cavities for single cell studies • Xi W, Schmidt CK*, Sanchez S*, Gracias DH, CarazoSalas RE, Jackson SP and Schmidt OG (2014) Rolled-up functionalized nanomembranes as three-dimensional cavities for single cell studies. NANOLetters 14(8) 41974204 *Co-corresponding authors Image shows a laminopathic cell with a mis-shapen nucleus before (left) and after (right) chemical inhibiton of the N-acetyl transferase NAT10. THE GURDON INSTITUTE 19 Tony Kouzarides Epigenetic modifications and cancer Co-workers: Andrej Alendar, Paulo Amaral, Andy Bannister, Isaia Barbieri, Ester Cannizzaro, Ka Hing (Harvey) Che, Ali Cook, Namshik Han, Sri Lestari, Nikki Mann, Valentina Migliori, Gonzalo Millan Zambrano, Sam Robson, Helena Santos Rosa, Meike Wiese Our group is interested in defining the mechanisms by which modifications of chromatin and non-coding (nc) RNAs regulate cellular processes. Our attention is focused on enzymes which regulate transcription by covalently modifying histones or ncRNAs. We would like to understand what biological processes these enzymes control and the precise mechanism by which modifications act. At the same time we are dissecting how modification pathways are mis-regulated in cancer cells and exploring avenues for treatment. Our recent work has identified two new modification pathways. The first involves methylation of miRNA 145 by a new RNA modifying enzyme BCDN3D. This methylation disrupts the binding of miRNA 145 to dicer and therefore controls miRNA maturation. The BCDN3D enzyme is an oncogene with pro-metastatic characteristics, indicating that this pathway may be therapeutically important. The second pathway involves a new class of chromatin modifying enzyme, which is able to methylate a glutamine residue within H2A. This modification is restricted to the rDNA locus and has a role in transcription by RNA polymerase I. We have also continued the characterisation of arginine cirtrullination by the Padi4 enzyme, a modification we described some years ago. We can now show that this enzymatic activity has a role in pluripotency. Our interest in the intervention of epigenetic pathways involved in cancer has identified the acetyl-binding BET proteins as a therapeutic target. A small molecule inhibitor of BETs (I-BET) was used to prevent the binding of BET proteins to acetylated histones and suppress a gene expression program leading to MLL-leukaemia. This small molecule effectively inhibits primary human leukaemias and halts the process of leukaemia in model systems. I-BET is currently in clinical trials. 20 THE GURDON INSTITUTE Fig 1. Citrullination by PADI4 regulates pluripotency by causing chromatin de-compaction Selected publications: • Christophorou M, Castelo-Branco G, Halley-Stott R, Slade Oliveira C, Loos R, Bertone P, Silva J, Zernicka-Goetz M, Nielsen M, Gurdon JB, Radzisheuskaya A, Mowen M and Kouzarides T (2014) Citrullination regulates pluripotency and H1 linker histone binding to chromatin. Nature 507(7490), 104-108 • Tessarz P, Santos-Rosa H, Robson SC, Sylvestersen KB, Nelson CJ, Nielsen ML and Kouzarides T (2014) Glutamine methylation in Histone H2A is an RNA Polymerase I dedicated modification. Nature 505(7484), 564-568 • Xhemalce B, Robson S and Kouzarides T (2012) Human RNA Methyltransferase BCDIN3D Regulates MicroRNA Processing. Cell 151(2), 278-288 • Dawson M, Kouzarides T et al (2011) Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478(7370), 529-533 Fig 2. Glutamine methylation of H2A by the human Fibrillarin enzyme is localised in the nucleus and regulates rDNA transcription. • Bartke T, Vermeulen M, Xhemalce B, Robson SC, Mann M and Kouzarides T (2010). Nucleosome-interacting Proteins Regulated by DNA and Histone Methylation. Cell 143: 470 – 84 Fig 3. The small molecule I-BET displaces BET proteins and represses genes that cause MLL-leukaemia. THE GURDON INSTITUTE 21 Rick Livesey Mammalian neural stem cell biology, fundamental and applied Co-workers: Philipp Berg, Laura Brightman, Philip Brownjohn, Tatyana Dias, lewis Evans, Jayne Fisher, Alberto Frangini, Teresa Krieger, Ayiba Momoh, Steven Moore, Tomoki Otani, Nathalie Saurat, James Smith, Victoria Stubbs The cerebral cortex, which makes up three quarters of the human brain, is the part of the nervous system that integrates sensations, executes decisions and is responsible for cognition and perception. Given its functional importance, it is not surprising that diseases of the cerebral cortex are major causes of morbidity and mortality. Understanding the biology of cortical neural stem cells is essential for understanding human evolution, the pathogenesis of human neurodevelopmental disorders and the rational design of neural repair strategies in adults. During embryonic development, all of the neurons in the cortex are generated from a complex population of multipotent stem and progenitor cells. Much of the research in the lab centres on the cell and molecular biology of cortical stem cells. We are particularly interested in the molecular mechanisms controlling multipotency, self-renewal and neurogenesis, and how these are coordinated to generate complex lineages in a fixed temporal order. A number of ongoing projects in the group address the functional importance of transcriptional and epigenetic mechanisms in this system. In the other major strand of research in the group, we have developed methods for directing differentiation of human pluripotent stem cells to cortical neurons, via a cortical stem cell stage. Human stem-cell-derived cortical neurons form functional networks of excitatory synapses in culture. We are using this system for studies of human neural stem cell biology and to generate models of cortical diseases. Our initial focus has been on dementia, where we have used stem cells from people with Down syndrome and from patients with familial Alzheimer’s disease to create cell culture models of Alzheimer’s disease pathogenesis in cortical neurons. We are using those models to study Alzheimer’s disease pathogenesis and the efficacy of current therapeutic strategies. 22 THE GURDON INSTITUTE Selected publications: • Livesey FJ (2014) Human stem cell models of dementia. Human Molecular Genetics doi:10.1093/hmg/ddu302 • Olsson B, Legros L, Guilhot F, Strömberg K, Livesey FJ, Wilson DH, Zetterberg H and Blennow K (2014) Imatinib treatment and Aß42 in humans. Alzheimer’s and Dementia epub ahead of print. • Alsiö JM, Tarchini B, Cayouette M, and Livesey FJ (2013) Ikaros promotes early-born neuronal fates in the cerebral cortex. PNAS 110: E716–E725. • Shi Y, Kirwan P, Smith J, Robinson HP and Livesey FJ (2012) Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. Nat Neurosci 15, 477-486 Fig 1. Human stem cell-derived neuroepithelial rosettes in cell culture Fig 2. Human stem cellderived excitatory neurons. Fig 3. Axons of human stem cellderived neurons in a microfluidic device. Figure 4. Superresolution image of GFP (green) and mCherry (red) labelled microtubule-binding proteins on microtubules (blue) in human axons and dendrites. THE GURDON INSTITUTE 23 Eric Miska Fig 1. We have discovered that let-7, LIN-28 and the poly(U) polymerase form an ultraconserved switch that regulates stem cell decisions in C elegans Non-coding RNA and genome dynamics Co-workers: Alper Akay, Alyson Ashe, Fabian Braukmann, Tomas di Domenico, Tanay Ghosh, Sabrina Huber, Joanna Kosalka, Miranda Landgraf, Jéremie le Pen, Milan Malinsky, Eyal Maori, Ragini Medhi, Marc Ridyard, Alexandra Sapetschnig, Mélanie Tanguy, Eva-Maria Weick RNA is at the heart of cellular and organismal control with non-coding RNA emerging as a major regulator of many biological processes. We are interested in all aspects of regulation by non-coding RNA. Our goal is to understand how non-coding RNAs regulate development, physiology and disease, in particular human cancer. Current research themes include: miRNA biology and pathology, miRNA mechanism, piRNA biology and the germline, endo-siRNAs in epigenetic inheritance and environmental conditioning, small RNA evolution, RNA modification and the role of RNAi in host pathogen interaction. For example: piRNAs are animal-specific small RNAs usually restricted to the germline and required for fertility. In 2008 we identified the piRNAs of C. elegans. We have demonstrated that Piwi proteins and piRNAs are important for gemline development and fertility. In the absence of piRNAs germline genome integrity is compromised and consequently piRNAs have been called “guardians of the genome”. Now we are investigating how piRNAs are generated in the germline and how they act to silence their targets. We are also working to understand how the piRNA pathway responds to foreign DNA/RNA and how this pathway is evolving. We are using a combination of molecular genetics, biochemical and computational approaches to study RNA. Model organisms have been key in unravelling almost all biological processes. With a 100 Mb genome, three days generation time and an established genetic toolkit, C elegans is the ideal starting point to address many questions in RNA biology. In addition, we are taking advantage of mammalian models and human cell culture. 24 THE GURDON INSTITUTE Selected publications: • Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska EA and Mansuy IM (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci 17(5): 667-9 • Ashe A, Bélicard T, Le Pen J, Sarkies P, Frézal L, Lehrbach NJ, Félix MA, Miska EA (2013) A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity. E-Life 2:e00994 • Sarkies P and Miska EA (2012) Molecular biology. Is there social RNA? Science 341(6145), 467 - 468 • Ashe A, Sapetschnig A, Weick EM, Mitchell J, Bagijn MP, Cording AC, Doebley AL, Goldstein LD, Lehrbach NJ, Le Pen J, Pintacuda G, Sakaguchi A, Sarkies P, Ahmed S and Miska EA (2012) piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 150, 88-99 • Bagijn MP, Goldstein LD, Sapetschnig A, Weick EM, Bouasker S, Lehrbach NJ, Simard MJ and Miska EA (2012) Function, targets, and evolution of Caenorhabditis elegans piRNAs. Science 337, 574 - 578 Fig 2. An in-vivo assay for piRNA function in the germline. piRNAs and Piwi proteins protect the germline. We are using molecular genetics, cell biology and high-throughput sequencing to discover miRNA biogenesis and mechanisms. Fig 3. RNA-mediated transgenerational epigenetic inheritance in C elegans THE GURDON INSTITUTE 25 Eugenia Piddini Fig 1. Stress signaling and cell competition. Loser Minute -/+ mutant cells chronically activate the JNK reporter Puc-LacZ and the JAK/STAT ligand Unpaired-3 in the adult fly gut (top and bottom, respectively, compare wt gut on the left to Minute -/+ gut on the right). Competitive cell interactions in normal physiology and cancer Co-workers: Michael Dinan, Maja Goschorska, Golnar Kolahgar, Kasia Kozyrska, Iwo Kucinski, Kathy Oswald, Saskia Suijkerbuijk, Silvia Vivarelli, Laura Wagstaff The elimination of suboptimal cells from tissues is an important process that helps preserve tissue function. Cell competition is a quality control mechanism that achieves exactly that: when suboptimal cells are present, they are recognised by surrounding fitter cells, which eliminate them through competition. Much of the work in our lab focuses on investigating the mechanisms and the physiological role of this phenomenon, combining work in Drosophila and in mammalian cell culture models. Through transcriptional profiling we have identified a molecular signature common to cells that are normally outcompeted in Drosophila wing imaginal discs. This has allowed us to identify a number of genes and signaling pathways that we have found to play a role in cell competition and which we are currently investigating further. Cell competition has been mostly studied in developing tissues, but recently has also been observed in adult tissues. This has important implications, as selection of fitter cells during adult tissue maintenance can lead to improved health and potentially delay tissue ageing. Our lab studies the mechanism and relevance of cell competition in adult tissues using the adult Drosophila gut as a model. Through these studies we found that the JNK and JAK/STAT signaling pathways, activated in loser cells, help promote the proliferation of fitter stem cells. In addition the lab investigates the role of cell competition in cancer. Indeed it has been suggested that precancerous cells could act as supercompetitors and kill surrounding normal cells. For these studies we use a fly model of adult intestinal adenoma and there we have shown that indeed growing adenoma cells kill surrounding normal tissue. We are currently investigating the relevance of this for tumour growth. 26 THE GURDON INSTITUTE Selected publications: • Graml V, Studera X, Lawson JL, Chessel A, Geymonat M, Bortfeld-Miller M, Walter T, Wagstaff L, Piddini E and Carazo-Salas RE (2014) A genomic multi-process survey of the machineries that control and link cell shape, microtubule organisation and cell cycle progression. Dev Cell 31(2):227-39 Journal Cover • Wagstaff L, Kolahgar G and Piddini E (2013) Competitive cell interactions in cancer: a cellular tug of war. Trends in Cell Biology 23(4):160-7. • Vincent JP*, Kolahgar G, Gagliardi M and Piddini E* (2011) Steep differences in Wingless signalling trigger Myc-independent competitive cell interactions. Dev Cell 366-374 * Corresponding authors Fig 2. Adenoma cells suppress the growth of neighbouring normal cells. We can generate fly guts in which normal and mutated adenoma cells (identified by differential GFP/RFP labeling) co-exist as shown in the top panels. This approach shows that wt cell clones (RFP negative, bottom panels) are much tinier if they grow alongside adenoma (right) cells than if they grow next to other wild-type cells (left). • Piddini E and Vincent JP (2009) Interpretation of the Wingless gradient requires signalling-induced self-inhibition (2009). Cell 136, 296-307 • Vivarelli S, Wagstaff L and Piddini E (2012) Cell wars: regulation of cell survival and proliferation by cell competition. Essays Biochem 10;53(1):69-82 Fig 3. Mechanical cell competition: we have discovered a new type of cell competition whereby cells are eliminated because of hypersensitivity to crowding. As shown here, while normal MDCK cells grow well and increase in density with time, ScribbleKD loser cells grown at the same density are inhibited in growth. THE GURDON INSTITUTE 27 Jonathon Pines How do cells control mitosis? Co-workers: Barbara Di Fiore, Anja Hagting, Andrew Harrison, Daisuke Izawa, Mark Jackman, Chiara Marcozzi, Oxana Nashchekina, Bernhard Strauss, Jill Temple, Samuel Wieser, Claudia Wurzenberger, Keiko Yata A dividing cell must ensure that the two daughter cells receive an equal and identical copy of the genome, and this is the focus of our research. We aim to determine how cells regulate entry to mitosis and subsequently coordinate chromosome segregation with cell separation.We know that mitosis is controlled by the interplay between protein kinases, protein phosphatases, and APC/C-mediated proteolysis, and to understand the rapid and complex dynamics of mitosis it is essential to study these processes in living cells, complemented by biochemical analyses. We introduce fluorescent tags into the genes encoding our proteins of interest by homologous recombination to enable us to measure protein numbers and kinetics in vivo, which we can use to inform molecular models. To understand how cells trigger mitosis we are analysing the behaviour of the key mitotic kinases and their regulators. We developed a FRET biosensor to assay the dominant mitotic kinase, Cyclin B1-Cdk1, in vivo and are using this to define the pathways that regulate the timing of mitosis. To identify the proteins responsible for regulating the Cyclin-Cdks, and provide insights into CyclinCdk substrates, we analyse protein complexes through the cell cycle by SILAC mass spectrometry. To understand how proteolysis regulates progress through mitosis we complement the analysis of APC/C-dependent degradation in living cells with biochemical analyses of protein complexes and ubiquitination activity. These studies are revealing how the APC/C is activated and how it is able to select a particular protein for destruction at a specific time. The crucial role of the Spindle Assembly Checkpoint in controlling the APC/C to regulate chromosome segregation has meant that our recent work has elucidated the mechanisms of some of the key steps in the checkpoint pathway, and revealed how the checkpoint is able to rapidly inactivate the APC/C. 28 THE GURDON INSTITUTE Mass spectroscopy analysis reveals the dynamic interactions of the different cyclins through the cell cycle. Credit: Felicia Walton-Pagliuca & Mark Collins (Sanger Institute) Selected publications: • Izawa D and Pines J (2015) The Mitotic Checkpoint Complex binds a second CDC20 to inhibit active APC/C. Nature 517, 631-634 • Collin P, Nashchekina O, Walker R and Pines J (2013) The spindle assembly checkpoint works like a rheostat not a toggle-switch Nat Cell Biol 15, 1378-1385 • Mansfeld J, Collin P, Collins MO, Choudhary J and Pines J (2011) APC15 drives the turnover of MCC-Cdc20 to make the spindle assembly checkpoint responsive to kinetochore attachment. Nat Cell Biol 13, 1234-1244. • Pagliuca F, Collins MO, Lichawska A, Zegerman P, Choudhary JS and Pines J (2011) Quantitative proteomics reveals the basis for the biochemical specificity of the cell cycle machinery. Mol Cell 43, 406-417. • Gavet O and Pines J (2010) Progressive activation of Cyclin B1-Cdk1 coordinates entry to mitosis. Dev Cell 18, 533-543. Mitotic RPE-1 cell with a single unattached chromosome. Mad2 in red, Hec1 in green, DNA in blue and spindle MTs in white. (Philippe Collin) Montage of a prometaphase cell in which the Venus fluorescent protein has been knocked into the Mad2 locus. Mad2 binds to unattached kinetochores.The chromosomes are labelled with ectopically expressed Histone H2B-mRuby. (Philippe Collin) THE GURDON INSTITUTE 29 Emma Rawlins Adult mouse lung section showing lineage-labelled secretory cells (green) in the conducting airways. Stem and progenitor cells in the mammalian lung Co-workers: Gayan Balasooriya, Christoph Budjan, Jo-Anne Johnson, Usua Laresgoiti Garay, MarKo Nikolic Our lungs have a complex three-dimensional structure which facilitates respiration and host defence. Building this structure requires that lung embryonic progenitor cells produce the correct types and numbers of cells in the correct sequence. How is this controlled? And how is the final structure maintained in the adult? Our lab investigates the cellular and molecular mechanisms which control stem and progenitor cell fate decisions in the developing and adult lungs. Key unanswered questions include what mechanisms control the decision of lung progenitors to self-renew or to differentiate? Which pathways are required for cell lineage specification in the lung? Our approach is to use the power of mouse genetics to understand the control of lung progenitor cell behaviour at the single cell level. This allows individual cells to be analysed quantitatively in vivo, or by live-imaging in organ culture systems. We have previously shown that in the embryonic lung there is a population of Id2+ multipotent epithelial progenitor cells located at the distal tips of the budding epithelium. The developmental potential, or competence, of these cells changes during embryogenesis. At the same time the cells undergo a change in gene expression pattern. We are currently exploring the cellular and molecular basis of this change in competence. The identity of the epithelial stem and progenitor cells in the postnatal lung remains controversial. Our previous work has shown that each anatomical region (trachea, bronchioles, alveoli) has its own progenitor cell population and that the behaviour of these progenitors can change in response to local conditions. Our current postnatal work focuses on: • Better characterising the adult lung progenitor cells. This includes testing whether progenitor cell behaviour is widespread or there are stem cells. • Understanding the genetic regulation of the progenitors under several different physiologically-relevant conditions. 30 THE GURDON INSTITUTE In particular, we are focusing on genes that are hypothesised to control the decision to self-renew or differentiate. Our long-term vision is to combine the developmental and homeostatic aspects of our work to develop new approaches to ameliorate human pulmonary disease. In particular, we are working towards being able specifically to direct endogenous lung stem cells to generate any lung epithelial cell type. Selected publications: • Rawlins EL, Okubo T, Xue Y, Brass DM, Auten RL, Hasegawa H, Wang F and Hogan BLM (2009) The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 4 525-534 • Rawlins EL, Clark CP, Xue Y and Hogan BLM (2009) The Id2 distal tip lung epithelium contains individual multipotent embryonic progenitor cells. Development 136 3741-3745 • Rawlins EL (2011) The building blocks of mammalian lung development. Developmental Dynamics 240 463-76 Mouse embryonic lung growing in culture. Blue (X-gal staining) shows grafted stem cells which have been incorporated into the lung structure. • Onaitis M, D’Amico TA, Clark C, Guinney J, Harpole DH and Rawlins EL ( 2011) A 10-gene progenitor cell signature predicts prognosis in lung adenocarcinoma. Annals of Thoracic Surgery 91 1046-50 Mouse embryonic lung undergoing branching morphogenesis, stained to show the epithelium (E-cadherin). A clone of mutant tracheal epithelial cells labelled with GFP (green). THE GURDON INSTITUTE 31 Ben Simons Mechanisms of stem cell fate in development, maintenance, and diseased states Co-workers: Juergen Fink (Stem Cell Institute), Philip Greulich (Cavendish), Edouard Hannezo (Cavendish), Teresa Krieger, Crystal McClain (Stem Cell Institute), Steffen Rulands (Cavendish) The coordination of cell proliferation and fate specification is central to the development and maintenance of tissues. In development, systems must be tightly-regulated to ensure that precise numbers of lineage-specified cells are generated in the correct sequence whilst, in adult, a delicate balance between proliferation and differentiation is essential for homeostasis. Through a programme of multidisciplinary and collaborative research, our group develops biophysical approaches to identify unifying principles of stem cell regulation in the development and maintenance of tissues, and to use the insights to resolve pathways leading to dysregulation in diseased states. Applying methods from statistical physics, we have shown that strategies of stem cell self-renewal can be grouped into one of four “universality” classes according to whether the balance between proliferation and differentiation is achieved at the level of individual cells or the population, and whether regulation follows from intrinsic (cell-autonomous) processes or is mediated by signals from the niche. By combining lineage tracing studies with marker-based assays, we have used these insights to show that different mammalian epithelial tissues, including epidermis, oesophagus, intestine, trachea, and germline conform to population asymmetry, in which stem cells are lost and replaced, leading to “neutral drift” dynamics and consolidation of clonal diversity. Lately, by combining static clonal labeling assays with intravital in vivo live-imaging approaches, we have found that both intestinal and germline stem cells are functionally heterogeneous, with cells moving reversibly between “primed” states, biased for self-renewal or differentiation and loss. This process of “dynamical heterogeneity” has established a new paradigm for tissue maintenance, with ramifications for stem cell identity and function. Building on the success of this programme, we have used parallel approaches to identify patterns of progenitor cell fate in the development of tissues, including the neocortex and heart, as well as in processes leading to dysregulation in diseased states. Peter Dirks, Bill Harris, Meritxell Huch, Rick Livesey, Eugenia Piddini, Emma Rawlins, Wolf Reik, Jacco van Rheenen, Songhai Shi, Hongjun Song, and Shosei Yoshida. Selected publications: • Gao P, Postiglione MP, Krieger TG, Hernandez L, Wang C, Han Z, Streicher C, Papusheva E, Insolera R, Chugh K, Kodish O, Huang K, Simons BD, Luo L, Hippenmeyer S and Shi SH (2014) Deterministic progenitor behavior and unitary production of neurons in the neocortex. Cell 159, 775-88 • Hara K, Nakagawa T, Enomoto H, Suzuki M, Yamamoto M, Simons BD and Yoshida S (2014) Mouse spermatogenic stem cells continually interconvert between equipotent singly isolated and syncytial states. Cell Stem Cell 14, 658-72 • Ritsma L, Ellenbroek SI, Zomer A, Snippert HJ, de Sauvage FJ, Simons BD, Clevers H and van Rheenen J (2014) Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature 507, 362-5 • Mascre G, Dekoninck S, Drogat B, Youssef KK, Brohee S, Sotiropoulou PA, Simons BD and Blanpain C (2012) Distinct contribution of stem and progenitor cells to epidermal maintenance. Nature 489, 257-62 • Driessens G, Beck B, Caauwe A, Simons BD and Blanpain C (2012) Defining the mode of tumour growth by clonal analysis. Nature 488, 527-30 Studies of clonal fate using a multicolour inducible genetic labelling system provide a vivid demonstration of neutral drift dynamics and the progession towards monoclonality in crypt. The top image shows a section through the base of the crypt showing the clonal progeny of the stem/paneth cell compartment at 7 days post-induction. The bottom image shows the migration streams of differentiated cells moving up (fully-clonal crypts) and onto villi. Inducible genetic labelling allows the fate of progenitor cells and their progeny to be traced in epidermis both in normal and diseased states. The figure shows the progeny of a GFP labelled cell in a squamous tumour in mouse. Such lineage tracing assays allows for the in vivo characterisation of the tumour-initiating potential of tumour cells, and the study of the progression from benign papilloma to invasive squamous carcinoma. Genetic lineage tracing of mouse heart development using a multicolour confetti reporter allows the potency of early Mesp1 expressing cells to be resolved, and provides insight into tissue morphogenesis. Current collaborators include Cedric Blanpain, Hans Clevers, 32 THE GURDON INSTITUTE THE GURDON INSTITUTE 33 Daniel St Johnston Polarising epithelial cells and body axes Co-workers: Dan Bergstralh, Catiá Carvalho, Jia Chen, Nicole Dawney, Hélène Doerflinger, Artur Fernandes, Weronika Fic, Jackie Hall, Holly Lovegrove, Nick Lowe , Dmitry Nashchekin, Avik Mukherjee, Jennifer Richen, George Sirinakis, Vanessa Stefanak, Vitor Trovisco, Helen ZennerBranco Cell polarity is essential for normal cell shape and function and underpins key developmental processes, such as cell migration, axis determination and asymmetric stem cell divisions, whereas a loss of polarity is a hallmark of tumours. We are using Drosophila and mammalian tissue culture cells to analyse how cells polarise and how cortical polarity factors regulate other polarised aspects of cell behaviour. Most organs in the body are composed of epithelial cells that polarise along their apical-basal axes and adhere to each other to form sheets of cells that act as barriers between compartments. We use the follicular epithelium that surrounds the developing Drosophila egg chamber as a model to investigate how apical-basal polarity is established in a secretory epithelium and how polarity factors control the organisation of the microtubule cytoskeleton. For example, we have analysed how the mitotic spindle is oriented to ensure that both daughter cells remain within epithelium, as mis-oriented spindles have been proposed to contribute to tumour development. We have also started to examine the relationship between epithelial polarity and polarised secretion using custom-built, superresolution microscopes, so that we can image vesicles targeted for apical or basal secretion that are too small to see using conventional systems. Almost all well-characterised epithelia are secretory and little is known about the polarity of absorptive epithelia, where the main direction of transcellular transport is reversed. We have found that the absorptive enterocytes of the adult midgut rely on different polarity factors from secretory epithelia. Midgut cells have an inverted arrangement of intercellular junctions compared to the follicle cells, making them more similar to mammalian epithelia. We are therefore using the gut as a model to discover and analyse new polarity factors and pathways. Another major goal of the group is to understand how the Drosophila oocyte is polarised to define the anterior-posterior axis of the embryo. This requires the microtubule-dependent transport of bicoid and oskar 34 THE GURDON INSTITUTE mRNAs to opposite ends of this very large cell, and we use a range of live imaging techniques to visualise moving mRNAs and growing microtubules in wildtype and mutant oocytes. Selected publications: • Lowe N, St Johnston D et al (2014) Analysis of the expression patterns, subcellular localisations and interaction partners of Drosophila proteins using a pigP protein trap library. Development 141, 3994-4005 Fig 1. Tracks of growing microtubules on the apical side of the follicular epithelium over a two-minute period • Morais-de-Sa E, Mukherjee A, Lowe N and St Johnston D (2014) Slmb antagonises the aPKC/Par-6 complex to control oocyte and epithelial polarity. Development 141, 2984-2992 Fig 2. A clone of mutant follicle cells (marked by the loss of nuclear GFP) that have lost their apical-basal polarity and been extruded from the epithelium. Fig 3. An egg chamber containing two types of follicle cell clones homozygous for mutations that delay the switch between proliferation and differentiation. One class of clones is marked by the loss GFP (green), the other by the loss of RFP (red) and the nuclei have been counterstained for DNA (blue). The two mutations are additive as the cells in the double mutant clones (blue only) are smaller than either single mutant. • Gardiol A and St Johnston D (2014) Staufen targets coracle mRNA to Drosophila neuromuscular junctions and regulates GluRIIA synaptic accumulation and bouton number. Developmental Biology 392, 153-167 • Bergstralh D T and St Johnston D (2014) Spindle orientation: what if it goes wrong? Seminars in Cell & Developmental Biology 34, 140-145 • Morais-de-Sa E, Vega-Rioja A, Trovisco V, St Johnston D (2013) Oskar is targeted for degradation by the sequential action of Par-1, GSK-3, and the SCF-Slimb ubiquitin ligase. Developmental Cell 26: 303-314 Fig 4. A model showing the polarity factors that mark different cortical domains in epithelial cells and the inhibitory interactions between them. Fig 5. A stage 10 egg chamber expressing a marker for the microtubule minus ends fused to Cherry fluorescent protein (red), counterstained for DNA (blue). The minus ends of the microtubules are anchored to the anterior cortex of the oocyte and direct the localisation of bicoid mRNA. THE GURDON INSTITUTE 35 Azim Surani Germline - specification and programming for totipotency and development Co-workers: Delphine Cougot, Dang Vinh Do, Lynn Froggett, Wolfram Gruhn, Ufük Günesdogan, Jamie Hackett, Yun Huang, Naoko Irie, Elena Itskovich, Shinseog Kim, Toshihiro Kobayashi, Caroline Lee, Roopsha Sengupta, Walfred Tang, Thor Theunissen, Julia Tischler, Jan Zylicz Specification of primordial germ cells (PGCs) occurs after the development of equipotent post implantation epiblast cells, which also give rise to all the somatic cells in mice. Recent studies show that that BLIMP1, PRDM14 and AP2g are necessary and sufficient for PGC specification (Fig 1). This mutually interdependent tripartite genetic network initiates PGC specification by repressing the somatic programme but induces pluripotency genes and the germ cell programme (Fig 2). These events can be captured in vitro under specific conditions after they undergo priming and gain competence for the specification of cell fates. The network also initiates sequential and dynamic changes in histone modifications, reactivation of the X chromosome and comprehensive global DNA demethylation, including imprints erasure (Fig 3). The latter is important for the initiation of the imprinting cycle in the germ line, and subsequently, establishment of parent of origin specific imprints (Fig 4). The inheritance of these epigenetic modifications after fertilisation results in functional differences between parental genomes, which following fertilisation is critical for the establishment of totipotency. We are interested in the wider applications of the knowledge gained from the specification of PGCs and epigenetic reprogramming for the manipulation of pluripotent state and cell fates Selected publications: • Irie N, Weinberger L, Tang WWC, Kobayashi T, Viukov S, Manor Y, Dietmann S, Hanna JH and Surani MA (2015) SOX17 is a critical specifier of human primordial germ cell fate. Cell 160, 253-268 • Kim S, Günesdogan U, Zylicz JJ, Hackett JA, Cougot D, Bao S, Lee C, Dietmann S, Allen GE, Sengupta R and Surani MA (2014) PRMT5 protects genomic integrity during global DNA demethylation in primordial germ cells and preimplantation embryos. Molecular Cell 56(4) 564-579 Fig 2a. Differential occupancy and combinatorial roles of BLIMP1, PRDM14 and AP2g : BLIMP1 occupies promoters, PRDM14, distal regulatory elements and AP2g bind both. Venn diagram depicts genes bound by the three factors Fig 1. Founder population of PGCs at E7.5 detected by STELLA. • Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA and Surani MA (2013) Germline DNA demethylation dynamics and imprint erasure through 5-hydoxymethylcytosine. Science 339, 448-452 Fig 2b. The tripartite genetic network regulates expression of genes at PGC specification • Magnüsdöttir E, Dietmann S, Murakami K, Günesdogan U, Tang F, Bao S, Diamanti E, Lao K, Gottgens B, Surani MA (2013) A tripartite transcription factor network regulates primordial germ cell specification in mice. Nature Cell Biology 15, 906-915 Fig 3. Parallel routes to reprograming and the establishment of the epigenetic ground state in primordial germ cells Fig 4. Germline – Imprinting cycle generates the totipotent/ pluripotent states with parent of origin specific DNA methylation imprints for the transmission of epigenetic information. 36 THE GURDON INSTITUTE THE GURDON INSTITUTE 37 Philip Zegerman The regulation of DNA replication initiation in eukaryotes Co-workers: Geylani Can, Clara Collart, Vincent Gaggioli, Christine Hänni, Mark Johnson, Barbara Schöpf To successfully pass on their genetic information, every organism must make a perfect duplicate of their genome in every cell cycle. Failure to copy every chromosome faithfully leads to genomic instability, which is the root cause of cancer. As a result, the process of DNA replication must be strictly regulated, within the normal cell cycle, after DNA damage and during development. Our research takes advantage of a wide variety of organisms to understand the molecular mechanism of how this strict regulation of DNA replication is achieved. Perfect genome duplication in eukaryotes is achieved by coupling the assembly of the DNA replication apparatus with the cell cycle. The fundamental regulator of the cell cycle, Cyclin-Dependent Kinase (CDK) plays a pivotal role in ensuring that replication initiation can only occur once before cell division. We have previously shown that CDK phosphorylates the two essential replication initiation factors Sld2 and Sld3, which in turn allows binding to another essential initiation factor called Dpb11. How CDK phosphorylation of these targets facilitates replication initiation is not known, but the transient association of these factors at origins produces a switch that only allows replication initiation in S-phase of the cell cycle. Interestingly, the time it takes to copy the genome changes during development. For example in many organisms S-phase is fast in the embryo, but greatly slows down in somatic cells. We have shown that it is the level of the key CDK targets that determines the rate of genome duplication in early vertebrate embryogenesis. Our work has therefore pinpointed a fundamental step in replication initiation that determines both the fidelity and the rate of DNA replication across eukaryotes. Selected publications: • Gaggioli V, Zeiser E, Rivers D, Bradshaw CR, Ahringer J and Zegerman P (2014) CDK phosphorylation of SLD-2 is required for replication initiation and germline development in C. elegans. J Cell Biol 204, 507-522 Replication initiation must be strictly controlled to occur once, and only once, in every cell cycle. • Collart C, Allen GE, Bradshaw CR, Smith JC and Zegerman P (2013) Titration of four replication factors is essential for the Xenopus laevis midblastula transition. Science doi:10.1126/science.1241530 • Mantiero D, Mackenzie A, Donaldson A and Zegerman P (2011) Limiting factors execute the temporal programme of origin firing in budding yeast. EMBO J 23, 4805-4814 • Zegerman P and Diffley JF (2010) Checkpoint dependent inhibition of DNA replication initiation via phosphorylation of Sld3 and Dbf4. Nature 467, 474-478 • Zegerman P and Diffley JF (2007) Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature 445, 281-285 Xenopus laevis embryos at the Midblastula Transition. Left is a normal embryo, right is an embryo over-expressing limiting replication factors. The sequence of eukaryotic replication initiation Phospho-peptide array analysis of replication initiation factors. 38 THE GURDON INSTITUTE THE GURDON INSTITUTE 39 Magdalena Zernicka-Goetz Developmental plasticity, fate and morphogenesis in the mouse embryo Relocated: The Zernicka-Goetz Group are now located in the Department of Physiology, Development and Neuroscience, University of Cambridge. We investigate mechanisms underlying the specification of cell fate and patterning using mouse embryos as our major model because this allows us to combine cell biological and molecular genetic approaches with live imaging in a system that is close to human development. Plasticity and Cell Fate acquisition: Embryonic cells in mouse and human are flexible and how their fate becomes restricted is unclear. To determine the molecular steps that mediate the transition from the egg totipotency towards either differentiation or pluripotency, we have isolated a number of regulatory genes essential for lineage determination and follow the interplay between cell polarity, position and developmental history of cells on fate specification. Asymmetric and Symmetric divisions: Development begins with the asymmetric divisions of the oocyte, following fertilisation cells divide symmetrically until the 8-cell stage when division asymmetry is again important. To understand the processes that break symmetry, we study the events that lead to cell polarisation and spindle orientation. Maternal to Zygotic Transition: To understand the factors essential for the correct development, we have established a non-invasive method to forecast already at fertilisation which eggs have the highest chance of development to birth. We collaborate with IVF clinics to select with this approach the best quality eggs for transfer to would-be-mothers. Self-organisation of pattern: We wish to understand how embryo integrates the development of different cell types into an organism. To address this, we have developed in vitro system to culture and image development at implantation stages outside the mother and to mimic several of the key morphogenetic steps using ES cells. 40 THE GURDON INSTITUTE Selected publications: • Graham SJ, Wicher KB, Jedrusik A, Guo G, Herath W, Robson P and Zernicka-Goetz M (2014) BMP signalling regulates the pre-implantation development of extraembryonic cell lineages in the mouse embryo. Nature Comm 5: 5667 • Bedzhov I, Leung CY, Bialecka M and Zernicka-Goetz M. (2014) In vitro culture of mouse blastocysts beyond the implantation stages. Nature Protocols 9(12): 2732-9 • Bedzhov I and Zernicka-Goetz M (2014) Selforganizing properties of mouse pluripotent cells initiate morphogenesis upon implantation. Cell 156(5):1032-44. • Coelho PA, Bury L, Sharif B, Riparbelli MG, Callaini G, Glover DM and Zernicka-Goetz M (2013) Spindle formation in the mouse embryo requires plk4 in the absence of centrioles. Dev Cell 27(5): 586-97 • Leung CY and Zernicka-Goetz M (2013) Angiomotin prevents pluripotent lineage differentiation in mouse embryos via Hippo pathway-dependent and -independent mechanisms. Nature Comm 2013, 4: 2251 Mouse embryo before implantation - trophectoderm in blue and pluripotent cells in different colours. (Image: CY Leung) Mouse embryo rosette at the time of implantation”. Nuclei in blue, membranes in red and apical marker in yellow. THE GURDON INSTITUTE 41 CATEGORIES OF APPOINTMENT / SENIOR GROUP LEADERS CATEGORIES OF APPOINTMENT SENIOR GROUP LEADER Professor, Director of Research or Reader GROUP LEADER 5-year grant-funded appointment (maximum 10 years) CAREER DEVELOPMENT FELLOW 4-year grant-funded appointment SENIOR RESEARCH ASSOCIATE Grant-funded appointment within individual groups RESEARCH ASSOCIATE/FELLOW Postdoctoral Fellow within individual groups, appointed or invited by group leader RESEARCH ASSISTANT Postgraduate within individual groups, mainly grantfunded GRADUATE STUDENT 3 or 4 year studentship within individual groups, mainly grant-funded RESEARCH TECHNICIAN Within individual groups, mainly grant-funded LABORATORY ASSISTANT / TECHNICIAN Within individual groups or part of core support, grant-funded ITALICS: LEAVERS DURING 2014 POSTGRADUATE OPPORTUNITIES As part of the University of Cambridge, the Institute welcomes enquiries from prospective graduate students. We have a thriving population of graduates who contribute greatly, not only to the stimulating research environment, but also to the life of the Institute as a whole. Additionally, graduates become members of the biological or medical sciences department to which their group is affiliated. Graduate studentships are supported mainly by the Wellcome Trust or Cancer Research UK but additional sponsorship may be solicited from a variety of sources, including government research councils. Applicants should write, in the first instance, to the leader of the group they wish to join. 42 THE GURDON INSTITUTE DANIEL ST JOHNSTON PhD FRS FMedSci, Director Wellcome Trust Principal Research Fellow Professor of Developmental Genetics Member, European Molecular Biology Organization Director, Company of Biologists (Member of the Department of Genetics) DAN BERGSTRALH PhD Wellcome Trust Research Associate CATIA ALEXANDRA CARVALHO MENDES PhD Student JIA CHEN PhD Royal Society KC Wong Fellow NICOLE DAWNEY BSc Wellcome Trust Research Assistant HÉLÈNE DOERFLINGER PhD Wellcome Trust Research Associate/Institute Outreach Officer ARTUR FERNANDES MPhil School of Biological Sciences PhD Student WERONIKA FIC PhD Wellcome Trust Research Associate TIMM HAACK PhD Wellcome Trust Developmental Biology PhD Student JACKIE HALL MSc Wellcome Trust Senior Research Technician HOLLY LOVEGROVE MSc Herchel Smith PhD Student NICK LOWE PhD Wellcome Trust Research Associate AVIK MUKHERJEE MSc CISS PhD Student DMITRY NASHCHEKIN PhD Wellcome Trust Research Associate JENNIFER RICHENS PhD Wellcome Trust Research Associate ARAM SAYADIAN MPhil Wellcome Trust PhD Student (Formerly Wellcome Trust Developmental Biology PhD Student) GEORGE SIRINAKIS PhD Wellcome Trust Senior Research Associate VANESSA STEFANAK PhD Administration Manager for the Office of the Director SENIOR GROUP LEADERS VITOR TROVISCO PhD Wellcome Trust Research Associate HELEN ZENNER-BRANCO PhD Wellcome Trust Research Associate JULIE AHRINGER PhD FMedSci Professor of Genetics and Genomics Wellcome Trust Senior Research Fellow Member, European Molecular Biology Organization (Member of the Department of Genetics) ALEX APPERT PhD Wellcome Trust Research Associate DARYA AUSIANNIKAVA BSc Darwin Trust PhD Student FANÉLIE BAUER PhD Herchel Smith Fellow RON CHEN PhD Wellcome Trust Senior Research Associate MIKE CHESNEY PhD Wellcome Trust Research Associate YAN DONG MSc Wellcome Trust Research Associate KENNETH EVANS PhD Wellcome Trust Research Associate CSENGE GAL PhD Wellcome Trust Research Associate CAROLINA GEMMA PhD Wellcome Trust Research Associate MORITZ HERRMANN BSc BBSRC PhD Student JÜRGEN JÄNES MSc Wellcome Trust Mathematical Biology PhD Student DJEM KISSIOV BA Wellcome Trust Research Assistant ALICIA McMURCHY PhD CIHR Research Associate JOSANA RODRIGUEZ PhD Wellcome Trust Research Associate WEI QIANG SEOW BSc A*STAR PhD Student PRZEMYSLAW STEMPOR PhD Wellcome Trust Research Associate ANNETTE STEWARD BSc Wellcome Trust Research Assistant CHRISTINE TURNER PA/Secretary CARSON WOODBURY BA Thouron Scholarship MPhil Student BRIAN WYSOLMERSKI BA Biology MPhil Student EVA ZEISER BSc Wellcome Trust Research Assistant ANDREA BRAND PhD FRS FMedSci Herchel Smith Professor of Molecular Biology Head of Wellcome Trust Labs Wellcome Trust Senior Investigator Member of Council, The Royal Society Member, European Molecular Biology Organization (Member of the Department of Physiology, Development and Neuroscience) JANINA ANDER BSc BBSRC PhD Student JOSEPHINE BAGERITZ PhD Wellcome Trust Research Associate ELIZABETH CAYGILL PhD BBSRC Research Associate SETH CHEETHAM BSc Herchel Smith PhD Student ESTEBAN CONTRERAS SEPULVEDA PhD Wellcome Trust Developmental Biology PhD Student MELANIE CRANSTON BA BBSRC Research Assistant ABHIJIT DAS PhD Wellcome Trust Research Associate CATHERINE DAVIDSON BSc BBSRC Research Associate PAUL FOX PhD Wellcome Trust Research Associate KATRINA GOLD PhD Wellcome Trust Research Associate (Formerly Wellcome Trust Developmental Biology PhD Student) ANNA HAKES MPhil Wellcome Trust Developmental Biology PhD Student JUN LIU BA Dr Herchel Smith Graduate Fellow OWEN MARSHALL PhD BBSRC Research Associate LEO OTSUKI MPhil Wellcome Trust Developmental Biology PhD Student CHLOE SHARD BSc Australia Trust/McCrum PhD Student TONY SOUTHALL PhD Wellcome Trust Research Associate PAULINE SPÉDER PhD Wellcome Trust Research Associate CHRISTINE TURNER PA/Secretary JELLE VAN DEN AMEELE MD PhD Wellcome Trust Research Associate MO ZHAO BSc Chinese Scholarship Council PhD Student NICK BROWN PhD Professor of Cell Biology Member, European Molecular Biology Organization (Member of the Department of Physiology, Development and Neuroscience) NATALIA BULGAKOVA PhD BBSRC Research Associate JUAN MANUEL GOMEZ PhD BBSRC Reseach Associate HANNAH GREEN MPhil Wellcome Trust Developmental Biology PhD Student ANNABEL GRIFFITHS BA MRC PhD Student SVEN HUELSMANN PhD University of Jyväskulä Research Associate BENJAMIN KLAPHOLZ PhD BBSRC Research Associate TARUN KUMAR BSc Commonwealth PhD Student MIRANDA LANDGRAF MA PA/Secretary AIDAN MAARTENS PhD BBSRC Research Associate JOHN OVERTON HNC Wellcome Trust/BBSRC Chief Research Technician PAULA RODRIGUEZ SANCHEZ MSc Wellcome Trust Research Assistant PEERAPAT THONGNUEK MRes Thai Government PhD Student JOHN GURDON Kt DPhil DSc FRS Distinguished Group Leader Nobel Laureate in Physiology or Medicine 2012 Wellcome Trust Senior Investigator Foreign Associate, US National Academy of Sciences Foreign Associate, US National Academy of Sciences Institute of Medicine Foreign Associate, French National Academy of Sciences Member, European Molecular Biology Organization Member, Academia Europaea Honorary Fellow, Royal College of Physicians Honorary Member of American Anatomical Society Honorary Member of Anatomical Society of Great Britain Honorary Fellow UK Academy of Medical Sciences (Member of the Department of Zoology) DILLY BRADFORD PA/Secretary NIGEL GARRETT HNC Wellcome Trust Research Assistant RICHARD HALLEY-STOTT PhD MRC Research Associate EVA HÖRMANSEDER PhD EMBO Research Fellow JEROME JULLIEN PhD Wellcome Trust Research Associate MAGDALENA KOZIOL PhD Isaac Newton Trust/Wellcome Trust Research Associate KEI MIYAMOTO PhD Herchel Smith Research Associate MAMI OIKAWA PhD MRC Research Associate ANGELA SIMEONE PhD Wellcome Trust/MRC Research Associate (Bioinformatics) MARTA TEPEREK-TKACZ MSc Wellcome Trust Developmental Biology PhD Student/MRC Research Assistant MUNENDER VODNALA PhD Swedish Society for Medical Research (SSMF) Fellow STAN WANG BS NIH/Gates MD-PhD Student MING-HSUAN WEN MSc Taiwan Government PhD Student THE GURDON INSTITUTE 43 SENIOR GROUP LEADERS STEVE JACKSON PhD FRS FMedSci Frederick James Quick Professor of Biology Head of Cancer Research UK Labs Member, European Molecular Biology Organization ERC Advanced Researcher Associate Faculty Member of the Wellcome Trust Sanger Institute (Member of the Department of Biochemistry) PALLAVI AGARWAL PhD Cancer Research UK Research Associate GABRIEL BALMUS DVM PhD Cancer Research UK Research Associate LINDA BASKCOMB MSc Cancer Research UK Senior Chief Research Laboratory Technician RIMMA BELOTSERKOVSKAYA PhD Cancer Research UK Research Associate ANDREW BLACKFORD PhD Cancer Research UK Research Associate JESSICA BROWN MB Bchir Wellcome Trust Clinical Fellow/PhD Student TING-WEI (Will) CHIANG MSc Cambridge Overseas Trust PhD Student JULIA COATES MA Cancer Research UK Research Assistant MATTHEW CORNWELL MChem Dept Chemistry/Cambridge Cancer Centre/School of Physical Sciences PhD Student MUKERREM DEMIR BSc ERC Senior Research Technician KATE DRY PhD Cancer Research UK Information Specialist JOSEP FORMENT PhD A-T Society/Cancer Research UK Research Associate YARON GALANTY PhD ERC Senior Research Associate NICOLA GEISLER BSc Wellcome Trust Chief Research Technician MAREIKE HERZOG BA Wellcome Trust PhD Student (joint with Sanger Institute) SATPAL JHUJH MSc ERC Research Technician DELPHINE LARRIEU PhD Cancer Research UK/MRC Research Associate CARLOS LE SAGE PhD ERC Research Associate 44 THE GURDON INSTITUTE SENIOR GROUP LEADERS NATALIA LUKASHCHUK PhD Cancer Research UK Research Associate FRANCISCO MUNOZ MARTINEZ PhD Marie Curie Research Intra-European Fellow RYOTARO NISHI PhD Cancer Research UK Research Associate FABIO PUDDU PhD EMBO Fellow/EU Research Associate HELEN REED PA/Secretary ISRAEL SALGUERO CORBACHO PhD Wellcome Trust Research Associate CHRISTINE SCHMIDT PhD ERC Research Associate MATYLDA SCZANIECKA-CLIFT PhD ERC Research Associate ROHAN SIVAPALAN BSc EU Research Assistant/BBSRC/Horizon PhD Student JON TRAVERS PhD EU Research Associate DAVID WEISMANN PhD EMBO Research Fellow PAUL WIJNHOVEN BSc Cancer Research UK Research Assistant/PhD Student TONY KOUZARIDES PhD FRS FMedSci Deputy Director Professor of Cancer Biology Cancer Research UK Gibb Fellow Member, European Molecular Biology Organization ERC Advanced Researcher (Member of the Department of Pathology) ANDREJ ALENDAR MSc Cancer Research UK Research Assistant PAULO AMARAL PhD ERC Research Associate ANDREW BANNISTER PhD Cancer Research UK Senior Research Associate, Senior Radiation Protection Supervisor ISAIA BARBIERI PhD Leukaemia & Lymphoma Research Research Associate ESTER CANNIZZARO MSc Cancer Research UK PhD Student KA HING CHE PhD Cancer Research UK Research Associate MARIA CHRISTOPHOROU PhD Cancer Research UK Research Associate ALISTAIR COOK GIBiol ERC Chief Research Technician CHUN YEW FONG MBBS BMedSci Visiting Leukaemia Foundation of Australia/ Haematology Society of Australia & New Zealand/Royal Australasian College of Physicians Clinical Fellow NAMSHIK HAN PhD ERC Research Associate (Bioinformatics) SRI LESTARI MSc Cancer Research UK Senior Research Laboratory Technician NIKKI MANN BA PA/Secretary VALENTINA MIGLIORI PhD EMBO Fellow/King’s College Junior Research Fellow GONZALO MILLAN ZAMBRANO PhD BBSRC Research Associate JESSICA MORISON PhD Visiting Researcher SAM ROBSON PhD ERC Research Associate (Bioinformatics) HELENA SANTOS ROSA PhD Cancer Research UK Senior Research Associate PETER TESSARZ PhD Cancer Research UK/BBSRC Research Associate EMMANUELLE VIRÉ PhD ERC/Cancer Research UK Research Associate MEIKE WIESE MSc Cancer Research UK PhD Student BEATA WYSPIANSKA MSc BBSRC Case PhD Student RICK LIVESEY MB BChir PhD Wellcome Trust Senior Investigator University Reader in Molecular Neuroscience (Member of the Department of Biochemistry) SIAN ALEXANDER DPhil MRCP Visiting Academic Clinical Fellow HOZEFA AMIJEE PhD MRC Research Associate PHILIPP BERG MRes Wellcome Trust PhD Student LAURA BRIGHTMAN BA Stem Cell Centre Seed Funding Research Assistant PHILIP BROWNJOHN PhD Alzheimer’s Research UK Research Associate TATYANA DIAS PhD Alzheimer’s Research UK Research Associate LEWIS EVANS PhD Wellcome Trust Research Associate JAYNE FISHER PA/Secretary ALBERTO FRANGINI PhD Wellcome Trust Research Associate PETER KIRWAN PhD MRC Research Associate (Formerly Wellcome Trust Development Biology PhD Student) TERESA KRIEGER MSci EPSRC PhD Student (Joint with Ben Simons) AMELIA McGLADE BSc Innovative Medicines Initiative Research Assistant AYIBA MOMOH MSc Wellcome Trust Research Assistant STEVEN MOORE PhD Wellcome Trust Research Associate TOMOKI OTANI MPhil Wellcome Trust Developmental Biology PhD Student MANUEL PETER PhD Innovative Medicines Initiative Research Associate NATHALIE SAURAT BSc Woolf Fisher PhD Student/ARUK Research Associate JAMES SMITH BSc Innovative Medicines Initiative Research Associate VICTORIA STUBBS PhD Innovative Medicines Initiative Research Assistant ERIC MISKA PhD Herchel Smith Professor of Molecular Genetics Wellcome Trust Senior Investigator Cancer Research UK Senior Research Fellow Wellcome Trust Sanger Institute Affiliated Faculty Member Member, European Molecular Biology Organization ERC Independent Starting Researcher (Member of the Department of Genetics) ALPER AKAY PhD Cancer Research UK Research Associate ALYSON ASHE PhD Herchel Smith Postdoctoral Fellowship FABIAN BRAUKMANN MSc ERC Research Assistant/PhD Student AMY CORDING BSc Cancer Research UK Research Assistant TOMAS di DOMENICO PhD ERC Research Associate (Bioinformatics) TANAY GHOSH PhD ERC/Cancer Research UK Research Associate SABRINA HUBER MSc Cambridge PhD Training Programme in Chemical Biology and Molecular Medicine JOANNA KOSALKA MPhil Wellcome Trust Developmental Biology PhD Student MIRANDA LANDGRAF MA PA/Secretary JÉREMIE LE PEN MPhil Wellcome Trust Developmental Biology/ERC PhD Student MILAN MALINSKY MPhil Wellcome Trust Mathematical Biology PhD Student EYAL MAORI PhD Herchel Smith Research Associate RAGINI MEDHI BSTech MPhil Student SYLVIANE MOSS PhD Cancer Research UK Research Associate/Lab Manager KENNETH MURFITT MPhil ERC PhD Student (Formerly Wellcome Trust Development Biology PhD Student) MARC RIDYARD PhD Cancer Research UK Lab Manager ALEXANDRA SAPETSCHNIG PhD ERC Senior Research Associate (formerly PETER SARKIES PhD Gonville and Caius Research Fellow/CRUK Research Associate MÉLANIE TANGUY PhD Cancer Research UK Research Associate EVA-MARIA WEICK PhD ERC PhD Student/Research Associate JONATHON PINES PhD FMEDSci Director of Research in Cell Division Cancer Research UK Senior Research Fellow Member, European Molecular Biology Organization (Member of the Department of Zoology) PHILIPPE COLLIN PhD BBSRC Research Associate BARBARA DI FIORE PhD Cancer Research UK Research Associate ANJA HAGTING PhD Cancer Research UK Research Associate, Biological Safety Officer ANDREW HARRISON PhD MRC Research Associate DAISUKE IZAWA PhD Cancer Research UK/MRC Research Associate MARK JACKMAN PhD Cancer Research UK Research Associate, Chemical Safety Officer AGATA LICHAWSKA PhD Herchel Smith PhD Student CHIARA MARCOZZI MSc Boehringer Ingelheim/BBSRC PhD Student TAKAHIRO MATSUSAKA PhD Cancer Research UK Research Associate OXANA NASHCHEKINA MSc Cancer Research UK Chief Research Technician BERNHARD STRAUSS PhD MRC Research Associate JILL TEMPLE MSc MRC Research Assistant SAMUEL WIESER MSc Liechtenstein Government PhD Student/ MRC Research Assistant CLAUDIA WURZENBERGER PhD Marie Cure Research Intra-European Fellow KEIKO YATA PhD MRC Research Associate THE GURDON INSTITUTE 45 SENIOR GROUP LEADERS / GROUP LEADERS AZIM SURANI PhD CBE FRS FMEDSci Director of Germline and Epigenomics Research Wellcome Trust Senior Investigator Member, European Molecular Biology Organization Member Academia Europaea Associate Fellow, Third World Academy of Sciences (Member of the Department of Physiology, Development and Neuroscience) DELPHINE COUGOT PhD Wellcome Trust Research Associate DANG VINH DO PhD Wellcome Trust Research Associate LYNN FROGGETT PA/Secretary WOLFRAM GRUHN PhD Wellcome Trust Research Associate/EMBO Research Fellow UFUK GÜNESDOGAN PhD Marie Curie Intra-European Fellow JAMIE HACKETT PhD HFSP Research Associate YUN HUANG BA MB-PhD Student NAOKO IRIE PhD BIRAX Research Associate ELENA ITSKOVICH MSc Wellcome Trust PhD Student SHINSEOG KIM PhD Wellcome Trust Research Associate TOSHIHIRO KOBAYASHI PhD JSPS Fellow CAROLINE LEE ONC Wellcome Trust Chief Research Technician, Radiation Protection Supervisor CAROL READHEAD PhD Visiting Academic ROOPSHA SENGUPTA PhD Wellcome Trust Research Associate WALFRED TANG MPhil Croucher Cambridge International PhD Student THOR THEUNISSEN PhD Sir Henry Wellcome Postdoctoral Fellow (Based at Whitehead Institute, Boston, US) 46 THE GURDON INSTITUTE JULIA TISCHLER PhD APART Research Fellow JAN ZYLICZ MSc Wellcome Trust PhD Student JENNIFER GALLOP PhD Wellcome Trust Research Career Development Fellow ERC Independent Starting Researcher (Member of the Department of Biochemistry) GUILHERME CORREIA MSc Wellcome Trust PhD Student HELEN FOX MPhil Wellcome Trust Developmental Biology PhD Student LYNN FROGGETT PA/Secretary YOSHIKO INOUE PhD Wellcome Trust/ERC Research Associate IRIS JARSCH PhD Wellcome Trust Research Associate JULIA MASON BSc ERC Research Assistant DANIEL SAXTON BSc ERC Research Assistant HANAE SHIMO MSc Funai Foundation PhD Student ASTRID WALRANT PhD ERC Research Associate MERITXELL HUCH PhD Wellcome Trust Sir Henry Dale Fellow Beit Prize Fellow (Member of the Department of Physiology, Development and Neuroscience) LUIGI ALOIA PhD Wellcome Trust Research Associate JOHN CRANG DPhil PA/Secretary CHRISTOPHER HINDLEY PhD SCI Seed Funding Research Associate GIANMARCO MASTROGIOVANNI MSc Marie Curie Initial Training Network PhD Student MIKEL McKIE MSci Wellcome Trust Research Assistant ALESSANDRA MERENDA MSc Marie Curie Initial Training Network PhD Student GROUP LEADERS / VISITING STUDENTS & RESEARCHERS EUGENIA PIDDINI PhD Royal Society Research Fellow (Member of the Department of Zoology) MICHAEL DINAN MPhil Wellcome Trust Developmental Biology PhD Student MAJA GOSCHORSKA MPhil Cambridge Cancer Centre PhD Student LEA HAMPTON-O’NEIL BSc MPhil Student GOLNAR KOLAHGAR PhD Cancer Research UK Research Associate KASIA KOZYRSKA MSc PhD Student IWO KUCINSKI MPhil Wellcome Trust Developmental Biology PhD Student KATHY OSWALD MA PA/Secretary SASKIA SUIJKERBUIJK PhD Rubicon Research Associate SILVIA VIVARELLI PhD Cancer Research UK Research Associate LAURA WAGSTAFF PhD Cancer Research UK Research Associate EMMA RAWLINS PhD MRC Research Fellow (Member of the Department of Pathology) GAYAN BALASOORIYA MSc MRC Research Technician/PhD Student CHRISTOPH BUDJAN MPhil Wellcome Trust Developmental Biology PhD Student ANGELENE HUFFMAN PA/Secretary JO-ANNE JOHNSON MB ChB MRCPCH Wellcome Trust Clinical Fellow/PhD Student USUA LARESGOITI GARAY PhD Wellcome Trust Research Associate MARKO NIKOLIC MA MB BChir MRCP Wellcome Trust Clinical Fellow/PhD Student CHANDRIKA RAO MSc March of Dimes/Wellcome Trust Chief Research Technician PHILIP ZEGERMAN PhD Worldwide Cancer Research International Research Fellow (Member of the Department of Biochemistry) GEYLANI CAN MSc Turkish Government/Sackler PhD Student CLARA COLLART PhD Collaborating Researcher from Professor Jim Smith’s lab, MRC NIMR, London VINCENT GAGGIOLI PhD Worldwide Cancer Research Research Associate CHRISTINE HÄNNI MSc Cambridge Cancer Centre PhD Student ANGELENE HUFFMAN PA/Secretary MARK JOHNSON PhD Worldwide Cancer Research Research Associate OLEG KOVALEVSKIY PhD Cancer Research UK Research Associate BARBARA SCHÖPF PhD Worldwide Cancer Research Research Associate MAGDALENA ZERNICKA-GOETZ PhD Wellcome Trust Senior Research Fellow Professor of Developmental Biology Member, European Molecular Biology Organization (Member of the Department of Physiology, Development and Neuroscience) FRANCESCO ANTONICA PhD Wellcome Trust Research Associate PAULA ALMEIDA COELHO PhD Visiting Academic IVAN BEDZHOV PhD Wellcome Trust Research Associate MONIKA BIALECKA PhD Wellcome Trust Research Associate LEAH BURY Diplom Mol Med Cambridge Cancer Centre PhD Student ANDY COX PhD Wellcome Trust Research Assistant JOHN CRANG DPhil PA/SECRETARY MOHAMMED GOOLAM MSc St John’s College Mary Gray PhD Student SARAH GRAHAM MSc PhD Student AGNIESZKA JEDRUSIK PhD Wellcome Trust Research Associate (Formerly Wellcome Trust Developmental Biology PhD Student) CHUEN YAN LEUNG BSc PhD Student MARYNA PANAMAROVA BSc Darwin Trust PhD Student GAELLE RECHER PhD Wellcome Trust Research Associate MARTA SHAHBAZI ALONSO PhD Wellcome Trust Research Associate BEN SIMONS PhD Herchel Smith Professor of Physics Cavendish Laboratory EDOUARD HANNEZO PhD Postdoctoral Researcher TERESA KRIEGER BA MSci EPSRC PhD Student (Joint with Rick Livesey) STEFFEN RULANDS PhD Postdoctoral Researcher VISITING STUDENTS/RESEARCHERS LYNN ASANTE-ASARE Biochemical Society Vacation Student, University of Warwick (Jackson Lab) ROBERTA AZZARELLI Collaborating Researcher, Hutchison MRC Research Centre (Huch Lab) ADAM BENABID BSc Visiting Master’s Student, École Normale Supérieure, Paris, France (Piddini Lab) LUKE BIBBY University of Cambridge Vacation Student (Pines Lab) GINA BLAKE Wellcome Trust Developmental Biology PhD Rotation Student (Rawlins Lab) DANIEL BROOK University of Cambridge Part III Student (Gallop Lab) CALIN CAUACEAN University of Cambridge Part II Student (Pines Lab) AMY DANSEN University of Cambridge Part II Student (Livesey Lab) ALFONSA DIAZ TORRES Visiting PhD Student, Universidad Pablo Olavide, Seville, Spain (Brand Lab) ANA DOMINGUEZ PÉREZ Vacation Student from University of Navarra, Spain (Brown Lab) EMILY DUDGEN University of Cambridge Part II Student (Piddini Lab) EMILY FALDON University of Cambridge Part II Student (Brown Lab) KIRSTY FERGUSON University of Cambridge Part III Student (Livesey Lab) HELENA FRANCIS University of Cambridge Part III Student (St Johnston Lab) MARCOS GALLEGO LLORENTE BBSRC Rotation PhD Student (Brand Lab) ANA GASOL GARCIA Visiting Master’s Student, Vrije University, Amsterdam, Netherlands (Piddini Lab) ZAMIRA GUERRA SOARES Visiting PhD Student, UFMG, Brazil (Miska Lab) ROSANNA HANCOCK University of Cambridge Part II Student (Zernicka-Goetz Lab) OLIVIA HARRIS Wellcome Trust Rotation PhD Student (Stem Cell, Huch Lab) SARAH HERBERG BSc Visiting Master’s Erasmus Student, University of Bayreuth (Gurdon Lab) EVA HIGGINBOTHAM Wellcome Trust Developmental Biology Rotation PhD Student (Surani Lab) ISABEL JOHNSON Visiting Student, University of Wisconsin, USA (Ahringer Lab) BARANSEL KAMAZ Dr Hadwen Trust Vacation Student, Hacettepe University, Ankara, Turkey (Huch Lab) CHRISTINE KLEINERT Visiting Erasmus Master’s Student, Potsdam University, Germany (Zegerman Lab) ANNA KONONEN Visiting Erasmus Administrator, University of Jyväskylä, FInland (Administration) BART KRAMER BSc Visiting Master’s Erasmus Student, University of Utrecht, Netherlands (Huch Lab) THE GURDON INSTITUTE 47 VISITING STUDENTS & RESEARCHERS / SUPPORT STAFF RIINA LAMPELA Wellcome Trust Rotation PhD Student (Livesey Lab) ELODIE LE CLECH Vacation Student, Sophia Antipolis University, Nice, France (Rawlins Lab) KATHERINE LEE University of Cambridge Vacation Student (Brand Lab) SANG EUN LEE Visiting Student, Imperial College, London (Huch Lab) JONATHAN LIANG MPhil Student, Computational Biology, University of Cambridge (Ahringer Lab) PING MA PhD Visiting Researcher, University of Georgia, Athens USA (Miska Lab) ALISE MOLOTOVA Amgen Scholar (Gurdon Lab) MATE NASZAI University of Cambridge Part II Student (Rawlins Lab) JOSEPH NELSON University of Cambridge Part II Student (Ahringer Lab) JAMES PICKLES Visiting PhD Student, Northern Institute for Cancer Research, Newcastle University, UK (Jackson Lab) ZOE PILLIDGE BBSRC DTP Rotation Student (Piddini Lab) SARA PRECIADO PhD Visiting Marie Curie Fellow, QMUL, London (Jackson Lab) CONOR REID University of Cambridge Part II Student (St Johnston Lab) TIMO REY University of Cambridge Part II Student (Zegerman Lab) ANDREW RUMBOL University of Cambridge Part III Student (Pines Lab) THOMAS SANFORD University of Cambridge Part III Student (Jackson Lab) LISA SCHUBERT Visiting Master’s Student, University of Heidelberg, Germany (Zegerman Lab) AISHWARYA SIVAKUMAR Vacation Student, University of Pune, India (Jackson Lab) LIOR SODAY University of Cambridge Part III Student (Miska Lab) TERESA TOUDAL KNUDSEN Part II Student (Brown Lab) 48 THE GURDON INSTITUTE DENIS TORRE Visiting Undergraduate Student, Trieste University, Italy (Livesey Lab) BENITA TURNER-BRIDGER Wellcome Trust Developmental Biology Rotation PhD Student (Livesey Lab) ANTOINETTE van OUWERKERK BSc Visiting Master’s Student, University of Leiden, The Netherlands (Surani Lab) GREGOIRE VERNAZ Visiting Master’s Student, University of Zurich, Switzerland (Miska Lab) LOUISE VERON Visiting Master’s Student, ENS Cachan, France (Miska Lab) SAMUEL WATTRUS Vacation Student, Harvard Stem Cell Institute, Mass, USA (Gurdon Lab) STEFANIE WEISS Visiting Master’s Student, Ludwig-Maximilians University, Munich (Miska Lab) LOUISE WHITELEY University of Cambridge Part II Student (Gallop Lab) EMMA WICTOME University of Cambridge Part II Student (Brown Lab) BEVERLEY WILSON University of Cambridge Part II Student (Jackson Lab) NANCY ZHENG University of Cambridge Part II Student (Brand Lab SUPPORT STAFF ADMINISTRATION BIOINFORMATICS TECHNICAL SUPPORT ANN CARTWRIGHT MPhil Institute Administrator SUZANNE CAMPBELL BSc HR/Grants Manager JANE COURSE Accounts Manager DIANE FOSTER Deputy Administrator KATHY HILTON DipMgm CBSG Manager ANGELENE HUFFMAN Receptionist CEZARY KUCEWICZ MA Accounts/Clerical Assistant LYNDA LOCKEY Office Manager JANET MOORE PhD Receptionist SYLVIANE MOSS PhD Specialised Facilities Manager - Biological Safety Officer CHARLES BRADSHAW PhD Bioinformatician GEORGE ALLEN PhD Bioinformatician POLLY ATTLESEY Unit Manager RYAN ASBY MELODIE AVAKIAN BSc LUKE ATTLESEY CAROLINE BLAKE ELEANOR DALE NICOLA EVANS-BAILEY SOPHIE GARNHAM MARK GILLILAND SAMANTHA HANNA BSc RICHARD HARPER JACK HARRIS GILLIAN HYNES BEN JAGGS WEN JIN SHANE JOHNSON THERESE JONES-GREEN BSc URSZULA KOKOT ADAM LAW GRACE LUCAS ASHLEIGH MATTHEWS FALLON MILLER LORRAINE MILLER ZOE MUMFORD RACHEL MURFITT DOMINIC OSBORNE NIGEL PECK JASON RISEBOROUGH HANNAH RULE DAVID SIMPSON DEAN SWINDEN DANIEL WATTS COMPUTING ALASTAIR DOWNIE Computer Systems Manager RICHARD BUTLER PhD Research Associate (Imaging) NICOLA LAWRENCE PhD Computer Imaging Associate, Laser Safety Officer NIGEL SMITH Computer Associate ALEX SOSSICK BSc Computer Imaging Associate, Laser Safety Officer PETER WILLIAMSON BSc Computer Associate ACCOUNTS/PURCHASING/STORES IAN FLEMING Stores/Purchasing Manager SIMON ALDIS Purchasing/Accounts Assistant DAVID COOPER Stores Technician RICHARD ETTERIDGE MA Purchasing/Accounts Assistant ANDY VINCENT Senior Stores Technician MICK WOODROOFE Purchasing/Accounts Assistant COMBINED BUILDINGS SERVICES GROUP (CBSG) CLIVE BENNETT ALAN RIX JOEL SHUBROOKS SIMON WILSON KATHERINE BENNETT STEPHEN SALT PAUL TURRELL MEDIA/GLASS WASHING JUANITA BAKER-HAY Media/Glass Washing Manager SUE HUBBARD Deputy Media/Glass Washing Manager JANIS ABBOTT LISA BAKER KAZUKO COLLINS VINCE DAMS SANDRA HUMAN MARK JOHNS TRACY MITCHELL ZEST CATERING AMANDA HARRIS MELISSA PLOWDEN ROBERTS THE GURDON INSTITUTE 49 INSTITUTE PUBLICATIONS The following is a list of articles by members of the Institute that were either published or accepted for publication, since the date of publication of our last Annual Report. INSTITUTE PUBLICATIONS 8 Baker AM, Cereser B, Melton S, Fletcher AG, Rodriguez-Justo M, Tadrous PJ, Humphries A, Elia G, McDonald SA, Wright NA, Simons BD, Jansen M and Graham TA (2014) Quantification of crypt and stem cell evolution in the normal and neoplastic human colon. Cell Rep 8, 4: 940 – 947 26 Di Domenico T, Potenza E, Walsh I, Parra RG, Giollo M, Minervini G, Piovesan D, Ihsan A, Ferrari C, Kajava AV and Tosatto SC (2014) RepeatsDB: a database of tandem repeat protein structures. Nucleic Acids Res 42, Database issue: D352 – D357 [Miska Group] 27 Forment JV, Flipphi M, Ventura L, González R, Ramón D and Maccabe AP (2014) High-affinity glucose transport in aspergillus nidulans is mediated by the products of two related but differentially expressed genes. PLoS One 9, 4: e94662 [Jackson Group] 28 Frey A, Listovsky T, Guilbaud G, Sarkies P and Sale JE (2014) Histone H3.3 is required to maintain replication fork progression after UV damage. Curr Biol 24, 18: 2195 – 2201 [Miska Group] 1 Ajduk A, Biswas Shivhare S and Zernicka-Goetz M (2014) The basal position of nuclei is one pre-requisite for asymmetric cell divisions in the early mouse embryo. Dev Biol 392, 2: 133 – 140 9 2 Alcolea MP, Greulich P, Wabik A, Frede J, Simons BD and Jones PH (2014) Differentiation imbalance in single oesophageal progenitor cells causes clonal immortalization and field change. Nat Cell Biol 16, 6: 615 – 622 Balmus G and McIntyre RE (2014) Genetic screens in mice for genome integrity maintenance and cancer predisposition. Current Opinion in Genetics and Development 24, 1: 1 – 7 [Jackson Group] 10 3 Ali FR, Cheng K, Kirwan P, Metcalfe S, Livesey FJ, Barker RA and Philpott A (2014) The phosphorylation status of Ascl1 is a key determinant of neuronal differentiation and maturation in vivo and in vitro. Development 141, 11: 2216 – 2224 Barbera M, di Pietro M, Walker E, Brierley C, Macrae S, Simons BD, Jones PH, Stingl J and Fitzgerald RC (2014) The human squamous oesophagus has widespread capacity for clonal expansion from cells at diverse stages of differentiation. Gut 64, 1: 11 – 9 11 Barbieri I and Bannister AJ (2014) Evolution of cancer cell resistance versus intelligent design of epigenetic drugs. Drug Discovery Today: Disease Models DOI: 10.1016/j.ddmod [Kouzarides Group] 29 Gaggioli V, Zeiser E, Rivers D, Bradshaw CR, Ahringer J and Zegerman P (2014) CDK phosphorylation of SLD-2 is required for replication initiation and germline development in C. elegans. J Cell Biol 204, 6: 1075 12 Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P, Vries R, Peters PJ and Clevers H (2014) In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148, 1: 126 – 136 30 13 Bedzhov I, Graham SJ, Leung CY and Zernicka-Goetz M (2014) Developmental plasticity, cell fate specification and morphogenesis in the early mouse embryo. Philos Trans R Soc Lond B Biol Sci 369, 1657 DOI: 10.1098/rstb Gao P, Postiglione MP, Krieger TG, Hernandez L, Wang C, Han Z, Streicher C, Papusheva E, Insolera R, Chugh K, Kodish O, Huang K, Simons BD, Luo L, Hippenmeyer S and Shi SH (2014) Deterministic progenitor behavior and unitary production of neurons in the neocortex. Cell 159, 4: 775 – 788 31 14 Bedzhov I, Leung CY, Bialecka M and Zernicka-Goetz M (2014) In vitro culture of mouse blastocysts beyond the implantation stages. Nat Protoc 9, 12: 2732 – 2739 Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska E and Mansuy IM (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci 17, 5: 667 – 669 32 15 Bedzhov I and Zernicka-Goetz M (2014) Self-organizing properties of mouse pluripotent cells initiate morphogenesis upon implantation. Cell 156, 5: 1032 – 1044 Gardiol A and St Johnston D (2014) Staufen targets coracle mRNA to Drosophila neuromuscular junctions and regulates GluRIIA synaptic accumulation and bouton number. Dev Biol 392, 2: 153 – 167 33 Gold KS and Brand AH (2014) Optix defines a neuroepithelial compartment in the optic lobe of the Drosophila brain. Neural Dev 9: 18 16 Behjati S, Huch M, van Boxtel R, Karthaus W, Wedge DC, Tamuri AU, Martincorena I, Petljak M, Alexandrov LB, Gundem G, Tarpey PS, Roerink S, Blokker J, Maddison M, Mudie L, Robinson B, Nik-Zainal S, Campbell P, Goldman N, van de Wetering M, Cuppen E, Clevers H and Stratton MR (2014) Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513, 7518: 422 – 425 34 Gover O, Peretz Y, Mozes-Koch R, Maori E, Rabinowitch HD and Sela I (2014) Only minimal regions of tomato yellow leaf curl virus (TYLCV) are required for replication, expression and movement. Arch Virol 159, 9: 2263 – 2274 [Miska Group] 35 Grallert A, Boke E, Hagting A, Hodgson B, Connolly Y, Griffiths JR, Smith DL, Pines J and Hagan IM (2014) A PP1-PP2A phosphatase relay controls mitotic progression. Nature 517, 7532: 94 – 98 36 Graml V, Studera X, Lawson JL, Chessel A, Geymonat M, Bortfeld-Miller M, Walter T, Wagstaff L, Piddini E and Carazo-Salas RE (2014) A genomic multiprocess survey of machineries that control and link cell shape, microtubule organization, and cell-cycle progression. Dev Cell 31, 2: 227 – 239 37 Günesdogan U, Jäckle H and Herzig A (2014) Histone supply regulates S phase timing and cell cycle progression. Elife 3, e02443 [Surani Group] 38 Günesdogan U, Magnúsdóttir E and Surani MA (2014) Primoridal germ cell specification: a context-dependent cellular differentiation event. Philos Trans R Soc Lond B Biol Sci 369, 1657 4 Amaral PP and Bannister AJ (2014) Re-place your BETs: the dynamics of super enhancers. Mol Cell 56, 2: 187 – 189 [Kouzarides Group] 5 Amoyel M, Simons BD and Bach EA (2014) Neutral competition of stem cells is skewed by proliferative changes downstream of Hh and Hpo. EMBO J 33, 20: 2295 – 2313 6 Atkin J, Halova L, Ferguson J, Hitchin JR, Lichawska-Cieslar A, Jordan AM, Pines J, Wellbrock C and Petersen J (2014) Torin1-mediated TOR kinase inhibition reduces Wee1 levels and advances mitotic commitment in fission yeast and HeLa cells. J Cell Sci 127, Pt 6: 1346 – 1356 7 Aymard F, Bugler B, Schmidt CK, Guillou E, Caron P, Briois S, Iacovoni JS, Daburon V, Miller KM, Jackson SP and Legube G (2014) Transcriptionally active chromatin recruits homologous recombination at DNA doublestrand breaks. Nat Struct Mol Biol 21, 4: 366 – 374 Branching E11.5 mouse embryonic lung stained for ubiquitous lung marker, Nkx2.1 (yellow) & Hoechst (blue). (Christoph Budjan, Rawlins Group) 50 THE GURDON INSTITUTE 17 Belotserkovskaya R and Jackson SP (2014) Keeping 53BP1 out of focus in mitosis. Cell Res 24, 7: 781 – 782 18 Bergstralh DT and St Johnston D (2014) Spindle orientation: what if it goes wrong? Semin Cell Dev Biol 34, 140 – 145 19 Blasius M, Wagner SA, Choudhary C, Bartek J and Jackson SP (2014) A quantitative 14-3-3 interaction screen connects the nuclear exosome targeting complex to the DNA damage response. Genes Dev 28, 18: 1977 – 1982 20 Brownjohn PW and Ashton JC (2014) What can be concluded from blocking peptide controls? Appl Immunohistochem Mol Morphol 22, 8: 634 [Livesey Group] 21 Brownjohn PW, Reynolds JN, Matheson N, Fox J and Shemmell JB (2014) The effects of individualized theta burst stimulation on the excitability of the human motor system. Brain Stimul 7, 2: 260 – 268 [Livesey Group] Beta-tubulin staining for microtubules with DAPI counterstain, on cells which were cold-treated to induce microtubule depolymerisation and UV-treated to induce cell stress. (Laura Wagstaff, Piddini Group, in collaboration with Rafael Carazo-Salas.) 22 Centanin L, Ander JJ, Hoeckendorf B, Lust K, Kellner T, Kraemer I, Urbany C, Hasel E, Harris WA, Simons BD and Wittbrodt J (2014) Exclusive multipotency and preferential asymmetric divisions in post-embryonic neural stem cells of the fish retina. Development 141, 18: 3472 – 3482 23 Chen RA, Stempor P, Down TA, Zeiser E, Feuer SK and Ahringer J (2014) Extreme HOT regions are CpG-dense promoters in C. elegans and humans. Genome Res 24, 7: 1138 – 1146 24 Christophorou MA, Castelo-Branco G, Halley-Stott RP, Oliveira CS, Loos R, Radzisheuskaya A, Mowen KA, Bertone P, Silva JC, Zernicka-Goetz M, Nielsen ML, Gurdon JB and Kouzarides T (2014) Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature 507, 7490: 104 – 108 25 Di Cerbo V, Mohn F, Ryan DP, Montellier E, Kacem S, Tropberger P, Kallis E, Holzner M, Hoerner L, Feldmann A, Richter FM, Bannister AJ, Mittler G, Michaelis J, Khochbin S, Feil R, Schuebeler D, Owen-Hughes T, Daujat S and Schneider R (2014) Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription. Elife 3:e01632 [Kouzarides Group] THE GURDON INSTITUTE 51 INSTITUTE PUBLICATIONS INSTITUTE PUBLICATIONS 39 Hackett JA and Surani MA (2014) Regulatory principles of pluripotency: from the ground state up. Cell Stem Cell 15, 4: 416 – 430 60 Livesey FJ (2014) Human stem cell models of dementia. Hum Mol Genet 23, R1: R35 – R39 40 Halley-Stott RP, Jullien J, Pasque V and Gurdon J (2014) Mitosis gives a brief window of opportunity for a change in gene transcription. PLoS Biol 12, 7 61 41 Hara K, Nakagawa T, Enomoto H, Suzuki M, Yamamoto M, Simons BD and Yoshida S (2014) Mouse spermatogenic stem cells continually interconvert between equipotent singly isolated and syncytial states. Cell Stem Cell 14, 5: 658 – 672 Lowe N, Rees JS, Roote J, Ryder E, Armean IM, Johnson G, Drummond E, Spriggs H, Drummond J, Magbanua JP, Naylor H, Sanson B, Bastock R, Huelsmann S, Trovisco V, Landgraf M, Knowles-Barley S, Armstrong JD, White-Cooper H, Hansen C, Phillips RG, UK Drosophila Protein Trap Screening Consortium, Lilley KS, Russell S and St Johnston D (2014) Analysis of the expression patterns, subcellular localisations and interaction partners of Drosophila proteins using a pigP protein trap library. Development 141, 20: 3994 – 4005 42 43 Herzig B, Yakulov TA, Klinge K, Günesdogan U, Jäckle H and Herzig A (2014) Bällchen is required for self-renewal of germline stem cells in Drosophila melanogaster. Biol Open 3, 6: 510 – 521 [Surani Group] 62 Hindley CJ, Mastrogiovanni G and Huch M (2014) The plastic liver: differentiated cells, stem cells, every cell? J Clin Invest 124, 12: 5099 – 5102 44 Ho JW, Chen RA, Ahringer J et al. (2014) Comparative analysis of metazoan chromatin organization. Nature 512, 7515: 449 – 452 45 Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen MM, Ellis E, van Wenum M, Fuchs SA, de Ligt J, van de Wetering M, Sasaki N, Boers SJ, Kemperman H, de Jonge J, Ijzermans JN, Nieuwenhuis EE, Hoekstra R, Strom S, Vries RR, van der Laan LJ, Cuppen E and Clevers H (2014) Longterm culture of genome-stable bipotent stem cells from adult human liver. Cell 160, 1: 299 – 312 3D reconstruction of Drosophila adult posterior midgut. The oxygen-supplying trachea is shown in yellow and nuclei in of the gut epithelium in blue. (Saskia Suijkerbuijk, Piddini Group) 53 Koch B, Sanchez S, Schmidt CK, Swiersy A, Jackson SP and Schmidt OG (2014) Confinement and deformation of single cells and their nuclei inside size-adapted microtubes. Adv Healthc Mater 3, 11: 1753 – 1758 Korzelius J, Naumann SK, Loza-Coll MA, Chan JS, Dutta D, Oberheim J, Gläßer C, Southall TD, Brand AH, Jones DL and Edgar BA (2014) Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells. EMBO J 33, 24: 2967 – 2982 46 Irie N, Tang WW, and Surani MA (2014) Germ cell specification and pluripotency in mammals: a perspective from early embryogenesis. Reprod Med Biol 13, 4: 203 – 215 54 47 Ismail HM, Hurd PJ, Khalil MI, Kouzarides T, Bannister A and Gout I (2014) S6 kinase 2 is bound to chromatin-nuclear matrix cellular fractions and is able to phosphorylate histone H3 at threonine 45 in vitro and in vivo. J Cell Biochem 115, 6: 1048 – 1062 55 48 Izawa D and Pines J (2014) The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C. Nature doi: 10.1038/nature13911 Larrieu D, Britton S, Demir M, Rodriguez R and Jackson SP (2014) Chemical inhibition of NAT10 corrects defects of laminopathic cells. Science 344, 6183: 527 – 532 56 49 Jullien J, Miyamoto K, Pasque V, Allen GE, Bradshaw CR, Garrett NJ, Halley-Stott RP, Kimura H, Ohsumi K and Gurdon JB (2014) Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming. Mol Cell 55, 4: 524 – 536 Larrieu D, Rodriguez R and Britton S (2014) Chemical inhibition of NAT10 corrects defects of laminopathic cells. Médecine Sciences 30, 8-9: 745-747 [Jackson Group] 57 Lescroart F, Chabab S, Lin X, Rulands S, Paulissen C, Rodolosse A, Auer H, Achouri Y, Dubois C, Bondue A, Simons BD and Blanpain C (2014) Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development. Nat Cell Biol 16, 9: 829 – 840 58 Liang H, Esposito A, De S, Ber S, Collin P, Surana U and Venkitaraman AR (2014) Homeostatic control of polo-like kinase-1 engenders non-genetic heterogeneity in G2 checkpoint fidelity and timing. Nat Commun 5: 4048 [Pines Group] 59 Liu J, Spéder P and Brand AH (2014) Control of brain development and homeostasis by local and systemic insulin signalling. Diabetes Obes Metab 16 Suppl 1: 16 – 20 50 Keeling J, Bhaseen MJ and Simons BD (2014) Fermionic superradiance in a transversely pumped optical cavity. Phys Rev Lett 112, 14 51 Kim S, Günesdogan U, Zylicz JJ, Hackett JA, Cougot D, Bao S, Lee C, Dietmann S, Allen GE, Sengupta R and Surani MA (2014) PRMT5 protects genomic integrity during global DNA demethylation in primordial germ cells and preimplantation embryos Mol Cell 56, 4: 564 – 579 52 Knobel PA, Belotserkovskaya R, Galanty Y, Schmidt CK, Jackson SP and Stracker TH (2014) USP28 is recruited to sites of DNA damage by the tandem BRCT domains of 53BP1 but plays a minor role in double-strand break metabolism. Mol Cell Biol 34, 11: 2062 – 2074 52 THE GURDON INSTITUTE Loza-Coll MA, Southall TD, Sandall SL, Brand AH and Jones DL (2014) Regulation of Drosophila intestinal stem cell maintenance and differentiation by the transcription factor Escargot. EMBO J 33, 24: 2983 – 2996 63 Magnúsdóttir E and Surani MA (2014) How to make a primordial germ cell. Development 141, 2: 245 – 252 64 Malm AV, Harrison AW and Waigh TA (2014) Optical coherence tomography velocimetry of colloidal suspensions. Soft Matter 10, 41: 8210 – 8215 [Pines Group] 65 Marchalant Y, Brownjohn PW, Bonnet A, Kleffmann T and Ashton JC (2014) Validating antibodies to the cannabinoid CB2 receptor: antibody sensitivity is not evidence of antibody specificity. J Histochem Cytochem 62, 6: 395 – 404 [Livesey Group] 66 Matsusaka T, Enquist-Newman M, Morgan DO and Pines J (2014) Coactivator independent differences in how the metaphase and anaphase APC/C recognise the same substrate. Biol Open 3, 10: 904 – 912 67 Morais-de-Sá E, Mukherjee A, Lowe N and St Johnston D (2014) Slmb antagonises the aPKC/Par-6 complex to control oocyte and epithelial polarity. Development 141, 15: 2984 – 2992 68 Neville MC, Nojima T, Ashley E, Parker DJ, Walker J, Southall T, Van de Sande B, Marques AC, Fischer B, Brand AH, Russell S, Ritchie MG, Aerts S and Goodwin SF (2014) Male-specific fruitless isoforms target neurodevelopmental genes to specify a sexually dimorphic nervous system. Curr Biol 24, 3: 229 – 241 69 Nishi R, Wijnhoven P, le Sage C, Tjeertes J, Galanty Y, Forment JV, Clague MJ, Urbé S and Jackson SP (2014) Systematic characterization of deubiquitylating enzymes for roles in maintaining genome integrity. Nat Cell Biol 16, 10: 1016 – 18 70 Okayama S, Kopelovich L, Balmus G, Weiss RS, Herbert BS, Dannenberg AJ and Subbaramaiah K (2014) p53 protein regulates Hsp90 ATPase activity and thereby Wnt signaling by modulating Aha1 expression. J Biol Chem 289, 10: 6513 – 6525 [Jackson Group] 71 Olsson B, Legros L, Guilhot F, Strömberg K, Smith J, Livesey FJ, Wilson DH, Zetterberg H and Blennow K (2014) Imatinib treatment and Aβ42 in humans. Alzheimer’s and Dementia 10, 5: S374 – S380 72 Otsuki L, Cheetham SW and Brand AH (2014) Freedom of expression: Cell-type-specific gene profiling. Wiley Interdisciplinary Reviews: Developmental Biology 10.1002/wdev.149 73 Polato F, Callen E, Wong N, Faryabi R, Bunting S, Chen HT, Kozak M, Kruhlak MJ, Reczek CR, Lee WH, Ludwig T, Baer R, Feigenbaum L, Jackson S and Nussenzweig A (2014) CtIP-mediated resection is essential for viability and can operate independently of BRCA1. Journal of Experimental Medicine 211, 6: 1027-1036 74 Rawlins EL and Giangreco A (2014) The best laid schemes of airway repair. Eur Respir J 44, 2: 299 – 301 75 Ritsma L, Ellenbroek SI, Zomer A, Snippert HJ, de Sauvage FJ, Simons BD, Clevers H and van Rheenen J (2014) Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature 507, 7492: 362 – 365 76 Rodriguez-Bravo V, Maciejowski J, Corona J, Buch HK, Collin P, Kanemaki MT, Shah JV and Jallepalli PV (2014) Nuclear pores protect genome integrity by assembling a premitotic and Mad1-dependent anaphase inhibitor. Cell 156, 5: 1017 – 1031 [Pines Group] 77 Rosenthal N and Zernicka-Goetz M (2014) A tribute to Sir John Gurdon. Differentiation 88, 1: 1 – 2 Confocal image of human embryonic lung tissue (70 days old from date of conception), stained for Sox9 in green (marking the crucial multipotent progenitor population of the lung in the distal tip) and Sox2 in red (marking the proximal stalk) (Marko Nikolic, Rawlins Group) THE GURDON INSTITUTE 53 INSTITUTE PUBLICATIONS 78 Roshan A, Simons BD, Murai K and Jones PH (2014) Live imaging of human keratinocytes reveals two modes of cell proliferation. British Journal of Surgery 101: 5 – 5 79 Sarkies P and Miska EA (2014) Small RNAs break out: the molecular cell biology of mobile small RNAs. Nat Rev Mol Cell Biol 15, 8: 525 – 535 80 Savage KI, Gorski JJ, Barros EM, Irwin GW, Manti L, Powell AJ, Pellagatti A, Lukashchuk N, McCance DJ, McCluggage WG, Schettino G, Salto-Tellez M, Boultwood J, Richard DJ, McDade SS and Harkin DP (2014) Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability. Molecular Cell 54, 3: 445-459 [Jackson Group] 81 82 83 Schiavone D, Guilbaud G, Murat P, Papadopoulou C, Sarkies P, Prioleau MN, Balasubramanian S and Sale JE (2014) Determinants of G quadruplex-induced epigenetic instability in REV1-deficient cells. EMBO J 33, 21: 2507 – 2520 [Miska Group] Shulman JM, Imboywa S, Giagtzoglou N, Powers MP, Hu Y, Devenport D, Chipendo P, Chibnik LB, Diamond A, Perrimon N, Brown NH, De Jager PL and Feany MB (2014) Functional screening in Drosophila identifies Alzheimer’s disease susceptibility genes and implicates Tau-mediated mechanisms. Hum Mol Genet 23, 4: 870 – 877 Simmini S, Bialecka M, Huch M, Kester L, van de Wetering M, Sato T, Beck F, van Oudenaarden A, Clevers H and Deschamps J (2014) Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2. Nat Commun 5: 5728 84 Simon M, Sarkies P, Ikegami K, Doebley AL, Goldstein LD, Mitchell J, Sakaguchi A, Miska EA and Ahmed S (2014) Reduced insulin/IGF-1 signaling restores germ cell immortality to Caenorhabditis elegans Piwi mutants. Cell Rep 7, 3: 762 – 773 85 Singer ZS, Yong J, Tischler J, Hackett JA, Altinok A, Surani MA, Cai L and Elowitz MB (2014) Dynamic heterogeneity and DNA methylation in embryonic stem cells. Mol Cell 55, 2: 319 – 331 86 Southall TD, Davidson CM, Miller C, Carr A and Brand AH (2014) Dedifferentiation of neurons precedes tumor formation in Lola mutants. Dev Cell 28, 6: 685 – 696 87 Spéder P and Brand AH (2014) Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells. Dev Cell 30, 3: 309 – 321 88 Teperek M, Miyamoto K, Simeone A, Feret R, Deery MJ, Gurdon JB and Jullien J (2014) Sperm and spermatids contain different proteins and bind distinct egg factors. Int J Mol Sci 15, 9: 16719 – 16740 89 Tessarz P and Kouzarides T (2014) Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol 15, 11: 703 – 708 90 Tuysuz N, Koole W, Garcia TM, van Til N, Wagemaker G, Huch M, Vries RG and Clevers H (2014) Gene therapy of Type I mucopolysaccharidosis by liver organ stem cells in the mouse model. Human Gene Therapy 25, 11: A63 – A63 54 THE GURDON INSTITUTE TALKS BY INSTITUTE RESEARCHERS 91 Viré E, Curtis C, Davalos V, Git A, Robson S, Villanueva A, Vidal A, Barbieri I, Aparicio S, Esteller M, Caldas C and Kouzarides T (2014) The breast cancer oncogene EMSY represses transcription of antimetastatic microRNA miR-31. Mol Cell 53, 5: 806 – 818 92 Walsh I, Di Domenico T and Tosatto SC (2014) RUBI: rapid proteomicscale prediction of lysine ubiquitination and factors influencing predictor performance. Amino Acids 46, 4: 853 – 862 [Miska Group] 93 Walsh I, Giollo M, Di Domenico T, Ferrari C, Zimmermann O and Tosatto SC (2014) Comprehensive large-scale assessment of intrinsic protein disorder. Bioinformatics 31, 2: 201 – 208 [Miska Group] 94 Weick EM, Sarkies P, Silva N, Chen RA, Moss SM, Cording AC, Ahringer J, Martinez-Perez E and Miska EA (2014) PRDE-1 is a nuclear factor essential for the biogenesis of Ruby motif-dependent piRNAs in C. elegans. Genes Dev 28, 7: 783 – 796 95 Wickramasinghe VO, Andrews R, Ellis P, Langford C, Gurdon JB, Stewart M, Venkitaraman AR and Laskey RA (2014) Selective nuclear export of specific classes of mRNA from mammalian nuclei is promoted by GANP. Nucleic Acids Res 42, 8: 5059 – 5071 96 Wilson MT, Goodwin DP, Brownjohn PW, Shemmell J and Reynolds JN (2014) Numerical modelling of plasticity induced by transcranial magnetic stimulation. J Comput Neurosci 36, 3: 499 – 514 [Livesey Group] 97 Wolfram V, Southall TD, Günay C, Prinz AA, Brand AH and Baines RA (2014) The transcription factors islet and Lim3 combinatorially regulate ion channel gene expression. J Neurosci 34, 7: 2538 – 2543 98 Xi W, Schmidt CK, Sanchez S, Gracias DH, Carazo-Salas RE, Jackson SP and Schmidt OG (2014) Rolled-up functionalized nanomembranes as three-dimensional cavities for single cell studies. Nano Lett 14, 8: 4197 – 4204 99 Xu H, Xian J, Vire E, McKinney S, Wei V, Wong J, Tong R, Kouzarides T, Caldas C, Aparicio S (2014) Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells. J Pathol 234, 3: 386 – 397 100 Yakulov T, Günesdogan U, Jäckle H and Herzig A (2014) Bällchen participates in proliferation control and prevents the differentiation of Drosophila melanogaster neuronal stem cells. Biol Open 3, 10: 881 – 886 101 Yata K, Bleuyard J-Y, Nakato R, Ralf C, Katou Y, Schwab R, Niedzwiedz W, Shirahige K and Esashi F (2014) BRCA2 coordinates the activities of cellcycle kinases to promote genome stability. Cell Reports 7, 5: 1547 – 1559 [Pines Group] 102 Zernicka-Goetz M and Hadjantonakis AK (2014) From pluripotency to differentiation: laying foundations for the body pattern in the mouse embryo. Philos Trans R Soc Lond B Biol Sci 369, 1657 JANUARY JOHN GURDON: Medical Faculty: Annal Medical Fellows/Students, Cambridge, UK TONY KOUZARIDES: HHMI/NYU Langone Medical Center, New York, New York, USA ERIC MISKA: Genome Dynamics Seminar Series, Montpelier, France ERIC MISKA: Barbados micRNA Anniversary Meeting, Bridgetown, Barbados BEN SIMONS: Curie Institute, Paris, France AZIM SURANI: Insitute for Stem Cell Biology and Regenerative Medicine, Bangalore, India PHILIP ZEGERMAN: University of Nottingham, UK FEBRUARY ANDREA BRAND: LS2 (Life Sciences Switzerland) Annual Meeting, Lausanne, Switzerland ANDREA BRAND: Developmental Biology Society Meeting, Paris, France ANDREA BRAND: 7th Asian Pacific Organization for Cell Biology Congress, Singapore JOHN GURDON: Bangalore Bio: biotech for a better tomorrow, Bangalore, India JOHN GURDON: Indian Institute of Science, Bangalore, India JOHN GURDON: Old Etonian Association, London, UK JOHN GURDON: Cambridge Enterprise and Technology Club, Cambridge, UK JOHN GURDON: Kings College, London, UK MERITXELL HUCH: 3Rs Prize Lecture, London, UK MERITXELL HUCH: 3-D Cell Cultures & Drug Discovery, Vienna, Austria MERITXELL HUCH: Webminar ISSCR, Skokie, Illinois, USA TONY KOUZARIDES: Michael Lund Nielsen, University of Copenhagen, Denmark TONY KOUZARIDES: Institute Pasteur, Paris, France ERIC MISKA: BIG, Norwegian Biochemical Society, Oslo, Norway ERIC MISKA: RNAi 2014, Oxford, UK ERIC MISKA: Annual Lausanne Genomic Days, Lausanne, France JON PINES: 2nd UK-Korea Mitosis Workshop, Seoul, South Korea MARCH JULIE AHRINGER: Keystone Chromatin Meeting, Oberstdorf, Germany ANDREA BRAND: 15th Servier-IGIS Symposium Neural Orchestration of Metabolism and Islet Function, St Jean Cap Ferrat, France NICK BROWN: Plenary speaker, International Meeting of the German Society for Cell Biology, Regensburg, Germany JOHN GURDON: College de France, Paris, France JOHN GURDON: Bishops Stortford College, UK JOHN GURDON: Society of Toxicology, Phoenix, Arizona, USA MERITXELL HUCH: ILTS Workshop, Rotterdam, Netherlands STEVE JACKSON: Abcam Meeting, St. Kitts, Saint Kitts And Nevis STEVE JACKSON: BSCB/BSDB Annual Spring Meeting, Coventry, UK STEVE JACKSON: Cancer Science Symposium, Cambridge, UK TONY KOUZARIDES: Keystone Symposia, Oberstdorf, Germany ERIC MISKA: Tel Aviv Universit, Tel Aviv, Israel EUGENIA PIDDINI: BSCB/BSDB Annual Spring Meeting, Coventry, UK EMMA RAWLINS: BSCB/BSDB Annual Spring Meeting, Coventry, UK DANIEL ST JOHNSTON: BSCB/BSDB Annual Spring Meeting, Coventry, UK AZIM SURANI: Keystone Symposia: Chromatin mechanisms and cell physiology, Oberstdorf, Germany PHILLIP ZEGERMAN: St. Olaves Grammar School, Orpington, UK PHILLIP ZEGERMAN: University of Dundee, Dundee, UK APRIL JULIE AHRINGER: Wellcome Trust Conference Chromatin: From nucleosomes to chromosomes, Hinxton, UK ANDREA BRAND: College de France, Paris, France NICK BROWN: Seminar, Dept of Pharmacology, Yale School of Medicine, New Haven, Connecticut, USA NICK BROWN: Seminar, Department of Cell and Systems Biology, Toronto, Canada JOHN GURDON: Keystone Symposium, Squaw Creek, California, USA JOHN GURDON: Penn’s Institute for Regenerative Medicine, Pennsylvania, USA JOHN GURDON: John Ray Society, Cambridge, UK STEVEN MOORE: The future of research and clinical applications in neuroscience, Genoa, Italy JON PINES: Ramon Areces Foundation, Santander, Spain JON PINES: Brunel University, Brunel, UK JON PINES: Newcastle University, Newcastle, UK JON PINES: DKFZ-ZMBH Alliance Meeting, Heidelberg, Germany EMMA RAWLINS: ERS Research Seminar ‘The many faces of stem cells in respiratory diseases’, Barcelona, Spain EMMA RAWLINS: International Society for Cellular Therapy Meeting: Satellite session on tracheal engineering, Paris, France AZIM SURANI: DKFZ-ZMBH, Heidelberg, Germany EMMANUELLE VIRE: Institute Cochin, Paris, France MAY JULIE AHRINGER: Keynote Speaker: European C elegans Meeting, Berlin, Germany JULIE AHRINGER: University of Edinburgh, UK THE GURDON INSTITUTE 55 TALKS BY INSTITUTE RESEARCHERS TALKS BY INSTITUTE RESEARCHERS ANDREA BRAND: European Molecular Biology Laboratory (EMBL), Heidelberg, Germany ANDREA BRAND: The Stem Cell Niche - Development and Disease Conference, Copenhagen, Denmark NICK BROWN: UK Drosophila Developmental Cell Biology Workshop 2014, Edzell, UK JOHN GURDON: Hay Festival, Hay-on Wye, UK JOHN GURDON: School of Biological Sciences Postdoc Retreat, Cambridge, UK MERITXELL HUCH: Pint of Science Festival, Cambridge, UK MERITXELL HUCH: Stem Cell Research mini conference, Imperial College, London, UK STEVE JACKSON: Abcam Meeting Mechanisms of Recombinations: 50th Anniversary Meeting of the Holliday Model, Alicante, Spain BENJAMIN KLAPHOLZ: 5th French Cell Adhesion Club Symposium, Marseille, France ERIC MISKA: Translational Control of Brain Function & Epigenomic Engineering, London, UK ERIC MISKA: Wellcome Trust Translation conference, London, UK ERIC MISKA: MPI Tuebingen, Germany JON PINES: Dundee University, UK BEN SIMONS: The Stem Cell Niche - Development and Disease, Copenhagen, Denmark DANIEL ST JOHNSTON: ESF/EMBO Conference on Cell Polarity and Membrane Trafficking, Pultusk, Poland AZIM SURANI: Reprogramming during development, induced pluripotency and disease, Paris, France JUNE ANDREA BRAND: Lawrence Berkeley National Laboratory, Berkeley, California, USA ANDREA BRAND: EMBO International Workshop on Molecular and Developmental Biology of Drosophila, Crete, Greece NICK BROWN: EMBO International Workshop on Molecular and Developmental Biology of Drosophila, Crete, Greece NICK BROWN: Seminar, Biomedical Research Foundation, Athens, Greece JOHN GURDON: Rockefeller Symposium + Honorary degree, New York, UK MERITXELL HUCH: BASL - British Association for the Study of the Liver, Seal Hayne, Devon, UK ERIC MISKA: ETH Zurich Seminar, Switzerland EUGENIA PIDDINI: EMBO, Crete, Greece BEN SIMONS: Theory of Living Matter Group, Cambridge, UK AZIM SURANI: ISSCR Annual Meeting, Vancouver, Canada 56 THE GURDON INSTITUTE JULY JULIE AHRINGER: University of Washington, Seattle, USA JOHN GURDON: Chromatin Club/Abcam, London, UK JOHN GURDON: University of Cambridge, Cambridge, UK MERITXELL HUCH: FASEB liver meeting, Keystone, Colorado, USA STEVE JACKSON: Association of Radiation Research Meeting, Sussex, UK ERIC MISKA: RNA Habitats, Salzburg, Austria STEVEN MOORE: 2nd Stem BANCC workshop on human cerebral cortex differentiation, Cambridge, UK BEN SIMONS: Theory of Living Matter Group, Cambridge, UK JAMES SMITH: 2nd Stem BANCC workshop on human cerebral cortex differentiation, Cambridge, UK DANIEL ST JOHNSTON: Wellcome Fellows Meeting, London, UK AZIM SURANI: Cell Symposia: Transcriptional regulation in development, Chicago, Illinois, USA AUGUST ANDREA BRAND: Santa Cruz Developmental Biology Meeting, California, USA YARON GALANTY: Benzon Symposium No.60 Nuclear Regulation by Ubiquitin, Copenhagen, Denmark JENNY GALLOP: Xenopus Meeting, California, USA JOHN GURDON: 15th Xenopus Meeting, Asiloma, California, USA TONY KOUZARIDES: EMBL, Heidelberg, Germany JON PINES: 60th Benzon Symposium, Copenhagen, Denmark AZIM SURANI: Gordon Conference, Mammalian reproduction, translating basic science into clinical applications, New London, New Hampshire, USA EVA-MARIA WEICK: CSHL Conference - Regulatory & non-coding RNAs, Long Island, New York, USA PHILIP ZEGERMAN: Xenopus Meeting, Pacific Grove, California, UK SEPTEMBER JULIE AHRINGER: Chromatin and Epigenetics Conference, Cold Spring Harbor, USA PAULO AMARAL: Uppsala University, Uppsala, Sweden PAULO AMARAL: Stockholm RNA society, Stockholm, Sweden NICK BROWN: Get Connected 4: Cellular microenvironment, Manchester, UK NICK BROWN: Shaping Cells and Organisms Symposium, Cologne, Germany TATYANA DIAS: ARUK Cambridge Network Committee, Cambridge, UK JENNY GALLOP: EMBO Advanced Course, Heidelberg, Germany JOHN GURDON: 1st Congress of the Polish Biochemistry, Cell Biology, Biology, Biophysics & Bioinformatics, BIO 2014, Warsaw, Poland JOHN GURDON: Victor Chang Cardiac Research Institute and Garvan Institute of Medical Research, Sydney, Australia JOHN GURDON: Combio 2014, Canberra, Australia JOHN GURDON: Monash University, Melbourne, Australia MERITXELL HUCH: The European Cancer Stem Cell Research Institute Symposium, Cardiff, UK STEVE JACKSON: Cancer Pharmacogenomics and Targeted Therapies Conference, Hinxton, UK PETER KIRWAN: From Cells to Tissue: Stem Cells, Tissue Repair and Tissue Engineering for Diabetes, Eye Disease and Neurodengerative Diseases, Dublin, Republic of Ireland TONY KOUZARIDES: Cold Spring Harbor Laboratory (CHSL), Cold Spring Harbor, New York, USA ERIC MISKA: Fondazione Cariplo, Brescia, Italy EUGENIA PIDDINI: JEDI Meeting, Marseille, France DANIEL ST JOHNSTON: Cologne’s International Graduate Programme in Biology and Maria Leptin’s 60th Birthday, Institute for Genetics, Cologne, Germany BEN SIMONS: Japan Neuroscience Society, Yokohama, Japan BEN SIMONS: Centre for Development Biology, Kobe, Japan BEN SIMONS: National Institute of Basic Biology, Okazaki, Japan JULIE WATSON: European Respiratory Society, Munich, Germany OCTOBER JULIE AHRINGER: EMBO Conference, Cargese, Corsica, France ALPER AKAY: Herchel Smith Symposiusm, Cassis, France ANDREW BANNISTER: UCL, London, UK ANDREA BRAND: Neurofly 2014, Hersonissos, Crete, Greece ANDREA BRAND: Developmental Biology Course, Insitut Curie, Paris, France JOHN GURDON: Abcam, Chromatin & Epigenetics: from Omics to Stem Cells, Strasbourg, France JOHN GURDON: Harveian Oration, London, UK JOHN GURDON: Stem Cells meeting, Provence, France MERITXELL HUCH: Next generation cell culture models workshop, Hinxton, UK TONY KOUZARIDES: BDEBATE PEBC-IDIBELL, Barcelona, Spain TONY KOUZARIDES: Abcam, Strasbourg, France TONY KOUZARIDES: Wellcome Trust, Hinxton, Cambridge, UK ERIC MISKA: MPI Seminar, Cologne, Germany ERIC MISKA: IMB Conference: Nuclear RNA in Gene Regulating & Chromatin Structure, Mainz, Germany ERIC MISKA: Living Matter Talk at Rockefeller University, New York City, New York, USA EUGENIA PIDDINI: EMBO, Stockholm, Sweden JON PINES: CR UK Clare Hall Laboratories, London, UK AZIM SURANI: Foundation Les Treilles Meeting, Nice, France AZIM SURANI: State Key Laboratory of Reproductive Biology (SKLRB), Beijing, China MÉLANIE TANGUY: Herchel Smith Symposiusm, Cassis, France NOVEMBER ALPER AKAY: Churchill College, Cambridge, UK YARON GALANTY: IRIBHM, Brussels, Belgium JOHN GURDON: ISD and BSDB, London, UK JOHN GURDON: Wellcome Trust Researcher Meeting: Development, Ageing and Regenerative Medicine, Ware, UK MERITXELL HUCH: Erasmus Liver Day, Rotterdam, Netherlands MERITXELL HUCH: British Society for Developmental Biology, London, UK STEVE JACKSON: Molecular mechanisms of cellular surveillance and damage responses, Heidelberg, Germany TONY KOUZARIDES: University of Miami, Miller School of Medicine, Miami, Florida, USA ERIC MISKA: MCB Seminar, Boston, Massachusetts, USA ERIC MISKA: MRC Leicester Unit Seminar Series, Leicester, UK JON PINES: Southampton University, Southampton, UK JON PINES: EPFL, Lausanne, Switzerland EMMA RAWLINS: National Institute for Medical Research, London, UK DANIEL ST JOHNSTON: Distinguished Lecture Max Planck, Martinsried, Germany BEN SIMONS: Wellcome Trust Researcher Meeting on Pathogens, Immunity and Cell Biology , Hertfordshire, UK AZIM SURANI: International Society for Stem Cells (ISSCR): Global controls in Stem Cells, Singapore, Singapore AZIM SURANI: Wellcome Trust Researcher Meeting, Ware, UK PHILIP ZEGERMAN: 3Rs Meeting, Tokyo, Japan DECEMBER ANDREA BRAND: UK/Japan Workshop University College London, UK JENNY GALLOP: University of Kent, Canterbury, UK JOHN GURDON: MRC, London, UK JOHN GURDON: CSAR Churchill College, Cambridge, UK TONY KOUZARIDES: Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany TONY KOUZARIDES: RIKEN and UCL, London, UK ERIC MISKA: Translational Science Update, London, UK ERIC MISKA: MPI Epigenetics Meeting, Freiburg, Germany DMITRY NASHCHEKIN: Sainsbury Laboratory, Research in Genetics Day, Cambridge, UK EMMA RAWLINS: DanStem, Copenhagen, Denmark THE GURDON INSTITUTE 57 GURDON INSTITUTE SEMINARS / STAFF AFFILIATIONS LENT TERM 1) 21 January, Cédric Blanpain, Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles, Belgium: “Stem cell dynamics during development, homeostasis and cancer” 2) 28 January, ( The Anne McLaren Lecture) Maria Leptin, EMBO, Heidelberg, Germany: “Cell shape and morphogenesis: sub cellular and supra-cellular mechanisms” 3) 11 February, Pierre Gönczy, EPFL, Lausanne, Switzerland: “Mechanisms of centriole assembly” 4) 11 March, Detlef Weigel, Max Planck Institute for Developmental Biology, Tübingen, Germany: “Origins and consequences of (epi)genetic variation in Arabidopsis thaliana and its relatives” 5) 25 March, Claude Desplan, Department of Biology, New York University, USA: “Generating neuronal diversity: stochastic or deterministic choices” MICHAELMAS TERM 6) 14 October, Alexander Aulehla, European Molecular Biology, Laboratory (EMBL), Heidelberg, Germany: “Self-organization of genetic oscillators during mouse mesoderm development” 7) 21 October, Péter Lénárt, European Molecular Biology, Laboratory (EMBL), Heidelberg, Germany: “Microtubules need actin’s help in large oocytes, to collect chromosomes and to break the nuclear envelope” 8) 25 November, W. James Nelson, Department of Biology, Stanford University, USA: “Evolution of cell-cell adhesion, and new insights into mechanisms in animals ” 9) 2 December, Iain Hagan, Cancer Research UK, Manchester Institute, University of Manchester: “A Protein phosphatase 1/protein phosphatase 2A relay controls mitotic progression” 58 THE GURDON INSTITUTE OTHER INFORMATION STAFF AFFILIATIONS JULIE AHRINGER is a member of the Scientific Advisory Boards of the MRC Clinical Sciences Centre and Wormbase. ANDREA BRAND is a member of Council of The Royal Society, member of the Wellcome Trust/Royal Society Sir Henry Dale Fellowship Committee and a Founding Board Member of The Rosalind Franklin Society (USA). She is on the Board of Directors of the Cambridge Science Centre and is a Patron of the Cambridge Science Festival. JOHN GURDON is an honorary member of the British and American Anatomical Societies, a board member of Diagnostics for the Real World and a member of the Faculty of 1,000. STEVE JACKSON is an Associate Faculty Member of the Wellcome Trust Sanger Institute and is founding Scientist and Chief Scientific Officer of MISSION Therapeutics Ltd. He is a member of the Scientific Advisory Boards for the MRC Protein Phosphorylation and Ubiquitylation Unit (Dundee), the Beatson Institute (Glasgow), the MRC Toxicology Unit (Leicester), the Radiation Oncology and Biology Institute (Oxford), the MRC Clinical Sciences Centre (London) and the Netherlands Cancer Institute (Amsterdam). He is on the Steering Committee for the Cambridge Cancer Centre, and is a member of the CRUK Science Committee. MAGDALENA ZERNICKA-GOETZ is a Fellow of The Academy of Medical Sciences and EMBO HONOURS AND AWARDS JULIE AHRINGER – Professorship, University of Cambridge ANDREA BRAND – Honorary Fellow, Brasenose College, University of Oxford. NICK BROWN – Professorship, University of Cambridge JOHN GURDON – Honorary Degree, Rockefeller University MERITXELL HUCH – Wellcome-Beit Prize, NC3Rs International Prize STEVE JACKSON – Fellowship of Imperial College Faculty of Medicine STEVE JACKSON AND DELPHINE LARRIEU – Winners of GSK Discovery Fast Track Challenge BEN SIMONS – Institute of Physics Rosalind Franklin Medal PHILIP ZEGERMAN – EMBO Young Investigator AZIM SURANI – Jawaharlal Nehru Science Fellowship (JNSF), ISSCR McEwen Award for Innovation AZIM SURANI – Cell; Nature Communications; Cell Stem Cell; BMC Epigenetics and Chromatin; Epigenome; Epigenomics; Epigenetic Regulators; Regenerative Medicine; Differentiation; Stem Cell Research and Therapy; Faculty of 1,000; Cell Research; Cell Discovery MAGDALENA ZERNICKA-GOETZ – Development; Differentation; Developmental Dynamics; Cells INTERNATIONAL SCIENTIFIC ADVISORY BOARD DR GENEVIEVE ALMOUZNI, Institut Curie, Paris, France DR ADRIAN BIRD, Wellcome Trust Centre for Cell Biology, University of Edinburgh DR STEVE COHEN, Institute of Molecular and Cell Biology, Singapore DR JUDITH KIMBLE, Department of Biochemistry, University of Wisconsin-Madison, USA DR ELISABETH KNUST, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany DR ROBB KRUMLAUF (Chairman), Stowers Institute for Medical Research, Kansas City, USA TONY KOUZARIDES is a member of the Cancer Research UK Science and Strategy Advisory Group, part of the Scientific Advisory Board for the Centre for Genomic Research (Spain), the Institute of Molecular Biology (Crete) and the Centre for Epigenetics and Biology (Spain). He is the founder and director of a Spanish cancer charity Vencer el Cancer (Conquer Cancer) and a founder of Chroma Therapeutics and Abcam Plc. THE GURDON INSTITUTE – Athena SWAN Bronze Award DR MATTHIAS PETER, ETH Zurich EDITORIAL BOARDS OF JOURNALS CHAIRMAN OF THE MANAGEMENT COMMITTEE JULIE AHRINGER – eLife; PLoS Biology; PLoS Genetics; Molecular Systems Biology ERIC MISKA is an Honorary Faculty Member of the Wellcome Trust Sanger Institute ANDREA BRAND – eLife; Neural Development; Fly; Biology Image Library PROFESSOR DUNCAN MASKELL, Head of the School of the Biological Sciences and Marks & Spencer Professor of Farm Animal Health, Food Science & Food Safety, Department of Veterinary Medicine JONATHON PINES is a member of the Scientific Advisory Board for the UMR144, Institut Curie, Paris, France, and the Evaluation Panel of the Institute of Biochemistry, ETH, Zurich. DANIEL ST JOHNSTON is a Director of the Wellcome Trust Four-Year PhD programme in Developmental Biology at the University of Cambridge, a non-executive Director of the Company of Biologists, and acting Editor of Disease Models and Mechanisms. AZIM SURANI is a member of the Steering Committee of the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, and theme leader of the Pluripotency Programme. He is also a member of the Cambridge-India Partnership Advisory Group, founder and Chief Scientific Advisor for CellCentric Ltd, a member of the Steering Committee for the UK Stem Cell Bank, and a member of the Royal Society Hooke Committee. He is also a member of the Scientific Advisory Board of the Institute of Stem Cell Biology and Regenerative Medicine, Bangalore, India. JOHN GURDON – Current Biology; Development; Faculty of 1,000; Growth and Differentiation; International Journal of Developmental Biology; Proceedings of the National Academy of Sciences of the USA MERITXELL HUCH – Cogent Biology STEVE JACKSON – Aging; Biomolecules; Carcinogenesis; DNA Repair ; EMBO Journal ; Genes and Development; The Scientist; Science Signaling (Board of Reviewing Editors) RICK LIVESEY – BMC Developmental Biology; Molecular Autism EMMA RAWLINS – Pediatric Research JON PINES – EMBO Journal; EMBO Reports; Open Biology; eLife BEN SIMONS – Development DANIEL ST JOHNSTON – Development; Faculty of 1,000 THE GURDON INSTITUTE 59 DESTINATIONS OF LEAVERS DURING 2014 GROUP LEADERS MAGDALENA ZERNICKA-GOETZ: Group Leader, Department of Physiology, Development & Neuroscience, University of Cambridge POSTDOCTORAL RESEARCHERS HOZEFA AMIJEE: Project Manager, Total Scientific, Cambridge, UK (Livesey Lab) FRANCESCO ANTONICA: Postdoctoral Researcher, Department of Physiology, Development & Neuroscience, University of Cambridge (ZernickaGoetz Lab) ALYSON ASHE: Group Leader, University of Sydney, Australia (Leaver 2013) IVAN BEDZHOV: Postdoctoral Researcher, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) MONIKA BIALECKA: Postdoctoral Researcher, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) MIKE CHESNEY: Senior Scientist, Illumina, Cambridge UK (Ahringer Lab) MARIA CHRISTOPHOROU: Group Leader, MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, UK (Kouzarides Lab) PHILIPPE COLLIN: Senior Scientist, Horizon Discovery, Waterbeach, Cambridgeshire UK (Pines Lab) SVEN HUELSMANN: Lecturer and Study Coordinator at the University of Tübingen (Brown Lab) AGNIESZKA JEDRUSIK: Postdoctoral Researcher, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) OLEG KOVALEVSKIY: Career Development Fellow, MRC-LMB, Cambridge, UK (Zegerman Lab) TAKAHIRO MATSUSAKA: Senior Scientist, Horizon Discovery, Waterbeach, Cambridgeshire UK (Pines Lab) GAELLE RECHER: Postdoctoral Researcher, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) JOSANA RODRIGUEZ: Group Leader, Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, UK (Ahringer Lab) PETER SARKIES: Group Leader, Epigenetics Division at the MRC Clinical Sciences Centre, Imperial College, London (Miska Lab) MARTA SHAHBAZI ALONSO: Postdoctoral Researcher, Department of Physiology, Development & Neuroscience, University of Cambridge (ZernickaGoetz Lab) TONY SOUTHALL: Lecturer, Department of Life Sciences, Imperial College, London, UK (Brand Lab) PETER TESSARZ: Group Leader, Max Planck Institute for Biology of Ageing, Cologne (Kouzarides Lab) JON TRAVERS: Postdoctoral Fellow, Medimmune, Cambridge, UK (Jackson Lab) EMMANUELLE VIRÉ: Senior Investigator, MRC Prion Unit, London UK (Kouzarides Lab) ASTRID WALRANT: Maitre de Conferences (Lecturer), Universite Pierre et Marie Curie (UPMC), Chemistry Faculty, Paris, France (Gallop Lab) 60 THE GURDON INSTITUTE RESEARCH ASSISTANTS/TECHNICIANS AMY CORDING: Research Assistant, Department of Biology, University of York, UK (Miska Lab) ANDY COX: Research Assistant, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) DJEM KISSIOV: PhD Student, University of California, Berkeley, USA (Ahringer Lab) AMELIA McGLADE: Research Assistant, Garvan Institute, Sydney (Livesey Lab) CHANDRIKA RAO: PhD Student, University of Edinburgh, UK (Rawlins Lab) Research PhD/MPhil STUDENTS DARYA AUSIANNIKAVA: Postdoctoral Associate, Dr Thorsten Allers’ lab, University of Nottingham, UK (Ahringer Lab) JESSICA BROWN: SpR Medical Oncology, Addenbrooke’s Hospital NHS Trust, Cambridge UK (Jackson Lab) LEAH BURY: PhD, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) ESTEBAN CONTRERAS SEPULVEDA: Postdoctoral Researcher, University of Chile, Santiago, Chile (Brand Lab) KATRINA GOLD: Postdoctoral Researcher, UCSF, San Francisco, USA (Brand Lab) MOHAMMED GOOLAM: PhD Student, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) SARAH GRAHAM: PhD Student, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) ANNABEL GRIFFITHS: Travelling, Volunteer in Cambodia, Science Consultant on return to UK (Brown Lab) TIMM HAACK: Postdoctoral Researcher, Salim Seyfried’s Lab, Hannover Medical School, Germany (St Johnston Lab) RICHARD HALLEY-STOTT: Medical Degree, University of Cape Town, South Africa (Gurdon Lab) MORITZ HERRMANN: Pharmaceuticals Analyst, GlobalData, London (Ahringer Lab) PETER KIRWAN: Senior Postdoctoral Scientist, Talisman Therapeutics, Cambridge UK (Livesey Lab) CHUEN YAN LEUNG: PhD Student, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) AGATA LICHAWSKA: Postdoctoral position, Krakow, Poland (Pines Lab) KENNETH MURFITT: Senior Scientist, Novartis, Maidstone, Kent (Miska Lab) MARYNA PANAMAROVA: PhD Student, Department of Physiology, Development & Neuroscience, University of Cambridge (Zernicka-Goetz Lab) MARTA TEPEREK-TKACZ: Business Development Consultant, Oxbridge Biotech Roundtable, London, UK (Gurdon Lab) STAN WANG: Completing PhD in USA before returning to Medical School in Columbia (Gurdon Lab) BEATA WYSPIANSKA: Senior Scientist, GSK, Stevenage, UK (Kouzarides Lab) The Institute on retreat, October 2014 (photo by James Smith, Livesey Group) ACKNOWLEDGEMENTS Prospectus produced in the Wellcome Trust/Cancer Research UK Gurdon Institute. Edited by Ann Cartwright, production by Alastair Downie Group photographs by James Smith, Livesey Group. Print management by H2 Associates, Cambridge Front cover: False-coloured DIC images of HeLa cells at different stages of mitosis, surrounding the central image of the double gene knockout celebration cake. The cake itself is also a ‘double knockout’ of sources of allergens; gluten and almond. Time lapse images captured on Deltavision microscope (Keiko Yata and Oxana Nashchekina, Pines Group) Back cover: The Institute tea party, in recognition of one million kWh saved since launching our energy saving campaign in March 2012 (photo by Paul Holland, Office of External Affairs and Communications, University of Cambridge) Wellcome Trust/Cancer Research UK Gurdon Institute The Henry Wellcome Building of Cancer and Developmental Biology University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, United Kingdom Telephone: +44 (0)1223 334088 Fax: +44 (0)1223 334089 http://www.gurdon.cam.ac.uk e-mail: info@gurdon.cam.ac.uk