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2013 Contents 2013 Contents The Institute ……………………………………………2 2013 Progress Report ………………..…………....4 Research Groups Roger Barker Parkinson’s and Huntington’s disease……….8 Kevin Chalut The Physical Biology of Pluripotency and Differentiation..…………………………………….…10 Robin Franklin Adult Neural Stem Cells and CNS Regeneration…………………………………….…....12 Michaela Frye Epithelial Stem Cell Homeostasis and Cancer………………………………………………………14 Bertie Gottgens Transcriptional Regulation of Normal and Leukaemic Blood Stem Cells..……………….….16 Tony Green Haematopoiesis………………………………….…...18 Brian Hendrich Transcriptional Control of Stem Cell Fate….20 Brian Huntly Leukaemia Stem Cell Biology …………...….…22 Kim Jensen Epithelial Development, Maintenance and Regeneration……………………….………………….24 Thora Karadottir Neurotransmitter Signalling to CNS Progenitor Cells……………………………...……….26 Bon-Kyoung Koo Homeostatic Regulation of Adult Stem Cells…………………………………………………………28 Vision: “Deep understanding of stem cell biology for prevention and treatment of human disease.” Mark Kotter Juan-Jose Ventura Neural Stem Cells, Cellular Reprogramming and Bronchioalveolar cellular and molecular hierarchy in Regenerative Medicine……….…….……………………………...30 homeostasis and disease ………...………………....……..54 Rick Livesey Alan Warren Human stem cell models of dementia…….…………….…..32 Stem cell subversion and bone marrow failure syndromes……………………………………………………...…..56 Jennifer Nichols Embryonic Pluripotency…………………………………………….34 Anton Wutz Epigenetic Regulation and Cell Identity Control......58 Katrin Ottersbach The Developmental Origins of Blood Stem Cells……….36 Roger Pedersen Mechanics of Mesoderm Differentiation in Mammalian The Institute Pluripotent Stem Cells…………………………………….………..38 Stefano Pluchino Facilities Central Nervous System Repair….……………………………..40 Bioinformatics…………………………………………….……….60 Flow Cytometry…………………………………………………...61 Emma Rawlins Histology………………………………………………………….....62 Stem Cell Fate in the Mammalian Lung …………………….42 Imaging………………………………………………………………..63 Next Generation Sequencing Libraries …………………64 Jose Silva Tissue Culture……………………………………………………...65 Biology of Induced Pluripotency …………………….………...44 IT.………………………………………………………………………...66 Other Resources…………………………………………………..67 Ben Simons Tracing stem cell fate in development, maintenance, and disease ………………………………...……………………………46 Affiliate Members………………………………………………..68 Committees ………….…………………………………………..70 Austin Smith Funding ……………………...………………………...…………..72 Stem Cell Potency………………………..……..…………...……….48 Highlights of 2013………………………………………………..74 2013 SCI International Symposium………………...…...76 Azim Surani Seminars and Public Engagement Events.……..…….78 Specification and programming of the germline for PhD Programme in Stem Cell Biology & totipotency and development.………………………………....50 Medicine………………………………………...…………………..80 Alumni………………………………………………………………...82 Ludovic Vallier Career Progression - Students………………………..…...83 Mechanisms Controlling Differentiation of Pluripotent 2013 Publications ………………………………………..……..84 Stem Cells into Definitive Endoderm………………………...52 Appendix 1 - Additional Group Information.………..92 Strategy: Fundamental science of the highest quality and rigour to elucidate the governing principles of stem cell identity and behaviour. Translational research taking basic science into the clinic to investigate stem cell malfunction in disease, and to define the role of stem cells in regenerative medicine. Training and mentoring of talented researchers including clinician scientists to implement, spread and evolve the vision. Collaboration with academia, clinicians and industry in the UK and worldwide to accelerate and enhance understanding of stem cells and their applications. Communication and public engagement providing reliable information, useful resources, and dialogue opportunities for a range of audiences including schools, policy makers, patient Austin Smith groups, professional bodies, and the media. Institute Director The Institute Research Themes Stem Cell Research Pluripotency Stem cell science is providing a stream of new knowledge about how our Pluripotent stem cells can be derived bodies are made and maintained. This from early embryos, produced by research brings the promise that better epigenetic conversion of germ cells, understanding of stem cells will lead to or created by transcription factor future medical applications. Treatments mediated reprogramming of somatic may come through several routes: cells. Our fundamental investigations are directed at the molecular Human stem cells grown in the foundations of pluripotency, laboratory can be used to produce mechanisms of lineage-specific experimental models of diseased differentiation and comparative tissues and to test therapeutic drugs. analyses between rodent and human. Some diseases, including forms of cancer, involve abnormal behaviour Theme Leader: Surani of stem cells. As we learn how to Principal Investigators: Hendrich, Nichols, Silva, Smith, Vallier, control stem cells it may become Wutz, Chalut possible to correct these faults. Affiliate Investigators: Bertone, Bradley, Hemberger, Liu, Martinez-Arias, Reik, Rugg-Gunn, Stem cells could be used to renew Skarnes damaged tissues and replace missing cells in certain disorders. Neural Learning how to prevent a decline in Concepts regarding cell replacement numbers and activity of stem cells and regeneration in the adult may help to maintain health during mammalian central nervous system ageing. (CNS) have undergone a radical shift in recent years. This is due in part to Cambridge University has invested in the discoveries of continuous recruiting high quality investigators in neurogenic activity in distinct mammalian stem cell research at both anatomical regions and of a robust senior and junior levels. There are propensity for replacement of currently 26 mainstream stem cell oligodendrocytes that myelinate laboratories comprising more than 300 CNS axons. Nevertheless, the loss of group members including post-doctoral neurons remains a major clinical researchers and PhD students. challenge prompting a renewed effort in translational science aimed at prevention as well as replacement. Neuronal loss can Leading research scientists, technology occur as a result of (i) inherent defects, (ii) inflammation and (iii) specialists and doctors work side by loss of trophic support provided by myelinating cells. In this theme side to create a world-leading centre of we bring stem cell biology to bear all three causes in an integrated excellence in stem cell biology and programme of basic and translational research. medicine. The Institute also provides high level training for young Theme Leader: Franklin researchers from around the world and Principal Investigators: Barker, Karadottir, Kotter, Livesey, collaborates with bioindustry. Pluchino Affiliate Investigators: Ferguson-Smith, Martin, Stingl, Winton Core Facilities The following facilities support the research: Bioinformatics Flow Cytometry Histology Imaging Next Generation Sequencing Libraries Tissue Culture Tissue Samples Biomedical models 2 Haematopoiesis Environment Haematopoiesis represents the best The Centre for Stem Cell studied adult mammalian stem cell Research (CSCR) in the centre of system and provides paradigms for the Cambridge and the Laboratory mechanisms whereby normal stem for Regenerative Medicine (LRM) cells are subverted to form on the Addenbrooke’s Hospital malignancies. The goal of this theme is campus presently constitute twin to delineate the molecular and cellular bases for stem cell research and mechanisms regulating normal and translation. Stem cell groups are malignant haematopoiesis. A particular also housed in the Cambridge focus is our use of complimentary Institute for Medical Research approaches in human and murine (CIMR), Gurdon Institute, Centre systems. for Brain Repair (CBR) and other Departments. This distribution Theme Leader: Green reflects the intellectual diversity Principal Investigators: Gottgens, Huntly, Ottersbach, Warren of the Cambridge stem cell Affiliate Investigators: Ghevaert, Cvejic community and the breadth of institutional support. Solid Tissues The Wellcome Trust-Medical Research Council Cambridge Stem cells maintain the lifelong Stem Cell Institute (SCI) was renewal of epithelial tissues officially established on 1st July throughout the body. SCI investigators 2012, succeeding the former are studying the identity and Wellcome Trust Centre for Stem molecular regulation of stem cells in Cell Biology and the MRC Centre skin, intestine, lung and other epithelia for Regenerative Medicine. and analysing the dynamics of cell The Institute is supported by a behaviour in healthy and diseased strategic funding partnership states, including cancers. In contrast between the Wellcome Trust stem cells appear to play little or no and the Medical Research role in normal physiology of slowly Council. renewing tissues and organs such as the heart, liver and pancreas. Coalescence of basic stem cell However, pluripotent stem cells can be differentiated in vitro from research and translational these tissues, providing both a window into human development medicine is key to development and the opportunity for cellular disease modelling and drug of clinical applications. The development. Furthermore, production of tissue progenitors from University therefore is pluripotent stem cells creates the possibility of future cell constructing a new research replacement therapy for poorly regenerating organs. building to house the entire In the
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