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Title: Robert Beagrie — Radcliffe Department of Medicine
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Texto: Robert Beagrie — Radcliffe Department of Medicine Cookies on this website We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings. Continue Find out more Site Map Accessibility Cookies Contact us Log in Home About us About us Our Divisions Our Clinical Facilities and MRC Units Working at RDM Athena SWAN News Seminars Locations and contact details Research People Study with us Work with us Current vacancies Novo Nordisk - Oxford Fellowships For Staff Contacts, travel and maps Personnel Finance, Grants and Funding Facilities, IT and Health and Safety Graduate Studies Career Development Athena SWAN Communications and public engagement Search People Robert Beagrie Contact information Email robert.beagrie@ndcls.ox.ac.uk Research groups Higgs Group: Laboratory of Gene Regulation Colleges Somerville College Robert Beagrie PhD Postdoctoral Scientist Sir Henry Wellcome Postdoctoral Fellow at the MRC Weatherall Institute Fulford Junior Research Fellow at Somerville College Advanced Python for Bioinformatics Due to the shutdown of the WIMM by COVID-19, I will be running the "Advanced Python for Bioinformatics" course online using datacamp (https://www.datacamp.com/ ). The course is open to all DPhil students at the WIMM and will begin on Monday April 6th. Further details will be circulated via email. I am a Sir Henry Wellcome Postdoctoral Fellow working with Prof. Doug Higgs in the MRC Haematology Unit on regulatory regions of DNA called enhancers and how they function to regulate gene expression. I studied Biochemistry as an undergraduate at Cambridge University and completed my PhD at Imperial college supervised by Prof. Ana Pombo, who subsequently moved to the Max Delbruck Centre in Berlin. Genome Architecture Mapping (GAM) For my Doctoral project, I developed Genome Architecture Mapping (GAM), a new technology for measuring the complex folding of DNA in the 3D space of the nucleus. GAM works by isolating hundreds of thin slices from individual nuclei and sequencing their DNA content. Genomic regions which are close in the nucleus will be found together in the same thin nuclear slice more often than regions which are distant. Importantly, this approach is readily applicable to fixed tissue, and could therefore be an important tool for identifying the targets of sequence variants implicated in human disease. To test this new method, I applied GAM to mouse embryonic stem (mES) cells by sequencing DNA from around 500 mES nuclear slices and generating a map of DNA folding. In collaboration with Dr. Antonio Scialdone and Prof. Mario Nicodemi (University of Naples) we developed a statistical model to identify DNA regions that interacted in threes, rather than in pairs. Remarkably, we found thousands of triplets throughout the mES cell genome, suggesting that multi-way contacts are a prevalent and potentially important feature of chromatin folding. By searching for common features, we found that triplets are especially likely to form between the strongest enhancers, so-called super-enhancers1 . GAM holds the potential to detect enhancer-gene interactions in rare cell types that are currently difficult to study using alternative approaches. Many of these rare cells are affected in genetic disease, and the ability to connect sequence variants to the genes whose expression they affect will provide new insights crucial for developing diagnostic and therapeutic interventions. Enhancer function in erythropoiesis Whilst working on GAM I developed a passion for enhancer biology and a keen interest in the mechanism by which enhancers activate expression of their target genes. My Sir Henry Wellcome Postdoctoral Fellowship project aims to dissect the mechanisms driving gene activation by enhancers during red blood cell differentiation. The project began in April 2018 and will be carried out in collaboration with Assoc. Prof. Merav Socolovsky (UMass Medical School). The Socolovsky Lab has identified an intriguing transition point during mouse red blood cell differentiation in which early red blood cell progenitors begin replicating their DNA at precisely the same moment that they activate many genes required for their terminal differentiation2 . Cells also replicate DNA faster during this specific cell cycle than the cycles that precede or follow it3 . My project will identify the genes activated during this transition and the enhancers that regulate them by using global approaches to measure changes in DNA folding, binding of regulatory proteins to enhancers and gene activity. Applying these approaches to a gene activation event that occurs during a single cell cycle will give me unique temporal precision. References 1. R. A. Beagrie et al. , Complex multi-enhancer contacts captured by genome architecture mapping. Nature . 543 , 519–524 (2017). 2. R. Pop et al. , A Key Commitment Step in Erythropoiesis Is Synchronized with the Cell Cycle Clock through Mutual Inhibition between PU.1 and S-Phase Progression. PLoS Biol. 8 , e1000484 (2010). 3. Y. Hwang et al. , Global increase in replication fork speed during a p57 KIP2 -regulated erythroid cell fate switch. Sci. Adv. 3 , e1700298 (2017). Recent publications Dynamics of the 4D genome during in vivo lineage specification and differentiation. Journal article Oudelaar AM. et al, (2020), Nat Commun, 11 Dissection of the 4D chromatin structure of the α-globin locus through in vivo erythroid differentiation with extreme spatial and temporal resolution Journal article Oudelaar M. et al, (2019) Modelling erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I) Journal article Scott C. et al, (2019) Hypoxia induces transcriptional and translational downregulation of the type I interferon (IFN) pathway in multiple cancer cell types Journal article Miar A. et al, (2019) Cell cycle: Continuous chromatin changes. Journal article Beagrie RA. and Pombo A., (2017), Nature, 547, 34 - 35 More publications ORCID 0000-0003-1076-5595 © 2020 Radcliffe Department of Medicine Freedom of Information Privacy Policy Copyright Statement Accessibility Statement Site Map Accessibility Cookies Contact us Log in About us Our Divisions Investigative Medicine Division Nuffield Division of Clinical Laboratory Sciences Oxford Centre for Diabetes, Endocrinology and Metabolism Division of Cardiovascular Medicine MRC Weatherall Institute of Molecular Medicine MRC Weatherall Institute of Molecular Medicine Our Clinical Facilities and MRC Units Acute Vascular Imaging Centre Cardiovascular Clinical Research Facility Oxford Centre for Clinical Magnetic Resonance Research Working at RDM Equal career opportunities and flexible working Career development and training Athena SWAN News Seminars Locations and contact details Research Cardiovascular Science Haematology and Pathology Diabetes, Metabolism and Endocrinology Cancer Biology Immunology and Infection Stem Cells and Developmental Biology Geratology Experimental Therapeutics Ashrafian Group: Experimental Therapeutics and Clinical Pharmacology Mahmod group Tyler Group Lunter Group: Functional Genomics & Machine Learning Lunter Group Chapman Group: Genome stability and DNA repair mechanisms in cancer and genome diversification Patel Group People Moustafa Abdalla Ines Abdesselam Adib Abdullah Amanda Adler Satish Adwani Devika Agarwal Olorunsola Agbaje Doaa Ahmed Jila Ajeian Nadia Akawi Naveed Akbar Nasren Akhtar Ioannis Akoumianakis Merve Aksoz Marta Perez Alcantara Yara Alenazi Affaf Aliouat Jack Allen Maryam Alsharqi Sneha Anand Amanda Anderson Agata Antepowicz Charalambos Antoniades Alex Antonopoulos Mahesh Appari Andrew Apps Janhavi Apte Rina Ariga Andrew Armitage Alyssa Armsby Linda Arnold Ritu Arya James Ashford Neil Ashley Nicole Ashman Houman Ashrafian Kate Attfield Christian Babbs Mohsin Badat Ileana Badi Jade Bailey Subita Balaram Abhirup Banerjee Alison Banham Adrian Banning Liliana Barbieri Mike Barnkob Amy Barrett Matthew Baxter Asha Bayliss Robert Beagrie Daniel Beard Jordan Becker John Bell John Bell Elena Benedetto Amanda Bennett Felicity Bennett Timothy Betts Ryan Beveridge Shoumo Bhattacharya William Biggs Malenka Bissell Edward Blair Henry Blest Nicholas Blockley Henry Boardman Andrea Borghetto Alessandra Borlotti Jacqueline Boultwood Yavor Bozhilov Adam Braithwaite Robert Brand Matt Brechin Serena Briant Linford Briant Anne Bridgeman Paul Brodersen James Brown Jill Brown Lynn Brown Connor Broyles Marella de Bruijn Alastair Buchan Veronica Buckle Paul Buckley Daniel Bulte Martijn van de Bunt Mario Buono Holger Burchert Emma Burke-Smith Oliver Burns Matthew Burrage Shijie Cai David Cain Sarah Califano Ivan Candido-Ferreira Fang Cao Maria Carena Maria Carena Ricardo Carnicer Davide Carone Joana Carrelha Brigid Carter Barbara Casadei Carla Cascone Kuan Cha Hedia Chagraoui Jem Chalk Keith Channon Ross Chapman Lise Chauveau Jane Cheeseman Yi-Ling Chen Jili Chen Qian Cheng Amy Chiu Robin Choudhury Constantinos Christodoulides Zoe Christodoulou Sandy Chu Surawee Chuaiphichai Aldo Ciau-Uitz Thomas Clague Sally-Ann Clark Kevin Clark Lynn Clee Liz Cloke Christopher Cole Ruth Coleman Huw Colin-York Michela Colombo Ismael da Conceicao Catriona Conway Daniel Cooke Kerrie Cope Anna Corby Thomas Cornfield Eduardo Calpena Corpas Yvonne Couch Mark Crabtree Fay Croft Heidi Crook Eloise Cross Nicholas Crump Andres Hueso Cuervo Nicola Curry Melinda Czéh Liangti Dai Andrea van Dam Rinita Dam Matt Daniels Lorna Daniels Carol Davey James Davies Graham Davies Simon Davis James Dean Rebecca Dean Atanasiu Stefan Demian Niall Dempster Louise Dennis Timothy Dent Geoffrey Denwood Michael Desborough Matthew Dickinson Marina Diotallevi Tomasz Dobrzycki Cameron Dockerill Michael Dodd Kathleen Dolan


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246 www.rdm.ox.ac.uk/people/rinita-dam
247 www.rdm.ox.ac.uk/people/matthew-daniels
248 www.rdm.ox.ac.uk/people/lorna-daniels
249 www.rdm.ox.ac.uk/people/carol-davey
250 www.rdm.ox.ac.uk/people/james-davies
251 www.rdm.ox.ac.uk/people/graham-davies
252 www.rdm.ox.ac.uk/people/simon-davis
253 www.rdm.ox.ac.uk/people/james-dean
254 www.rdm.ox.ac.uk/people/rebecca-dean
255 www.rdm.ox.ac.uk/people/atanasiu-stefan-demian
256 www.rdm.ox.ac.uk/people/niall-dempster
257 www.rdm.ox.ac.uk/people/louise-dennis
258 www.rdm.ox.ac.uk/people/timothy-dent
259 www.rdm.ox.ac.uk/people/geoffrey-denwood
260 www.rdm.ox.ac.uk/people/michael-desborough
261 www.rdm.ox.ac.uk/people/matthew-dickinson
262 www.rdm.ox.ac.uk/people/marina-diotallevi
263 www.rdm.ox.ac.uk/people/tomasz-dobrzycki
264 www.rdm.ox.ac.uk/people/cameron-dockerill
265 www.rdm.ox.ac.uk/people/michael-dodd
266 www.rdm.ox.ac.uk/people/kathleen-dolan



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