ANNEX 2: MRC Epigenetics workshop - DELEGATE HANDBOOK MRC Epigenetics workshop 16 – 17 April 2015. The Oakley Court. Windsor. Berkshire. UK Scientific Steering Committee MRC Board experts Professor Mark McCarthy, University of Oxford (Chair) Dr Nessa Carey, PraxisUnico Professor Michael O’Donovan, Cardiff University UK and international experts Professor Stephan Beck, University College London Dr Jordana Bell, Kings College London Professor Anne Ferguson-Smith, University of Cambridge Professor John Greally, Albert Einstein College of Medicine, USA Professor Caroline Relton, University of Bristol Cover A wordle of the topics to be covered during this workshop. These topics have been derived from the responses posted by the delegates as part of the pre-workshop survey. Image credits: All delegates! 2 Table of Contents !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!' ) * !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!) & &*'%&), ' &+'%&)- $ !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!$$ ! "&' $ !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!$& ! "&( % !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!$( ! "&, % " !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!%$ ! "'' & !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!%' ! "'* !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!%* 3 4 Workshop background and aims Understanding the epigenetic mechanisms, their interactions and alterations in health and disease promises to make a significant contribution to the clinic. High- throughput technologies are enabling genome-wide epigenetic modifications to be mapped on an unprecedented scale. However, several challenges remain including whether such knowledge can be rapidly translated into biomedical applications. The MRC recognises that the UK has considerable strength in mechanistic (biochemistry), descriptive (genome wide) and functional (cell and model organisms) epigenetic research and better integration of these fields could present a big opportunity and address some of the challenges. This cross-Board workshop will aim to understand the existing gaps and review the emerging opportunities in epigenetics research; with a view to inform the MRC’s future strategy and help ensure that the balance of MRC investment in the area is appropriately aligned. Workshop format: pre-workshop survey Epigenetics is a vast and rapidly expanding field. To keep the workshop focussed on current and key strategic issues, all delegates were asked the following question: "Within your area of interest1, what are the 3 major challenges in the field of epigenetics, which if addressed appropriately, will present future opportunities in the short- to longer-term (5 - 10 years)" The survey responses were ‘sorted’ based on similarity2 and loosely grouped together to structure the workshop. We worked around these groupings to format the workshop such that it allows sufficient time to discuss the key issues in the field – as identified by the pre-workshop survey: Main sessions Breakout sessions Round table Expert talks Group discussions, Summarising and introducing key further exploring the agreeing on key issues and issues identified recommendations to challengeslenge during main sessions inform future strategy - 2 plenaryl sessions (Setting the scene, Functional epigenomics) - 3 topical sessions (Mechanisms, Drivers of epigenetic variations, Epigenetics and disease) 1 this may include all methodological fields, for example; experimental, computational, statistical epigenetics and epi-genomics 2 using the automated survey and visualisation platform, Wellsorted (well-sorted.org) 5 Pre-workshop survey outcomes: An overview Below is an overview of the responses (titles only) submitted by the delegates, grouped under the relevant sessions. Corresponding descriptions are listed in session specific sections, to provide context. Each response has been given a unique number so they are easier to find. Session 2: Causes and Plenary 1: Setting the scene consequences of epigenetic variation 1. Retroelements 2. Function of the epigenome 3. Human Epigenomics 31. Proof of causality 4. Use of whole blood epigenetic 32. 'Signatures' of social and profiling in EWAS behavioural experiences 5. DNA and RNA epigenome: 33. Pathways from experiences to complexity and interplay epigenome 6. Higher-order chromatin 34. Health and behavioural structure consequences of epigenetics 7. Methylation vs other types of 35. Ageing epigenetics epigenomic data 36. Environment versus 8. We need to talk about EWAS transcription factors 9. Distinguishing biologically 37. Approaches from determining significant changes cause from effect 10. Targets of Histone Modifying 38. Genetic-epigenetic- environmental variation 39. Disease cohorts, epidemiology and functional assay Session 1: Focus on mechanisms 40. Stem cells and Epigenetics 41. Metabolism and Epigenetics 11. Identifying high-confidence 42. Maternal nutrition and offspring epigenetic changes epigenome 12. Molecular cell classification 43. Effects of epigenome on 13.Epigenetic Inheritance function 14.Transgenerational epigenetic 44. Ascribing function to inheritance epigenomes 15.Peripheral tissues as a proxy for 45. Integrating metabolism, internal organs signaling and epigenetics 16.Transgenerational epigenetic 46. Dietary effects on the inheritance epigenome 17.Epigenetic diversity and cell fate 47. Identifying cause and effect decisions 48. Are epigenetic changes 18. Transgenerational effects instructive? 19.Trans-generational inheritance 49. Encouraging strengthening 20. Identifying a mechanism for causal inference heritability 50. Causal inference 21. How is DNA demethylated 51. Epigenetic information, 22.Addressing tissue specificity environment and disease 23. Neurodisorders:map & validate 52. Epigenetic causality (epi)genetic network 53. Causality 24. Epigenetic memory 54. Cause and effect 25.Tissue and cellular specificity 55. Markers of exposure 26.Brain and periphery 56. The meaning of epigenetic 27. Tissue specificity markers 28.Understanding cellular responses 57. Epigenetics and other omics 29. Stability and heterogeneity 58. Epigenetics and environmental 30.Are the changes stable? exposure 59. Cause or effect 6 Plenary 2: Functional Session 3: Epigenetics and epigenomics – a critical disease evaluation 83. Targeted 60. Precision (smart) medicine reprogramming 61. Cellular heterogeneity and 84. Epigenetic single-cell analysis interventions 62. Single cell technology 85. Development and 63. Single cell and single disease molecule technologies 86. Chemical Probes 64. Histone Epigenomics 87. Functional role of 65. Sample Collection epigenetic biomarkers 66. Bioinformatics 88. Genetics and disease 67. Data crunching capacity drivers and 68. Increasing the coverage of combinations epigenomic data 89. Understanding the 69. Single cell ChIP-Seq consequences of 70. Locus Specific ChIP-seq / disease changes proteomics 90. Translating epigentic 71. Single-cell epigenomics changes into 72. Detection of epigenetic biomarkers marks in single cells 91. Epigenetic changes 73. Technologies for population and cancer based studies progression 74. Functional follow-up of 92. Epigenetic epigenetic signals neurodevelop. 75. In-vivo chromatin structure disorders - animal - nucleosome position models 76.Sequencing 93.Translational potential 77. Technologies for measuring of epigenetic markers methylation 94. Translational potential 78. Data visualisation from of epigenetic markers epigenome to phenome 95. Manipulation 79. Gaps in epigentic 96. Identifying predictive methodology biomarkers 80. Emerging technology for 97. Epigenetics and drugs functional epigenetics 98. Reprogramming 81. Combinatorial Nucleosome 99. Do they matter? Modifications 82. Structures of Chromatin- Associating Complexes 7 Agenda Day 1, Thursday 16th April 2015 09:30 Registration open. Networking tea/coffee 11:00 Welcome and workshop context Professor Mark McCarthy, University of Oxford, UK 11:15 Plenary Day 1: Setting the scene - Interpreting the epigenetics landscape Dr Gavin Kelsey, The Babraham Institute, UK - Interpreting the results of Epigenome-Wide Association Studies Professor John Greally, Albert Einstein College of Medicine, USA 12:15 Session 1: Focus on mechanisms - Trans-generational inheritance Professor Vardhman Rakyan, The Blizard Institute QMUL, UK - Epigenetic heterogeneity in cells Professor Jonathan Mill, University of Exeter Medical School, UK - What can we learn from animal models? Professor Eric Miska, Gurdon Institute, UK 13:15 Networking lunch 14:00 Session 1 continues (breakout group discussions3) 14:50 Session 2: Causes and consequences of epigenetic variation - Genetics, epigenetics & the environment Dr Jordana Bell, Kings College London - Population epigenetics and causal inference Professor Caroline Relton, University of Bristol 15:40 Afternoon tea break 16:00 Session 2 continues (breakout group discussions) 16:50 Workshop mixer 17:30 – 18:30 Round table Day 1 19:30 Dinner 8 Day 2, Friday 17th April 2015 Chair welcome and context for Day 2 09:00 Professor Mark McCarthy, University of Oxford, UK 09:15 Plenary Day 2: Functional Epigenomics – a critical evaluation - Critical evaluation