To study epigenetic mechanisms regulating lineage commitment and cell potency

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

This objective is a natural progression of our previous ISPG in which we have successfully established epigenomic profiles across a vast array of developmental stages during germ cell as well as pre- and post-implantation development, and of related stem cell types. We shall build on these advances and address key questions arising: notably, how are distinct, cell type-defining epigenetic patterns established at the mechanistic level to cement cell fate specification and, conversely, what are the critical chromatin features that enable the reversal to totipotency? Mathematical modelling integrating transcriptional, epigenetic and metabolic states will provide a quantitative mechanistic understanding of the control mechanisms underlying toti-/pluripotency, self-renewal and lineage differentiation pathways. Developmental progression is characterised by the transition of cellular plasticity from a totipotent zygote to the emergence of the first cell lineages at the blastocyst stage and ultimately the differentiation into highly specialised cell types. These steps are underpinned by the acquisition of epigenetic marks that help define, and lock in, cell fate. As such, totipotency is an ephemeral state intrinsic only to the fertilised zygote and 2-cell stage embryo, and describes the widest-possible plasticity of a cell to differentiate into all embryonic as well as extra-embryonic cell types. Despite its importance, little is known regarding the molecular mechanisms regulating this state, mostly due to limited and hard-to-obtain samples. However, the recent identification of a small subpopulation of embryonic stem cells (ESCs) that exhibits totipotent features (so-called 2C-like cells), together with transformative advances in single-cell technologies, has opened up this field to mechanistic investigations. Leading on from this, our work has shown that the timing of lineage commitment coincides perfectly with the onset of de novo DNA methylation, and results in the establishment of lineage-defining epigenomic patterns and hallmarks1-3. We have also explored how the epigenome integrates with the transcriptional landscape and how it is influenced by signalling pathways4,5. With this in-depth knowledge, a critical question is how the epigenetic machinery is targeted to different genomic sites to set up lineage-distinctive and cell potency-defining patterns. In parallel with experimental efforts, we will expand our modelling approaches of the first cell fate decision by integrating transcriptional, epigenetic as well as metabolic data to gain qualitative and quantitative insights into the regulators governing totipotency and cellular differentiation. Cellular metabolism is known to differ between the first cell lineages, in particular lipid metabolism, and metabolic state is recognised as an important modulator of cell plasticity that may thereby impact on the epigenome. Thus, integration of cell metabolic states into mathematical models, in parallel to our experimental efforts, will advance our understanding of how the epigenome is shaped to promote self-renewal and underpin the first cell fate decision events. This Objective involves close cross-ISP interactions with the Signalling ISP in relation to trophoblast stem cells (TSCs) and modelling of metabolic effects on epigenetic regulators on cell-fate decisions.

Publications

10 25 50
 
Description We have made significant progress in our aim to dissect the molecular mechanisms and players that control totipotency and cell fate decision-making during early mammalian development.
2C like cells are transcriptionally and epigenetically similar to the two-cell stage embryo. We discovered two new positive regulators of 2C like cells and zygotic genome activation (ZGA): Dppa2 and Dppa4 ((PMID 30692203). Through a combination of knockout, knockdown, overexpression and rescue experiments, we were able to dissect the molecular hierarchy that underpins the 2C-like transcription programme. We could show that loss of DNA methylation at the Dppa2 and Dppa4 promoters temporally correlates with Dppa2 and Dppa4 expression (Objective 1.1.1). Further, Dppa2/4 directly bind to the Dux promoter to induce Dux expression. This establishes a 2C-like transcription programme that is subsequently stabilised by Zscan4c (Objective 1.1.2).
We have also identified proteins with key functions in maintaining the cellular identity of stem cells during early mammalian development. Our data have revealed essential functions for the TET proteins in the trophoblast lineage (Objective 1.2). We uncovered a novel role for TET1/2 proteins in the control of trophoblast cell cycle progression (PMID 29576538), and in mediating throphoblast-specific long-range chromosomal interactions involved in the regulation of key trophoblast genes (PMID 30305613). By contrast, key trophoblast genes are repressed in embryonic stem cells by long-range chromosomal interactions orchestrated by the epigenetic regulators of the Polycomb group complexes (PMID 30305613; Objective 1.2.2).
We have further extensively used the cutting-edge single cell methodology developed in our ISP to functionally characterise cell lineages during early mouse and human development. Building on our expertise developed in this grant to isolate pure populations of human naïve and primed pluripotent stem cells, we have characterised, at the single cell level, the expression signatures for both cell types representing key stages of early human embryonic development (PMID 30673604; Objective 1.2).
Parallel single cell analysis and epigenetic profiling has revealed oscillatory dynamics during the exit from pluripotency (PMID 30031774), indicating that dynamic changes in DNA methylation might underpin cell fate decisions during early mammalian development (Objective 1.2).
By profiling the transcriptome of over 100,000 individual cells, we have contributed to constructing a comprehensive, single cell-resolution atlas of transcriptional events that define cell states during early mouse development (PMID 30787436; Objective 1.2). Taking advantage of methodology developed in our department, we are now linking these transcriptional events to changes in chromatin accessibility and DNA methylation during embryonic cell lineage specification at single cell resolution (Objective 1.2.1).
Screening mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders programme, we found that over two thirds of mouse lines that are lethal at or after mid-gestation exhibit abnormal placental morphologies. We demonstrated that unexpectedly, placental defects strongly correlate with defects in heart, brain and vascular development. Our data have thus uncovered a hitherto unrecognised contribution of placental abnormalities to embryonic development (PMID 29539633; Objective 1.2).
Exploitation Route Our research is uncovering novel players that direct cellular plasticity and that underpin cell fate decisions in development, thereby advancing the 'Bioscience for Health' BBSRC priority. We are disseminating our research through scientific publications, presentations at international meetings and organisation of conferences (e.g. The Ageing Cell, 2017; ESHRE 2017; EMBL Mammalian Genetics and Genomics Meeting 2017; etc). We are providing high-level training to others in using the technologies we developed and in the concepts we discovered, which fundamentally promotes UK's reputation and standing in conducting pioneering science research. The Epigenetics ISP is showcasing its research at the Cambridge Science Festival and Royal Society Summer Festival (exhibit 'Race Against The Ageing Clock'). We are also contributing to the creation of an informed society through taking part in public events about epigenetics, development, stem cells, ageing, and gene editing (e.g. at the Cambridge Science Festival, in Q&A sessions with the public etc).
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description We have developed, in collaboration with former members of the Nuclear Dynamics ISP, a Virtual Reality (VR) project that enables members of the public to experience the three-dimensional folding of DNA in the nucleus in a novel and 'hands-on' way. This project ('Chromos: A virtual DNA experience') has successfully featured during the Cambridge Science Festival in February 2017, at the London Science Museum Lates in September 2017, and in 2018 as part of the 'Open Codes' exhibit at ZKM (Centre for Art and Media) in Karlsruhe, Germany. For Chromos, 3D genome folding data generated at the Babraham Institute have been transformed into a VR experience (by visual artist and mathematician Andy Lomas), accompanied by a soundtrack composed by musician Max Cooper. Chromos allows people to interact with the data in a unique way by 'climbing inside the data'. CHROMOS has been very well received by members of the public, which convinced us that VR is an ideally suited medium to present and explain the significance of our research (in particular involving complex three-dimensional biological structures) to a wider public. It also presents a great opportunity for two-way engagement with the public, to capture their feedback. For the future, we plan to further develop CHROMOS to incorporate 3D genome folding data generated during the Epigenetics ISP, including the comparison of the 3D genome organisation between mouse embryonic stem cells and trophoblast cells (PMID: 30305613; Objective 1.1) and human naïve and primed pluripotent stem cells (Objective 1.2).
First Year Of Impact 2017
Sector Education,Healthcare
Impact Types Societal

 
Description CTR Board of Managers (MH)
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
Impact Member, Board of Managers of the Centre for Trophoblast Research, Cambridge assessing funding for targetted PhD studentship and Next Generation fellowship applciations and influencing science strategy within this research area.
 
Description Chair of SAB Centre for Trophoblast Research University of Cambridge
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Has changed the perception of placenta and trophoblast in reproduction
 
Description H2020 EU-LIFE project "LIBRA", co-lead work package "Gender Equality in Research"
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
Impact Consideration of gender effects in research, appreciation that there may be sex differences in cell lines, animal models and treatment regimes that ought to be taken into consideration when designing studies.
 
Description Review panel member, DFG Clinical Research Unit (Germany) (MH)
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
Impact Funding assessment for a major research unit on male infertility which includes improvement of patient treatment options and better patient assessment and stratification. Funding was recommended by teh panel and was implemented.
 
Description Steering board Human Cell Atlas
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description Flagship
Amount € 1,000,000 (EUR)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 02/2019 
End 03/2020
 
Description Investigator Award
Amount £2,600,000 (GBP)
Funding ID 210754/Z/18/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2018 
End 09/2023
 
Description Special initiative
Amount £10,000,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2019 
End 04/2024
 
Description UKRMP2 Pluripotent Stem and Engineered Cell (PSEC) Hub
Amount £250,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Title C elegans Metabolic Reconstruction Model 
Description Merged and re-annotated C elegans Metabolic Reconstruction Model 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? Yes  
Impact This is a great improvement to the C elegans research community 
 
Title PCR Bayes 
Description Novel algorithm to quantify expression and biological variability of steady state transcripts 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? No  
Impact This is a novel tool which extends the capabilities of C elegans researchers to quantitate biological noise in single worms 
 
Title Parp1/2 knockout 
Description Established mouse knockout lines that lack Parp1 and Parp2. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact Possibility to study impact of these genes on imprinted gene regulation, the stability of chromatin organisation in general, and DNA damage responses. 
 
Title Pigl and Pigf mutant TSCs 
Description Generated and established trophoblast stem cell lines lacking either Pigl or Pigf. 
Type Of Material Cell line 
Year Produced 2017 
Provided To Others? No  
Impact Mutant TSC lines being analysed at present for the impact of the gene mutation on self-renewal and differentiation capacities. 
 
Title Tet mutant TSCs 
Description Generated and established trophoblast stem cell lines lacking either Tet1, Tet2 or Tet1+Tet2. 
Type Of Material Cell line 
Year Produced 2017 
Provided To Others? No  
Impact Enabling the assessment of the role of TET enzymes, and their product 5-hydroxymethylcytosine, on trophoblast stem cell maintenance, integrity and differentiation. 
 
Title Aging Cell 2018 
Description We provide expression (RNA-seq) and epigenetic (ChIP-Seq and BS-Seq) data sets for young adult and aged mouse neural stem cells. The data are accessible at GEO under Accession Number GSE101610. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact We anticipate that other researchers will use our published data sets to identify candidate regulators of age-associated neurogenic decline. 
 
Title Cell Stem Cell 2017 
Description We have deposited RNA-sequencing data related to our publication in Cell Stem Cell, 2017. The data have been uploaded to GEO under accession number GSE93241. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact The data relate to the reprogramming of human pluripotent stem cells. We anticipate that these data will be used by other researchers. 
 
Title ChIP-seq profiles for Tet1 in TSCs (GSE109545) 
Description Chromatin binding profiles of Tet1 protein in trophoblast stem cells (TSCs) 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact Data allow to determine the functional role of Tet1 in TSCs 
 
Title ChIP-seq profiles for numerous transcription factors in TSCs (E-MTAB-3565) 
Description Chromatin binding profiles for Esrrb, Tfap2c, Lsd1, Nr0b1 and others in TSCs 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? No  
Impact Datasets were deposited in publicly available databases. Results helped identify the transcriptional networks operational in trophoblast stem cells, the precursors of the placenta. These insights will be immensely useful for other researchers in the field. 
 
Title Elf5 and Esrrb protein interactomes in TSCs (PXD002183) 
Description IP->MS/MS datasets of interaction partners of the key transcription factors Esrrb and Elf5 in trophoblast stem cells (TSCs). 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? No  
Impact Data deposited in publicly accessible databases. Results are instrumental to gain a detailed understanding of how TSCs operate, which will be important to move the field of reproductive biology and pregnancy (normal and pathological) forward. 
URL http://www.ebi.ac.uk/pride/archive/
 
Title Profiling of epigenetic reprogramming between ESCs, MEFs and TSCs 
Description DNA methylation profiles of various ESC->TSC reprogramming models, as well as MEF->TSC reprogramming. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Datasets are deposited in publicly accessible databases. Findings show that an epigenetic memory is retained when reprogramming from ECSs, but less so when MEFs are used as starting material. 
 
Title Stem Cell methylomes 
Description DNA methylation (meDIP)-seq profiling of ESCs, TSCs, XEN cells and EpiSCs 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Data were deposited in publicly accessible databases. Data will be useful to many other researchers for meta-analyses. 
 
Title Transcriptome datasets of reproductive tissues in ageing females (GSE98901) 
Description RNA-seq datasets of trophoblast, endometrium and deciduae of mouse conceptuses developed in young versus aged females 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact Significant changes imposed by maternal age on expression profiles of endoemtrial tissue and decidual development. Work shows the impact of the older female on reproductive success, unrelated to oocyte fitness. 
 
Title Webtool for integration of high-throughput datasets and their rapid analysis 
Description Generation of a webtool allowing rapid data analysis of high-througput sequencing datasets. 
Type Of Material Computer model/algorithm 
Year Produced 2018 
Provided To Others? No  
Impact Webtool allows to upload and integrate multiple datasets of different nature (such as ChIP-seq, RNA-seq, DNA methyaltion profiles) and allows to perform rapid multivariate analyses on them to find co-occpuancy, mutual exclusion etc 
 
Title eLife 2017 
Description High-through sequencing data related to our 2017 published in eLife. Data deposited in GEO under accession number GSE86821 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact We provide the coordinates for promoter-enhancer interactions in human pluripotent cells and differentiated cells. The data will be re-used by other researchers. Too early for measured impacts. 
 
Description Active Motif DNA modification antibody 
Organisation Active Motif
Country United States 
Sector Private 
PI Contribution Commercialisation of DNA modification antibodies we have made
Collaborator Contribution Commercialisation of DNA modification antibodies we have made
Impact Commercially available antibodies
Start Year 2016
 
Description CEGX 
Organisation Cambridge Epigenetix
PI Contribution Data generated by CASE PhD student as preliminary/pilot data for target validation of epigenetic changes in disease.
Collaborator Contribution Industrial CASE PhD studentship partner Cambridge Epigenetix (CEGX) provided help and advice in novel, proprietary technique and enabled student to perform this new method of epigenetic target validation during the placement period.
Impact PhD studentship in progress. Manuscript(s) will be generated from this work, possibly even targets for follow-on work and potential commercialisation as epigenetic biomarkers.
Start Year 2016
 
Description Collaboration with Fredrik Lanner 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution Help and assistance with multi-omics single cell sequencing and computational analysis
Collaborator Contribution Collection of human embryo cells
Impact Paper is in preparation. Embryology, single cell genomics, computation.
Start Year 2017
 
Description Collaboration with James Turner 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We are providing help and training with scNMT-seq
Collaborator Contribution Collected samples from marsupial embryos for sequencing
Impact None yet
Start Year 2018
 
Description Deciduoma 
Organisation National Institute of Environmental Health Sciences
Department Reproductive and Developmental Biology Laboratory
Country United States 
Sector Public 
PI Contribution Characterisation of reproductive defects in older females
Collaborator Contribution Decidualisation model to assess the effect in the absence of an implanting embryo
Impact Collaborative publication (PMID: 28874785)
Start Year 2016
 
Description Greg Findlay - Biochemistry of DNMT1 and UHRF1 and demethylation 
Organisation University of Dundee
Department National Centre for Protein Kinase Profiling
Country United Kingdom 
Sector Academic/University 
PI Contribution We have purified proteins and sent them to Greg Findlay's lab for proteomics and phosphoproteomics
Collaborator Contribution They have identified several phosporylation sites of interest
Impact Biochemistry, genetics, epigenetics, developmental biology
Start Year 2018
 
Description Neil Brockdorff - X chromosome inactivation 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution We helped with DNA methylome sequencing and analysis
Collaborator Contribution Contributed relevant samples for sequencing
Impact See publications. Biochemistry, cell biology, epigenomics, computational biology.
Start Year 2016
 
Description Shankar Balasubramanian - nucleosome positioning depending on DNA modifications 
Organisation University of Cambridge
Department Cancer Research UK Cancer Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided embryonic stem cell and mouse embryo samples
Collaborator Contribution Analysed nucleosome positioning in samples provided by our lab
Impact See publications. Chemistry, biochemistry, developmental biology, epigenomics.
Start Year 2016
 
Description TET interactome 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Establish Tet1 binding profile in TSCs
Collaborator Contribution Analyse data in an integrated fashion together with 3D structural organisation data of DNA in TSCs
Impact Manuscript in preparation
Start Year 2017
 
Description Thorsten Boroviak - single cell multi-omics of primate development 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Carrying out single cell multi-omics on samples from non-human primates
Collaborator Contribution Providing samples from non-human primates
Impact See publications. Developmental biology, epigenomics, computational biology.
Start Year 2017
 
Description Trophoblast Stem Cells 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Generation of locus-specific DNA methylation profiles to confirm lineage identity of derived cells.
Collaborator Contribution Establishment of an organoid system that promotes the maintenance of human trophoblast stem/progenitor cells.
Impact Publication in process. This collaboration is multi-disciplinary between pathologists, physiologists and us as epigeneticists, it also involved bio-engineering helping in the design of microfluidics devices.
Start Year 2017
 
Description XIMBIO DNA modification antibodies 
Organisation Cancer Research Technology (CRT)
Country United Kingdom 
Sector Private 
PI Contribution Commercialisation of DNA modification antibodies we have made
Collaborator Contribution Commercialisation of DNA modification antibodies we have made
Impact DNA modification antibodies
Start Year 2016
 
Description single cell TSCs 
Organisation University of Cambridge
Department Department of Obstetrics & Gynaecology
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration with Prof Steve Charnock Jones to form core of Centre of Trophoblast Research single cell transcriptomics profiles of mouse (and human) trophoblast stem cells under various conditions, as well as of placentas. Provided cells and tissues and culture media components to collaborator.
Collaborator Contribution Set up Drop-seq and optimising technique for nuclear RNA sequencing, required for syncytia. Performed sc-RNA-seq.
Impact Manuscript in preparation.
Start Year 2017
 
Description uNK cells 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Characterisaiton of reproductive problems in older females.
Collaborator Contribution Analysis of immune repertoire of implantation sites depending on maternal age.
Impact Collaborative publication (PMID: 28874785).
Start Year 2016
 
Description BBSRC Institutes Collaborative Workshop on Epigenetics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact BBSRC Institutes Collaborative Workshop on Epigenetics
Babraham Institute, Cambridge, UK (November 2018)
Year(s) Of Engagement Activity 2018
 
Description Babraham Schools day 2018 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Experiments on epigenetics for local 6th form schools
Year(s) Of Engagement Activity 2018
 
Description Cambridge Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Babraham Institute exhibit on the Epigenetic Ageing Clock presented at the Cambridge Science Festival, involving activities and question/answer interactions with members of the public
Year(s) Of Engagement Activity 2018
 
Description Cambridge Science Festival: Molecular Explorers, Cambridge (UK) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Exhibit at Cambridge Science Festival, engaging with visitors at stall explaining the science and advances made in the area, answering questions and discussing outstanding research goals
Year(s) Of Engagement Activity 2017
 
Description Cold Spring Harbor Laboratory meeting: Stem Cell Biology, New York (USA) (VPG, CS) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Participation in confenrence, poster presentation by both post-doctoral reserachers involved in this activity (VPG and CS) and engagement in discussions and broadening of scientific horizon
Year(s) Of Engagement Activity 2017
 
Description Computational Modeling in Biology Network 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I created COMBINE to coordinate the development of standards in computational systems biology. The initiative includes several workshops a year (discussion of future standards, implementation of current standards, and end-user training), diffusion lists, social media dissemination.
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015
URL http://co.mbine.org
 
Description EMBL Mammalian Genetics and Genomics Conference (MH) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited speaker at AMBL Conference Mammalian genetic and Genomic, Heidelberg, Germany
Year(s) Of Engagement Activity 2017
 
Description EMBL-EBI Industry Programme Workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Epigenetics for Aging and Disease
EMBL-EBI Industry Programme Workshop
European Bioinformatics Institute, Cambridge, UK (November 2018)
Year(s) Of Engagement Activity 2018
 
Description EU-Life meeting Principles of Homeostasis, Berlin (Germany) (VPG) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Participation and poster presentation at EU LIfe meeting "Principles of Homeostasis" held in Berlin, Germany (2017)
Year(s) Of Engagement Activity 2017
 
Description GENIE network of C elegans researchers 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Joining this pan european network has allowed us to attend conferences, network with other C elegans labs across Europe and obtaining funding to organise a workshop on C elegans metabolic reconstruction.
Year(s) Of Engagement Activity 2015,2016,2017,2018
 
Description GENiE workshop "Extending the consensus representation of C. elegans metabolism" 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact https://www.helmholtz-muenchen.de/genie-workshop-2017/program/index.html
Year(s) Of Engagement Activity 2018
URL https://www.helmholtz-muenchen.de/genie-workshop-2017/program/index.html
 
Description General public workshop "Cambridge Climate and sustainability festival" 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Invited speaker at "Cambridge Climate and sustainability festival" at St John's college February 16th, 2019
Year(s) Of Engagement Activity 2019
 
Description Genetics Society and BSDB Spring Meeting, Warwick, UK (MH) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited speaker at annual spring meeting of the Genetics Society and British Society for Developmental Biology (BSDB) in Warwick, UK (2017)
Year(s) Of Engagement Activity 2017
 
Description Genetics Society annual autumn meeting - poster presentation RS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presentation of a poster with the newest data on this work. Meeting held in London, UK (2017).
Year(s) Of Engagement Activity 2017
 
Description Genetics Society annual autumn meeting - poster presentation RS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Poster presentation by postdoc RS at above conference, interaction with other experts in the field, new ideas for research directions developed
Year(s) Of Engagement Activity 2016
 
Description How big data is changing science 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Interview with Tom Chivers on "How big data is changing science" (https://mosaicscience.com/story/how-big-data-changing-science-algorithms-research-genomics/)
Year(s) Of Engagement Activity 2018
 
Description IFPA Meeting, Manchester, UK (MH) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited talk at IFPA Meeting held in Manchester, UK (2017)
Year(s) Of Engagement Activity 2017
 
Description ISSHP Meeting, Berlin, Germany (MH) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited talk at ISSHP Meeting held in Berlin, Germany (2017)
Year(s) Of Engagement Activity 2017
 
Description InsideSTEM Initiative 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Two teachers visited the Babraham Institute as part of the InsideSTEM initiative in October 2018; I hosted the teachers for one day. I explained the ongoing research efforts in my lab, and we discussed possible ways to incorporate aspects of the research undertaken at the Babraham Institute into their curriculum.
Year(s) Of Engagement Activity 2018
 
Description Keynote speaker, CTR Anniversary Meeting, Cambridge, UK (MH) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Keynote lecture at 10th Anniversary Meeting of the Centre for Trophoblast Research, University of Cambridge (2017)
Year(s) Of Engagement Activity 2017
 
Description London International Youth Science Forum 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact Around 40 international pupils visited the Babraham Institute as part of the programme during the London International Youth Science Forum (LIYSF), for which they had been selected. I gave a presentation on pluripotent stem cells and genome organisation, and a tour for the pupils around the institute.
Year(s) Of Engagement Activity 2018
 
Description Meeting organiser, Reproduction and Development, Cambridge 2018 (MH) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Co-organisation of meeting, Reproduction and Development, held in Cambridge, UK (2018).
Year(s) Of Engagement Activity 2018
 
Description NIB conference poster presentation (RS) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Participation including poster presentation at National Institutes of Bioscience (NIB) conference 2015. Engagement with other BBSRC institutes' scientists and research focus.
Year(s) Of Engagement Activity 2015
 
Description Nine invited presentations at international meetings, including EMBO, FASEB, Keystone, American Association for Cancer Research 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Conference presentations about our research
Year(s) Of Engagement Activity 2018
 
Description Organisation of C.elegans Cambridge local area meetings 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact An audience of about 10-15 science labs from around the Cambridge area attend these events, including many PhD students and postdocs. The aim of these meetings is dissemination of techniques and science as well as networking.
Year(s) Of Engagement Activity 2015,2017,2018
 
Description Partcipation in The Future of Ageing 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact A representative of the Casanueva lab attended a debate on the future of gein at London School of Economics geared towards general public.
Year(s) Of Engagement Activity 2018
 
Description Podcast with Dr Kat Arney on the impact of placentation and maternal age on reproductive outcome 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Podcast as descibed above
Year(s) Of Engagement Activity 2017
 
Description Postgraduate course Epigenetics in Reproductive Biology, University of Murcia, Spain (VPG) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Invited talk and workshop participation as part of postgraduate course on reproductive epigenetics
Year(s) Of Engagement Activity 2016,2017
 
Description Presentation to the EMBL-EBI Industry program 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Presentation to the EMBL-EBI Industry program, representing pharma and agri-food industry, on the use of genome scale metabolic models for personalised medicine.
Year(s) Of Engagement Activity 2018
 
Description Radio interview DeutschlandFunk 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Radio Interview for DeutschlandFunk on the impact of maternal age on pregnancy success, irrespective of the increased risk of defects in the egg
Year(s) Of Engagement Activity 2017
URL http://www.deutschlandfunk.de/alter-des-uterus-entscheidend-junges-glueck-in-jungen.676.de.html?dram...
 
Description Royal Society Partnering Award - CS + LW, NM, SC 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Successful application for Royal Society Partnering Award. Poster 6 selected 6th form students over the course of 1 week and conducted in-depth research project. Data analysis followed at the pupils' school directly.
Year(s) Of Engagement Activity 2016,2017
 
Description Royal Society Summer Exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Babraham Institute exhibit on the Epigenetic Ageing Clock as invited entry presented at the Royal Society Summer Exhibition, involving activities and question/answer interactions with members of the public, fellows of the Royal Society, policymakers
Year(s) Of Engagement Activity 2018
 
Description Savile Club epigenetics talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Presentation about epigenetics at the London Savile Club
Year(s) Of Engagement Activity 2018
 
Description Schools Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Groups of 5-6 6th-form students take part in a one-day visit to 2 research groups at the Babraham Institute and conduct two small research experiments during that day.
Year(s) Of Engagement Activity 2017,2018
 
Description Schools Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Project design, scientific background induction and practical supervision for 6th form students as well as teachers during Annual Schools Day.
Year(s) Of Engagement Activity 2015,2016,2017
 
Description Schools Day 2018 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Around 200 pupils attended for our annual School's Day, of which 10 participated in the activities organised by my group. We talked with pupils about genes, gene mutations, regulatory elements, cellular differentiation and lineage specification, stem cells, and three-dimensional genome organisation. For the practical part, the students performed a fluorescent in situ hybridisation (FISH) experiment to determine the nuclear localisation of an enhancer relative to its target gene in the three-dimensional space of the nucleus.
Year(s) Of Engagement Activity 2018
 
Description Schools Day 2019 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Around 250 pupils attended for our annual School's Day, of which 9 participated in the activities organised by my group. We talked with pupils about genes, gene mutations, regulatory elements, cellular differentiation and lineage specification, stem cells, and three-dimensional genome organisation. For the practical part, the students performed a fluorescent in situ hybridisation (FISH) experiment to determine the nuclear localisation of an enhancer relative to its target gene in the three-dimensional space of the nucleus.
Year(s) Of Engagement Activity 2019
 
Description Sophianum School collaboration - Technasium 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact The Babraham Institute is continuing to coordinate activities supporting its commitment as a signatory of the Concordat on Openness on Animal Research. Institute staff, including animal unit managers, have been working closely with a school in the Netherlands to prepare and launch the Institute's contribution to the national 'Technasium' education programme, which aims to draw together students and industry.

Two projects, developed in collaboration with the Institute's Public Engagement team and teachers from the Sophianum School in Gulpen, will challenge students to research and design systems to improve the efficiency and safety of animal care systems. A third project will require the students to research how legislation regulating the use of animals in science, as well as public opinion, can vary throughout Europe and the world.

A two-day visit on 19th & 20th May will kick-start a 10-week programme for the 15-year old students, who will work in teams and compete to design the best solutions to the challenges. The Institute's animal technicians will monitor student progress by commenting on YouTube videos posted fortnightly by the teams. Regular video calls into the animal unit and the Institute's laboratories will allow live discussion between the students, the animal technicians and the scientists who use animals as part of their research.

The challenge projects will finish in July, with the winning Sophianum team coming to the Babraham Institute as part of their prize. The students will visit Institute animal facilities and will get a chance to see the award-winning camera system which displays live feeds from the facility - allowing groups to appreciate first-hand both the animal care environment and the nature of working within an animal research unit.

This pilot project will also involve sixth-form students at the school who will learn about the Institute's research and take part in workshops to discuss the ethics of the use of animals in science. The Institute has been running ethics workshops for secondary and sixth form students since 2005, with contributions from Understanding Animal Research, the European Animal Research Association and the Institute of Animal Technology.

The success of the Technasium project will be evaluated by both the Institute and Sophianum School, with a view to developing future challenges.
Year(s) Of Engagement Activity 2017,2018
 
Description SysMod 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I organised the 2nd meeting of the ISCB Community of Special Interest SysMod. Up to 270 people attended depending on the talk.
Year(s) Of Engagement Activity 2017
 
Description Talk at Cambourne Library 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact 15 general audience attended an Epigenetics presentation and discussion
Year(s) Of Engagement Activity 2018
 
Description The Ageing Cell Conference, Cambridge, UK (MH) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited talk at The Ageing Cell Conference held in Cambridge, UK (2017)
Year(s) Of Engagement Activity 2017
 
Description Twilight teacher training event, Bioscience lite-CRISPR-Cas9 genome editing- technology, applications and implication, Cambridge (UK) (VPG) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Talk and Q&A session with high school teachers to update and inform them on state-of-the-art genome editing tools
Year(s) Of Engagement Activity 2017
 
Description UKRI launch 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact UKRI launch event 2018
Year(s) Of Engagement Activity 2018
 
Description WT/EBI course in silico systems biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I organised this one-week course, and gave presentations entitled: "What is Systems Biology? Where does it come from?", "The many faces of modelling in biology", "Modelling in systems biology, a few challenges", "From art to engineering: two decades of standards and tools towards digital organisms", "Modelling chemical kinetics" plus a tutorial on stochastic simulations of biological systems.
Year(s) Of Engagement Activity 2017
 
Description Wellcome Genome Campus Cell Fate Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact This was an invitation only workshop organised by us on the Hinxton campus which brought together some of the international leaders working on cell fate biology and pathology.
A meeting report was produced subsequently.
Year(s) Of Engagement Activity 2018
 
Description eLife Community Webinar - Refreshing approaches to researcher evaluation 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I animated a webinar discussing various ways to bypass the traditional publication-based evaluation of researchers.
Year(s) Of Engagement Activity 2017