Developmental dynamics of the epigenome
Lead Research Organisation:
Babraham Institute
Department Name: UNLISTED
Abstract
This Theme examines in detail the mechanisms and genome-wide dynamics of reprogramming and programming events in GCs and early embryos, in tissues during ageing as well as the biology involved. It builds directly upon the resource established in Theme 1, and adds value to it. It also involves analysis of additional epigenomes, e.g. in conditional knockouts or transgenics of epigeetic modifiers. The objectives are to determine the mechanistic basis of: (1) epigenetic reprogramming in PGCs, (2) programng in later stage GCs, (3) reprogramming in early embryos (4), programming during early lineage commitment to ICM, TE, and PE, and derived stem cells (5), imprinting and transgenerational inheritance (6,) Influence of ageing upon the epigenome of the non-replicating genome of cardiac myocytes and effects thereof upon cardiac adaptation.
Organisations
- Babraham Institute, United Kingdom (Lead Research Organisation)
- University of Edinburgh, United Kingdom (Collaboration)
- Stuttgart University, Germany (Collaboration)
- Karolinska Institute, Sweden (Collaboration)
- University of Bonn, Germany (Collaboration)
- Merck (Collaboration)
- University of Texas at San Antonio, United States (Collaboration)
- Broad Institute (Collaboration)
- Medical Research Council (Collaboration)
- Active Motif (Collaboration)
- Technical University Dresden, Germany (Collaboration)
- Yokohama City University (Collaboration)
- Queen Mary, University of London, United Kingdom (Collaboration)
- University of Toronto (Collaboration)
- University of Cambridge (Collaboration)
- National Institute of Environmental Health Sciences (Collaboration)
- Cancer Research Technology (CRT) (Collaboration)
- Helmholtz Zentrum München (Collaboration)
- RIKEN, Japan (Collaboration)
- EMBL - European Bioinformatics Institute, United Kingdom (Collaboration)
- Cambridge Epigenetix (Collaboration)
Publications
Angermueller C
(2017)
DeepCpG: accurate prediction of single-cell DNA methylation states using deep learning.
in Genome biology
Arand J
(2015)
Selective impairment of methylation maintenance is the major cause of DNA methylation reprogramming in the early embryo.
in Epigenetics & chromatin
Berrens RV
(2015)
Prmt5: a guardian of the germline protects future generations.
in The EMBO journal
Berrens RV
(2017)
An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells.
in Cell stem cell
Branco MR
(2016)
Maternal DNA Methylation Regulates Early Trophoblast Development.
in Developmental cell
Cambuli F
(2014)
Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast.
in Nature communications
Chandra T
(2015)
Global reorganization of the nuclear landscape in senescent cells.
in Cell reports
Chrysanthou S
(2018)
A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells.
in Stem cell reports
Collier AJ
(2017)
Comprehensive Cell Surface Protein Profiling Identifies Specific Markers of Human Naive and Primed Pluripotent States.
in Cell stem cell
De La Rica L
(2016)
TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells.
in Genome biology
| Title | ARTE Epigenetics television programme |
| Description | This is a film on research activities of several european epigenetics labs |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2015 |
| Impact | Popular on YouTube |
| Description | Reprogramming of epigenetic information is vital to allow changes in cell potency during major development transitions, but also to mitigate against the possibility of transmission of undesirable acquired epigenetic changes between generations. However, the mechanisms responsible for epigenetic reprogramming were largely unknown. We have elucidated mechanisms by which cytosine methylation is actively removed from the parental genomes very soon after fertilisation. We have also identified that dampening DNA methylation maintenance activity is the major cause of reprogramming in fetal germ cells and, using culture models, we show that similar principles apply in human cells as well as in mouse. We have discovered that global hypomethylation is an invariant hallmark of naive pluripotency in mice and humans. Our detailed studies of epigenetic change during growth and development has allowed us to develop exciting novel model systems and make new discoveries about the ageing process. For example, we have characterised the mouse epigenetic clock, the importance of placental function in age-linked pregnancy complications, the epigenetic mechanisms differentiating normal and pathological cardiac hypertrophy, the nuclear architecture of senescent cells and the effects of dietary change on health-span in mice and yeast. These studies have formed the basis of the work being proposed in the current epigenetics ISP. |
| Exploitation Route | These findings have been taken up by the community as judged by research publications that build on our results. |
| Sectors | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
| URL | https://www.babraham.ac.uk/our-research/epigenetics |
| Description | As part of the wider Babraham Institute strategy, across the course of this ISP we have developed a much broader public engagement strategy, undertaking large prestigious events including two Royal Society exhibits specifically showcasing our work (Epigenetics: DNA is not your destiny and Race Against the Ageing Clock), as well as presentations at local science fairs and engagement with local schools. We have also contributed substantially to transferable skills development, analytical thinking and training, mentoring and career development. We have also significantly contributed to KEC activities eg helping to spin out the company Cambridge Epigenetix and continuing membership on their SAB. |
| First Year Of Impact | 2013 |
| Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal,Economic |
| Description | Babraham Institute Public Dialogue 2015 |
| Geographic Reach | National |
| Policy Influence Type | Citation in other policy documents |
| Impact | Improved public understanding of biological sciences and the work of the Babraham Institute |
| URL | http://www.babraham.ac.uk/get-involved/partnerships-page/public-dialogue |
| 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 SAB Development and Genetics Unit Institut Curie |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Participation in a advisory committee |
| Impact | Probably the best unit of this type in France |
| 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 | European Research Council committee member |
| Geographic Reach | Europe |
| Policy Influence Type | Participation in a advisory committee |
| Description | Gene editing policy |
| Geographic Reach | National |
| Policy Influence Type | Participation in a advisory committee |
| 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 | Research Advisory Board, Wellbeing of Women |
| Geographic Reach | National |
| Policy Influence Type | Participation in advisory committee |
| Impact | I served as member of the scientific advisory committee to the charity Wellbeing of Women, which reviews and makes decisions on grant funding in the general field of reproductive medicine. Some of the work funded through WoW has led to improvements in health care, novel diagnostic methods, etc. |
| 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 | EU BLUEPRINT |
| Amount | £500,000 (GBP) |
| Funding ID | 282510 |
| Organisation | European Commission |
| Department | Seventh Framework Programme (FP7) |
| Sector | Public |
| Country | European Union (EU) |
| Start | |
| Description | EU NoE EpiGeneSys |
| Amount | £400,000 (GBP) |
| Funding ID | 257082 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | |
| Description | MRC Collaboration Grant (deep sequencing in Epigenomics) |
| Amount | £960,000 (GBP) |
| Funding ID | G0801156 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | MRC iCASE training award |
| Amount | £111,236 (GBP) |
| Funding ID | MR/M017427/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2016 |
| End | 09/2020 |
| Description | Next Generation Fellowship for postdoctoral researcher Dr Paulina Latos |
| Amount | £167,000 (GBP) |
| Organisation | University of Cambridge |
| Department | Centre for Trophoblast Research |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 09/2013 |
| End | 08/2016 |
| Description | Wellcome Trust Strategic Award |
| Amount | £2,400,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2015 |
| End | 12/2019 |
| Description | Wellcome Trust Strategic Award |
| Amount | £254,000 (GBP) |
| Funding ID | WT100160MA |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2013 |
| End | 03/2018 |
| Title | Single cell triple-omics |
| Description | Single cell triple-omics combining transcriptome, methylome, and chromatin accessibility from the same single cell. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | This method was just published. |
| Title | iTSCs |
| Description | Novel method that allows for the generation of trophoblast stem cells (TSCs) from fibroblasts to study development and differentiation of the placenta lineage. |
| Type Of Material | Cell line |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | This method makes the establishment of TSCs tremendously easier, and does not require the isolation of multiple rounds of blastocysts from time-mated females (mice). This in turn reduced the number of required animals. |
| 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 | Chromatin modifications during mouse oogenesis |
| Description | High quality native ChIP-seq datasets for histone modifications H3K4me3, H3K27ac, H3K27me3 during oocyte growth and fully grown oocytes in the mouse. ChIP-seq datasets for H3K4me3 in oocytes genetically deficient in DNA methylation (Dnmt3a/Dnmt3b nulls). ChIP-seq datasets for oocytes genetically deficient in the major H3K4 methyltransferase MLL2 (KMT2B). Published in Hanna et al. Nat. Struct. Mol. Biol. 2018 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | Recently released datasets, too early to identify impact outside of research group. |
| URL | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE93941GSE93941 |
| Title | DMDD |
| Description | As part of the Wellcome Trust funded Strategic Award "Deciphering the Mechanisms of Developmental Diseases", we have generated a database in which we collect phenoytping data of the mouse placenta at various gestational stages. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | Broad survey of embryonic lethal gene mutations for defects in embryonic and placental development. Efforts will lead, for the first time, to a global overview of the number and identity of genes, and the molecular pathways they regulate, involved in the development of the placenta as an essential organ ensuring reproductive success and health of the baby. |
| URL | http://www.nimr.mrc.ac.uk/news/deciphering-the-mechanisms-of-developmental-disorders-progress-report... |
| Title | DNA methylation in Hira oocytes |
| Description | Genome-wide, single-cell DNA methylation data from mouse oocytes lacking the histone chaperone HIRA, and associated controls, as reported in Nashun et al. 2015 Molecular Cell 60, 611-625. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | Too soon to define notable impacts, as the accompanying paper, Nashun et al. 2015 Molecular Cell, was published in October 2015. |
| URL | http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66629 |
| Title | DNA methylation in oocytes deficient in histone modifier |
| Description | Genome-wide DNA methylation datasets (PBAT) and single-cell RNA-seq datasets from oocytes genetically deficient in the H3K4me3 methyltransferase MLL2 (KMT2B). Published in Hanna et al. 2018 Nat. Struct. Mol. Biol. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | Recently released, too early to identify impact outside of research group. |
| URL | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE93941GSE93941 |
| Title | Epigenomic analysis of mouse post-implantation embryos |
| Description | Allellic DNA methylation, gene expression and histone modification datasets from embryonic tissues from mouse. Allows genome-wide identification of genes controlled by genomic imprinting, and distinction of imprinting conferred by DNA methylation or repressive chromatin in oocytes. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | Published in Hanna et al. Genome Biol 2019 PMID: 31665063 |
| URL | http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE124216 |
| Title | Oocyte ChIP-seq datasets |
| Description | ChIP-seq datasets for selected histone modifications in mouse growing oocytes. DNA methylation profiles of oocytes lacking the histone demethylases KDM1A, KDM1B. As reported in Stewart et al., 2015 Genes and Development, 29, 2449-2462 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | Too soon to define notable impacts, as the associated manuscript was published in Genes and Development in December 2015 |
| URL | http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74549 |
| 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 | 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 |
| 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 | Analysis of Mll2-deficient oocytes |
| Organisation | Technical University of Dresden |
| Department | Biotechnology Center |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | We framed the biological question and were responsible for experimental design and data analysis. We performed DNA methylation and histone modification analysis of oocytes conditionally deleted for Mll2 provided by the partner. |
| Collaborator Contribution | Provided mice with conditional knock-out allele of Mll2 and Mll2-deficient oocytes. |
| Impact | Joint publication: Hanna et al., Nat. Struct. Mol. Biol. 2018. Deposited sequence datasets at NCBI GEO: GSE93941. |
| Start Year | 2013 |
| Description | Analysis of Setd1b-deficient oocytes |
| Organisation | Technical University of Dresden |
| Department | Biotechnology Center |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | We performed analysis of RNA-seq datasets in oocytes conditionally deleted for Setd1b generated by the partner, with reference to our mouse oocyte transcriptome assemblies (Veselovska et al., 2015 Genome Biol; Gahurova et al., 2017 Epigenetics & Chromatin). |
| Collaborator Contribution | Partner was responsible for framing the project and experimental design and providing data from mice with conditional knock-out allele of Setd1b in oocytes |
| Impact | Joint publication: Brici et al., Development 2017 |
| Start Year | 2013 |
| Description | Austin Smith |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Epigenomics and multi-omics sequencing |
| Collaborator Contribution | Human and mouse pluripotent stem cells |
| Impact | Several collaborative publications. |
| Start Year | 2013 |
| Description | Bioinformatic analysis of oocyte ChIP-seq data |
| Organisation | Helmholtz Zentrum München |
| Department | Institute of Computational Biology |
| Country | Germany |
| Sector | Private |
| PI Contribution | We provided ChIP-seq datasets for various histone modifications in mouse wild-type and genetic knock-out oocytes to enable partner to test new informatics tools they had developed. |
| Collaborator Contribution | The partner provided new informatics methods, based on multivariate Hidden-Markov Models, to enable analysis of multiple ChIP-seq datasets, with focus on multivariate comparisons. |
| Impact | Joint publication: Hanna et al., Nat. Struct. Mol. Biol. 2018. Deposited sequence datasets at NCBI GEO: GSE93941. Hosted visiting bioinformatics PhD student from collaborating lab. Inter-disciplinarity: partner provides modelling and informatics expertise, our group provides biological datasets. |
| Start Year | 2016 |
| Description | Bioinformatics analysis of ChIP-seq and RNA-seq data |
| Organisation | EMBL European Bioinformatics Institute (EMBL - EBI) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Provided extensive high-throughput sequencing datasets for analysis. |
| Collaborator Contribution | Expert analysis of ChIP-seq data and data mining of existing datasets |
| Impact | Multi-discipliniary, involving mathematical biology and bioinformatics. Joint manuscript submitted October 2014 |
| Start Year | 2014 |
| Description | Bioinformatics analysis of ChIP-seq and RNA-seq data |
| Organisation | University of Toronto |
| Country | Canada |
| Sector | Academic/University |
| PI Contribution | Provided large-scala datasets for analysis. |
| Collaborator Contribution | Analysed the data. |
| Impact | Latos P.A., Sienerth A.R., Murray A., Senner C.E., Muto M., Ikawa M., Oxley D., Burge S., Cox B. and Hemberger M. (2015). Elf5-centered transcription factor hub controls trophoblast stem cell self-renewal and differentiation through stoichiometry-sensitive shifts in target gene networks. Genes & Development, 29: 2435-2448. |
| Start Year | 2014 |
| Description | CEGX |
| Organisation | Cambridge Epigenetix |
| Country | United Kingdom |
| Sector | Private |
| 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 | Consultancy Cambridge Epigenetix |
| Organisation | Cambridge Epigenetix |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | I am a consultant for the company |
| Collaborator Contribution | None at present |
| Impact | Oxidative bisulfite sequencing |
| Start Year | 2012 |
| Description | DNA methylation analysis in oocytes genetically deficient for Kdm1a (Lsd1) and Kdm1b (Aof1) |
| Organisation | University of Texas |
| Department | M. D. Anderson Cancer Center |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We were responsible for framing the project and experimental design and performed genome-wide DNA methylation analysis in oocytes genetically deficient in the H3K4me2 demethylases KDM1A or KDM1B, provided by the collaborating group. |
| Collaborator Contribution | The partner provided oocytes from mice genetically deficient in Kdm1a or Kdm1b; provided RNA-seq datasets for these oocytes. |
| Impact | Joint publications Stewart et al., 2015 Genes & Dev; Gahurova et al. 2017 Epigenetics & Chromatin. Deposited sequence datasets at NCBI GEO: GSE73803 and GSE74549. |
| Start Year | 2011 |
| Description | DNA methylation analysis in oocytes genetically deficient in Hira |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Clinical Sciences Centre (CSC) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | We performed single-cell, genome-wide bisulphite sequencing of oocytes deficient in H3.3 chaperone HIRA, provided by the collaborating group; using our newly established single-cell BS-seq method (Smallwood et al., 2014 Nat. Meths). |
| Collaborator Contribution | The partner was responsible for framing the project and experimental design and provided mouse oocytes conditionally deleted in Hira. |
| Impact | Joint publication Nashun et al. 2015 Mol. Cell. Deposited sequence datasets at NCBI GSE66629. |
| Start Year | 2014 |
| 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 | Donal O'Carrol |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Helped with methylome sequencing and computational work. |
| Collaborator Contribution | Conceived and conducted the study. |
| Impact | Publication Vasiliauskaite et al 2017. Developmental biologists, epigeneticists, computational biologists. |
| Start Year | 2016 |
| Description | Gastrulation team |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Conceived of the project and lead partner. Contributing single cell multi-omics and embryology. |
| Collaborator Contribution | Helped to conceive of the project and several experimental and computational contributions. |
| Impact | First publication Mohammed et al 2017. Experimental embryology, single cell biology, computation, modelling, epigenetics. |
| Start Year | 2014 |
| Description | Human Cell Atlas |
| Organisation | Broad Institute |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | Contributed to formulating the white paper of the Human Cell Atlas. |
| Collaborator Contribution | Conceived the project and brought the international consortium together. |
| Impact | The white paper was published Regev et al 2017. It involves single cell biologists and computational and modelling scientists. |
| Start Year | 2016 |
| Description | Jenny Nichols mouse and human embryology |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Single cell multi-omics, mutants of epigenetic regulators. |
| Collaborator Contribution | Mouse and human embryos |
| Impact | Several collaborative publications and two joint grants. Multi-disciplinary between epigenetics, multi-omics, embryology, stem cell research. |
| Start Year | 2014 |
| Description | Jenny Nichols, Austin Smith |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Contributed to conceiving studies. Epigenetic profiling and analysis. |
| Collaborator Contribution | Conceived and conducted studies. |
| Impact | Publications Kalkan et al 2017, Guo et al 2017. Involves embryologists, stem cell biologists, computational biologists, epigeneticists. |
| Start Year | 2016 |
| Description | Jurkowski |
| Organisation | University of Stuttgart |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Helped with reagents and interpretation. |
| Collaborator Contribution | Conceived and conducted study. |
| Impact | Publication Stepper et al 2017. Involves biochemists, epigeneticists. |
| Start Year | 2016 |
| Description | MRC EASIH |
| Organisation | University of Cambridge |
| Department | Cambridge Institute for Medical Research (CIMR) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | increased opportunities for deep sequencing using alternative platforms such as Roche 454 and ABI Solid |
| Collaborator Contribution | MRC East Anglia Sequencing and Informatics Hub established in 2009 |
| Impact | see above |
| Start Year | 2009 |
| Description | Miguel Branco for TET paper |
| Organisation | Queen Mary University of London |
| Department | Blizard Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | RNA analysis of L1 trasposon |
| Collaborator Contribution | This project was run by the Branco lab, they produced the bulk of the data and published the paper. |
| Impact | Research publication PMID 27863519 |
| Start Year | 2015 |
| Description | Millipore DNA modification antibodies |
| Organisation | Merck |
| Department | MilliporeSigma |
| 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 | DNA modification antibodies |
| Start Year | 2011 |
| Description | Reprogramming of MEFs towards iTSCs and establishment of defined TSC culture conditions |
| Organisation | University of Bonn |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Genome-wide DNA methylation analysis of various clones and reprogrammed cells. Bioinformatic analysis of these data. Figures for manuscripts. |
| Collaborator Contribution | Provided DNA for the above analysis. Performed other experiments to bring this project to conclusion. |
| Impact | Kubaczka C., Senner C.E., Araúzo-Bravo M.J., Sharma N., Kuckenberg P., Becker A., Zimmer A., Brüstle O., Peitz M., Hemberger M. and Schorle H. (2014). Derivation and maintenance of murine trophoblast stem cells under defined conditions. Stem Cell Reports, 2: 232-242. Kubaczka C., Senner C.E., Cierlitza M., Araúzo-Bravo M.J., Kuckenberg P., Peitz M., Hemberger M. and Schorle H. (2015). Direct induction of trophoblast stem cells from murine fibroblasts. Cell Stem Cells, 17: 557-568. |
| Start Year | 2012 |
| Description | Role of Np95 in epigenetic reprogramming |
| Organisation | RIKEN |
| Country | Japan |
| Sector | Public |
| PI Contribution | We are analysing the effects of Np95 deletion in zygotes and early embryos |
| Collaborator Contribution | Contribution of unpublished conditional knockout in the key epigenetic regulator Np95 |
| Impact | The first results have been obtained and look quite interesting |
| Start Year | 2008 |
| Description | Single-cell epigenomic profiling of spermatogonial stem cells |
| Organisation | Yokohama City University |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Our group is providing expertise in single-cell methylation and expression profiling methods. |
| Collaborator Contribution | Their group is responsible for framing the project and experimental design and for providing isolated mouse spermatogonial stem cells. |
| Impact | Hosted visit by post-doc from collaborating group to initiate single cell methylation/transcription profiling. Joint grant awarded: Royal Society International Exchange Award IEC\R3\170052 (March 2018 March 2020): Analysis of spermatogonial stem cell maintenance and differentiation system by the state-of-the-art single-cell technology. |
| Start Year | 2016 |
| 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 |
| Title | Novel Method |
| Description | A novel method to manipulate potency of pluripotent cells |
| IP Reference | US20160186207 |
| Protection | Patent application published |
| Year Protection Granted | 2015 |
| Licensed | Commercial In Confidence |
| Impact | In progress |
| Description | Babraham 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 | As part of the annual Babraham Schools' Day, my group hosted 5 GCSE and 5 A level students for half-day practical sessions in the lab. |
| Year(s) Of Engagement Activity | 2017 |
| 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 | 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 | 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 | 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 | 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 | Member, Board of Managers at Centre for Trophoblast Research |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Supporters |
| Results and Impact | As member of the Board of Managers at the CTR in Cambridge we make decisions on the award of PhD scholarships, postdoctoral fellowships and direct the general focal points of local research activity in the field of placental biology. PhD students admitted to the University of Cambridge; postdoctoral researchers' career path enhanced |
| Year(s) Of Engagement Activity | 2013,2014,2015,2016 |
| 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 | Press release - Keeping eggs fresh with epigenetics |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Press release from Babraham to accompany publication of paper 'MLL2 conveys transcription-independent H3K4me3 in the oocyte', by Hanna et al. Nat. Struct. Mol. Biol. 2018. Picked up by 9 news outlets and blogs. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.babraham.ac.uk/news/2018/01/keeping-egg-cells-fresh-with-epigenetics |
| 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 | STEM teacher visit |
| 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 | As part of a week-long visit to the Institute, my group hosted 3 biology A-level teachers from local schools for involvement in practical work in the lab over a 2-day period. |
| Year(s) Of Engagement Activity | 2016 |
| Description | School's Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | provided basic explanation of early development and the importance of the placenta for growth of a baby; hands-on experience for students in staining and microscopic analysis of a mouse placenta rose awareness of research activities and importance of basic research to understand common pregnancy-associated diseases |
| Year(s) Of Engagement Activity | 2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016 |
| 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 |
| 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 | 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 |