Non-coding RNAs and transcription as epigenetic regulators

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

Transcription and ncRNAs are major modifiers of the epigenetic state, but the mechanisms by which they act are still poorly understood. In this Theme, we investigate the role of ncRNAs, initially using a yeast model system, (1) in genome stability, (2) their influence on meiotic recombination, (3) the role of antisense ncRNAs in chromatin structure modulation, and in mice (4) how transcription promotes DNA methylation at imprinted loci.

Publications

10 25 50
 
Description Transcription and non-coding RNAs are major modifiers of the epigenetic state, but the mechanisms by which they act are still poorly understood. In the oocyte system, we showed how gene transcription confers different layers of epigenetic marks by remodelling histones to direct DNA methylation. We have subsequently been able to show that transcriptional differences, for example that relate to how oocytes are sourced for assisted reproduction technologies, are associated with predictable differences in DNA methylation.In yeast, we characterised the interplay between transcription and genetic change, showing that cells are able to remodel specific regions of their genomes in response to environmental conditions, based on the transcriptional changes induced by those environments. We further elucidated the manner in which genetic changes, particularly in DNA copy number, influence RNA processing, showing that complex feedback relationships exist between the genome and the transcriptome. These findings have underpinned more work in the following Epigenetics ISP characterising the changes in the genome and epigenome that occur during ageing in yeast and how these impact the ageing process.
Exploitation Route This is all covered in other entries
Sectors 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.
First Year Of Impact 2014
Sector Healthcare
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 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 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 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 Senior Research Fellowship
Amount £1,426,775 (GBP)
Funding ID 110216/Z/15/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2016 
End 03/2021
 
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 Yeast gene expression in meiosis 
Description Gene expression in meiosis of wt and trf4 mutant yeast 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact data re-use 
URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60221
 
Description Analysis of histone modifications in mice with loss-of-imprinting of Zac1 
Organisation Clermont Université
Country France 
Sector Academic/University 
PI Contribution Our group was responsible for framing the project and experimental design; we provided tissues from mice with loss-of-imprinting of Zac1.
Collaborator Contribution Their group performed ChIP-PCR analysis in tissues from Zac1 loss-of-imprinting mice we provided.
Impact Joint publication Veselovska et al. 2015 Genome Biol.
Start Year 2013
 
Description Antisense-mediated promoter silencing in imprinted locus Gnas 
Organisation MRC Harwell
Department MRC Mammalian Genetics Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution Our team provided a gene targeting construct for one of the targeting alleles used by the partner, which complemented work we previously published in Chotalia et al. 2009 Genes & Dev.
Collaborator Contribution Their team was responsible for framing the project and experimental design and data analysis.
Impact Joint publications Williamson et al. PLoS Genet. 2011; Tibbit et al., 2015 Non-coding RNA
Start Year 2007
 
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 MR for CJ paper 
Organisation University of Cambridge
Department Cambridge Systems Biology Centre (CSBC)
Country United Kingdom 
Sector Academic/University 
PI Contribution We performed mechanistic analysis of rDNA CNV
Collaborator Contribution Markus Ralser's group performed metabolomics analysis
Impact Jack et al PNAS paper
Start Year 2013
 
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
 
Title AGENT TO PREVENT THE EMERGENCE OF RESISTANCE TO A THERAPEUTIC AGENT 
Description The invention relates to the use of a histone acetyltransferase inhibitor to prevent the emergence of mutations causing resistance to a therapeutic agent. The invention also relates to the use of an mTOR inhibitor to prevent the emergence of mutations causing resistance to a therapeutic agent. The invention also relates to novel pharmaceutical compositions comprising a histone acetyltransferase inhibitor or an mTOR inhibitor in combination with a therapeutic agent and to the uses of said compositions in the treatment of disease, such as cancer. 
IP Reference WO2017085473 
Protection Patent application published
Year Protection Granted 2017
Licensed No
Impact Used to leverage contacts with biotech industry, notably within Astra Zeneca.
 
Description Article on JH lab Ageing Research in Cambridge Independent 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact An article on our yeast research was published following an in depth interview with me (JH).
Year(s) Of Engagement Activity 2017
 
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 Poster at Ageing meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact General interest in presented work.

networking
Year(s) Of Engagement Activity 2014
 
Description Poster at EMBO transcription meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact General interest in presented work.

Presentation by my student, he successfully approached future employers.
Year(s) Of Engagement Activity 2014
 
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 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 (annual) 
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 Visit by school children to do experiments in BI labs. All BI labs participate.
Year(s) Of Engagement Activity 2010,2011,2012,2013,2014,2015,2016
 
Description Talk and poster at EMBO Evolution meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact General interest in presented work.

networking
Year(s) Of Engagement Activity 2014
 
Description Talk at DNA Replication as a Source of DNA Damage Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk to other members of research community.
Year(s) Of Engagement Activity 2017
URL https://www.fusion-conferences.com/conference67.php
 
Description Talk at EMBO non-coding RNA meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact General interest in presented work.

networking
Year(s) Of Engagement Activity 2014
 
Description Talk at Epigenesys meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation at Epigenesys meeting
Year(s) Of Engagement Activity 2016
 
Description Talk at UK RNA meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Conference presentation
Year(s) Of Engagement Activity 2016
 
Description Talk at UK Yeast meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact General interest in presented work, invitations for further talks.

networking
Year(s) Of Engagement Activity 2012
 
Description Talk at University of Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar and conference presentation

networking
Year(s) Of Engagement Activity 2013
 
Description Talk at University of Manchester 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Invited Seminar at Faculty of Biology

Networking
Year(s) Of Engagement Activity 2013