Epigenetics and Development

Lead Research Organisation: MRC Human Genetics Unit

Abstract

Our DNA encodes the central core of genetic information of the cell, which is dictated by the order of the four bases: adenine, cytosine, guanine and thymine. Throughout development, there are distinct patterns of gene expression at different stages and cell types. Consequently, there must be a level of information apart from the primary DNA sequence that specifies the selective use of genetic information in different cells. A modified base, 5-methylcytosine (5mC), is found on DNA that exhibits distinct patterns between different cells. The presence of 5mC at genes can result in gene silencing.||We are trying to understand the mechanisms by which the enzymes that introduce methylation onto DNA cause gene silencing during animal development and why the modified base, 5mC, is necessary for cellular stability? The importance of 5mC is underlined by the observation that many cancers and rare human diseases have altered patterns of DNA methylation compared to normal cells.||To understand the role of DNA methylating enzymes in cells, we produce cells lacking these enzymes and characterise what happens at the molecular level. In this way, we hope to understand the role of this important process in development and disease.

Technical Summary

Epigenetics describes the variation of gene expression that is not due to changes in the DNA sequence. It is an important process during animal early development for setting up and maintaining stable patterns of gene transcription in adult tissues. In essence it describes how modification of chromatin or DNA regulates a genes activity.||Our main interest is determining the interplay between chromatin and DNA based silencing mechanisms in maintaining gene silencing during early animal development? We have made some exciting discoveries establishing the importance of epigenetic regulators in determining the onset of transcription during early development in amphibians, and how mis-regulation of these processes may lead to apoptosis and subsequent alterations in cellular identity and development.||The maintenance cytosine methyltransferase, xDnmt1, is responsible for maintaining high levels of DNA methylation in development. We have shown that it also acts as a direct transcription repressor protein, independently of its catalytic function, in early embryos. In addition we have identified a potential pathway though which loss of xDnmt1 function results in direct activation of a cell death pathway.||We believe our findings have important implications for the molecular basis of diverse human diseases in which epigenetic regulation is altered and potentially an understanding of the nature of cellular potency (stem cells). Our work may also contribute to the development of safe health care applications such as small molecule inhibitors of Dnmt1 function.

Publications

10 25 50
 
Description Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT)
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL http://cot.food.gov.uk/cotstatements/cotstatementsyrs/cotstatements2008/cot200803
 
Description Danish Research Foundation Site Review Panel member
Geographic Reach Asia 
Policy Influence Type Membership of a guidance committee
 
Description EpiGeneSys
Geographic Reach Asia 
Policy Influence Type Influenced training of practitioners or researchers
URL http://www.epigenesys.eu/en/
 
Description Epigenetics and Chemical Safety ; Rome
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
URL http://www.ecetoc.org/eventsmanager/20/258/Epigenetics-and-Chemical-Safety/
 
Description External Reviewer Epigentics Panel for DFG (German research Council)
Geographic Reach Asia 
Policy Influence Type Membership of a guidance committee
 
Description Science Foudation Ireland
Geographic Reach Asia 
Policy Influence Type Participation in advisory committee
 
Description The Epigenome Network of Excellence (NoE)
Geographic Reach Asia 
Policy Influence Type Influenced training of practitioners or researchers
 
Description BBSRC Research Grant
Amount £600,000 (GBP)
Funding ID BB/E023355/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2007 
End 12/2010
 
Description Breakthrough Breast Cancer Research Unit
Amount £5,000,000 (GBP)
Organisation Breakthrough Breast Cancer 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2007 
End 12/2012
 
Description Epigenetic Landscape Global Nuclear Positioning Tools
Amount £150,000 (GBP)
Funding ID BB/K01384X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2013 
End 08/2014
 
Description Hydroxy-Sensitive Cut Counting (HSCC); simultaneous, genome-wide mapping of 5-methylcytosine and 5-hydroxymethylcytosine in mammals
Amount £150,000 (GBP)
Funding ID BB/J021032/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2012 
End 09/2013
 
Description Mechanisms underlying the transmission of programming effects
Amount £450,000 (GBP)
Funding ID MR/K018310/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2013 
End 07/2016
 
Title DNA methylation inhibitor reporter 
Description WE constructed cells containing a methylated silenced gene lined to a GFP reporter. If the methylation is removed then the gene is active and the cells turn green. Potentially useful for drug screens. 
Type Of Material Cell line 
Provided To Others? No  
Impact An in vivo reporter for DNA methyltransferase inhibitors. 
 
Title Data Sets Generated by work 
Description 1. Dynamic changes in liver 5-hydroxymethylcytosine profiles upon non-genotoxic carcinogen exposure [Replicated control vs. pb treated study] (Submitter supplied) Dynamic changes in the mouse liver DNA methylome associated with short (1 day) and prolonged (7, 28 and 91 days) exposure to the rodent liver non-genotoxic carcinogen (NGC), phenobarbital (PB). Organism: Mus musculus Type: Expression profiling by array Platform: GPL1261 39 Samples FTP download: GEO (CEL) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE45nnn/GSE45465/ Series Accession: GSE45465 ID: 200045465 2. Gene expression in E18.5 Tex19.1-/- mouse placenta (Submitter supplied) Microarray experiment to identify changes in gene expression in 18.5 day post coitum Tex19.1-/- mouse placenta. Tex19.1 is expressed in trophectoderm-derived cells in the placenta. Tex19.1-/- placentas are small and have defects in junctional zone and labyrinth layers of the placenta, Tex19.1-/- embryos exhibit intra-uterine growth retardation. Data provides insight into the changes in gene expression and cell composition in Tex19.1-/- placentas. Organism: Mus musculus Type: Expression profiling by array Platform: GPL6887 12 Samples FTP download: GEO (TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE41nnn/GSE41823/ Series Accession: GSE41823 ID: 200041823 3. Reduced Representation Bisulfite Sequencing in DNA methylation deficient mouse embryonic fibroblasts (Submitter supplied) DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. more... Organism: Mus musculus Type: Methylation profiling by high throughput sequencing Platform: GPL13112 2 Samples FTP download: GEO (TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE44nnn/GSE44760/, SRA SRP018930 ftp://ftp-trace.ncbi.nlm.nih.gov/sra/sra-instant/reads/ByStudy/sra/SRP/SRP018/SRP018930/ Series Accession: GSE44760 ID: 200044760 4. DNA methylation profiling by HELP-seq in Dnmt1+/+ mouse embryonic fibroblasts (Submitter supplied) DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. more... Organism: Mus musculus Type: Methylation profiling by high throughput sequencing Platform: GPL9250 1 Sample FTP download: GEO (BEDGRAPH) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE44nnn/GSE44757/, SRA SRP018929 ftp://ftp-trace.ncbi.nlm.nih.gov/sra/sra-instant/reads/ByStudy/sra/SRP/SRP018/SRP018929/ Series Accession: GSE44757 ID: 200044757 5. mRNA-seq in DNA methylation deficient mouse embryonic fibroblasts (Submitter supplied) DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. more... Organism: Mus musculus Type: Expression profiling by high throughput sequencing Platform: GPL13112 2 Samples FTP download: GEO (TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE44nnn/GSE44733/, SRA SRP018928 ftp://ftp-trace.ncbi.nlm.nih.gov/sra/sra-instant/reads/ByStudy/sra/SRP/SRP018/SRP018928/ Series Accession: GSE44733 ID: 200044733 6. Chip-seq for H3K27me3 and H3K4me3 in DNA methylation deficient mouse embryonic fibroblasts (Submitter supplied) DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. more... Organism: Mus musculus Type: Genome binding/occupancy profiling by high throughput sequencing Platform: GPL11002 4 Samples FTP download: GEO (BEDGRAPH) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE44nnn/GSE44393/, SRA SRP018761 ftp://ftp-trace.ncbi.nlm.nih.gov/sra/sra-instant/reads/ByStudy/sra/SRP/SRP018/SRP018761/ Series Accession: GSE44393 ID: 200044393 7. Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of polycomb-target genes (Submitter supplied) This SuperSeries is composed of the SubSeries listed below. Organism: Mus musculus Type: Expression profiling by array; Genome binding/occupancy profiling by genome tiling array; Methylation profiling by high throughput sequencing; Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 6 related Platforms 35 Samples FTP download: GEO (BEDGRAPH, PAIR) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE44nnn/GSE44278/ Series Accession: GSE44278 ID: 200044278 8. Comparison of gene expression in Dnmt1+/+ and Dnmt1-/- MEFs (Submitter supplied) DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. more... Organism: Mus musculus Type: Expression profiling by array Platform: GPL6887 6 Samples FTP download: GEO (TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE44nnn/GSE44277/ Series Accession: GSE44277 ID: 200044277 9. Comparison of gene expression in Dnmt1+/+ MEFs treated with 5-aza-2'-deoxycytidine or vector control (Submitter supplied) DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. more... Organism: Mus musculus Type: Expression profiling by array Platform: GPL6885 8 Samples FTP download: GEO (TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE44nnn/GSE44276/ Series Accession: GSE44276 ID: 200044276 10. Chip-chip for H3K27me3 and H3K4me3 in DNA methylation deficient mouse embryonic fibroblasts (Submitter supplied) DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. more... Organism: Mus musculus Type: Genome binding/occupancy profiling by genome tiling array Platform: GPL16605 12 Samples FTP download: GEO (PAIR) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE44nnn/GSE44149/ Series Accession: GSE44149 ID: 200044149 11. IP of 5-methylcytosine (5-mC) enriched DNA fragments from control and PB treated mouse livers (28 day) (Submitter supplied) 5-mC is an epigenetic modification of the DNA base cytosine with roles in gene silencing events, imprinting and X inactivation. Phenobarbital (PB) is a well studied non-genotoxic carcinogen with roles in epigenetic perturbation. We profile 5mC in both control mouse livers as well as in the livers of 28 day PB treated mice. 5mC is largely found to reside in the bodies of active genes and promoter levels are perturbed upon PB induced gene activation events. more... Organism: Mus musculus Type: Methylation profiling by genome tiling array Platform: GPL14890 10 Samples FTP download: GEO (PAIR, TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE40nnn/GSE40538/ Series Accession: GSE40538 ID: 200040538 12. IP of 5-hydroxymethylcytosine (5-hmC) enriched DNA fragments from control and PB treated mouse livers (28 day) (Submitter supplied) 5-hmC is a novel epigenetic mark derived from oxidation of methylcytosine. Phenobarbital (PB) is a well studied non-genotoxic carcinogen with roles in epigenetic perturbation. We profile 5hmC in both control mouse livers as well as in the livers of 28 day PB treated mice. 5hmC is largely found to reside in the bodies of active genes and promoter levels are perturbed upon PB induced gene activation events. more... Organism: Mus musculus Type: Methylation profiling by genome tiling array Platform: GPL14890 10 Samples FTP download: GEO (PAIR, TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE40nnn/GSE40537/ Series Accession: GSE40537 ID: 200040537 13. IP of 5-hydroxymethylcytosine (5-hmC) and 5-methylcytosine (5-mC) enriched DNA fragments from control and PB treated mouse livers (Submitter supplied) This SuperSeries is composed of the SubSeries listed below. Organism: Mus musculus Type: Methylation profiling by genome tiling array; Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing 6 related Platforms 153 Samples FTP download: GEO (BEDGRAPH, CEL, PAIR) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE40nnn/GSE40540/ Series Accession: GSE40540 ID: 200040540 14. Dynamic changes in liver 5-hydroxymethylcytosine profiles upon non-genotoxic carcinogen exposure (Submitter supplied) 29-32 days old male mice where either treated with Phenobarbital or untreated Organism: Mus musculus Type: Expression profiling by array Platform: GPL1261 10 Samples FTP download: GEO (CEL) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE40nnn/GSE40773/ Series Accession: GSE40773 ID: 200040773 15. Promoter DNA methylation couples genome-defense mechanisms to epigenetic reprogramming in the mouse germline (Submitter supplied) This SuperSeries is composed of the SubSeries listed below. Organism: Mus musculus Type: Expression profiling by array Platforms: GPL6885 GPL6887 5 Samples FTP download: GEO ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE38nnn/GSE38307/ Series Accession: GSE38307 ID: 200038307 
Type Of Material Biological samples 
Year Produced 2012 
Provided To Others? Yes  
Impact Available for Meta analysis by other groups 
URL http://www.ncbi.nlm.nih.gov/gds
 
Title Data sets Part II 
Description 16. Promoter DNA methylation couples genome-defense mechanisms to epigenetic reprogramming in the mouse germline (part 2) (Submitter supplied) Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of the comprehensive epigenetic reprogramming that occurs during PGC development. 5mC plays an important role in maintaining stable gene silencing and repression of transposable elements (TE) but it is not clear how the extensive loss of DNA methylation impacts on gene expression and TE repression in developing PGCs. Using a novel epigenetic disruption and recovery screen and genetic analyses, we identified a core set of germline-specific genes that are dependent exclusively on promoter DNA methylation for initiation and maintenance of developmental silencing. more... Organism: Mus musculus Type: Expression profiling by array Platform: GPL6885 2 Samples FTP download: GEO (TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE38nnn/GSE38306/ Series Accession: GSE38306 ID: 200038306 17. Promoter DNA methylation couples genome-defense mechanisms to epigenetic reprogramming in the mouse germline (part 1) (Submitter supplied) Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of the comprehensive epigenetic reprogramming that occurs during PGC development. 5mC plays an important role in maintaining stable gene silencing and repression of transposable elements (TE) but it is not clear how the extensive loss of DNA methylation impacts on gene expression and TE repression in developing PGCs. Using a novel epigenetic disruption and recovery screen and genetic analyses, we identified a core set of germline-specific genes that are dependent exclusively on promoter DNA methylation for initiation and maintenance of developmental silencing. more... Organism: Mus musculus Type: Expression profiling by array Platform: GPL6887 3 Samples FTP download: GEO (TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE38nnn/GSE38305/ Series Accession: GSE38305 ID: 200038305 18. Gene expression in 16 dpp Tex19.1-/- mouse testes (Submitter supplied) Microarray experiment to identify changes in gene expression in 16 day post partum prepubertal Tex19.1-/- mouse testes. Tex19.1 is expressed in germ cells in testes. Tex19.1-/- mice have spermatogenic defects and errors in progression through meiosis. Data provides insight into the changes in gene expression in developing testes at the time when meiotic defects first start to become apparent. Organism: Mus musculus Type: Expression profiling by array Platform: GPL6887 8 Samples FTP download: GEO (TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE30nnn/GSE30461/ Series Accession: GSE30461 ID: 200030461 19. Hydroxymethyl DNA-IP of genomic DNA for many different normal human tissues (Submitter supplied) 5-hmC is a novel epigenetic mark derived from oxidation of methylcytosine. We profile this mark in several normal human tissues 5-hmC patterns are highly tissue specific and enriched in the body of transcribed genes 5-hmC patterns are highly tissue specific and enriched in the body of transcribed genes Organism: Homo sapiens Type: Methylation profiling by genome tiling array Platform: GPL14788 14 Samples FTP download: GEO (PAIR) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE33nnn/GSE33219/ Series Accession: GSE33219 ID: 200033219 20. Analysis of Promoter Methylation in Breast Cancer (Submitter supplied) Promoter methylation was assayed in a number of breast cancer and control normal samples along with the effects of 5'-aza-2'-deoxycytidine on breast cancer cell line transcriptomes. Aberrant promoter hypermethylation is frequently observed in cancer. The potential for this to contribute to tumour development depends on whether the genes affected are repressed because of their methylation. Many aberrantly methylated genes play important roles in development and are bivalently marked in ES cells suggesting that their aberrant methylation may reflect developmental processes. more... Organism: Homo sapiens Type: Methylation profiling by array; Expression profiling by array Platforms: GPL8490 GPL6947 107 Samples FTP download: GEO (TXT) ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE26nnn/GSE26990/ Series Accession: GSE26990 ID: 200026990 
Type Of Material Biological samples 
Year Produced 2012 
Provided To Others? Yes  
Impact Avaialable for Meta analysis by other groups 
URL http://www.ncbi.nlm.nih.gov/gds
 
Title H-DIP 
Description We developed a technique to map athe newly modified base 5-hydroxymethylcytosine in geneomic DNA. 
Type Of Material Biological samples 
Year Produced 2010 
Provided To Others? Yes  
Impact 3 high impact publications, with more to follow. 
URL http://genomebiology.com/content/13/10/R93
 
Title Indentification of genes regulated directly by DNA methylation 
Description We developed a 'recovery' assay that allows identification of genes that are strictly regulated by DNA methylation through exposure to epigenetic disruptors. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2009 
Provided To Others? Yes  
Impact Too early to say 
URL http://dev.biologists.org/content/139/19/3623.long
 
Title Non-canonical roles for DNMT1 
Description Expression clones for Xenopus Dnmt1. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2008 
Provided To Others? Yes  
Impact We identified a signaling pathway by which apoptosis is induced in XDnmt1 depleted embryos. we believe this is an important pathway that is not fully functional in cancer cells that have an altered DNA methylation profle as a result of mis-regulation of DNMT1. 
 
Title methyl CpG binding proteins 
Description During my post-doctral career I identified and characterised the first methyl-CpG binding activities and subsequently methyl-CpG binding protein, MeCP2. These factors fitted a model whereby cytosine methylation at promoter sequences can result in gene silencing that is mediated by the binding of these proteins at promoter proximal regions. Now there are several methyl-CpG binding proteins. We identified the methyl-CpG-binding motif (MBD domain) of MeCP2 and its structure has subsequently been determined by nuclear magnetic resonance analysis. The domain adopts a wedge-shaped structure containing a four-stranded antiparallel ß sheet at the amino terminus as one face and a helical region at the carboxy terminus as another face. This finding suggested that methyl-CpG binding proteins do not have a sequence preference in vitro and this property has been used to selectively enrich for in vivo or in vitro methylated sequences. 
Type Of Material Technology assay or reagent 
Year Produced 2006 
Provided To Others? Yes  
Impact Either for direct sequencing and analysis or for screening arrays to identify methylated sequences that occur during normal development or that have occurred de novo in cancer. 
 
Description MARCAR (Mechanism-driven development of early biomarkers and molecular tumor classification for non-genotoxic carcinogenesis) 
Organisation European Commission
Department Innovative Medicines Initiative (IMI)
Country Belgium 
Sector Public 
PI Contribution I am part of a consortium (MARCAR) that after a competitive application process, has been selected by the Innovative Medicines Initiative (IMI) to negotiate a 3-5 year program of work that aims to improve the predictivity of safety evaluation in non-genotoxic carcinogenesis. We proposed a research program that includes epigenetic analysis of novel model systems and unique archived material of industrial partners (EFPIA). If the application proceeds successfully, there will be matching (in-kind) funds from EFPIA members. An ultimate aim of the research program is to identify new biomarkers for non-genotoxic carcinogenesis in liver.
Collaborator Contribution I am part of a consortium (MARCAR) that after a competitive application process, has been selected by the Innovative Medicines Initiative (IMI) to negotiate a 3-5 year program of work that aims to improve the predictivity of safety evaluation in non-genotoxic carcinogenesis. We proposed a research program that includes epigenetic analysis of novel model systems and unique archived material of industrial partners (EFPIA). If the application proceeds successfully, there will be matching (in-kind) funds from EFPIA members. An ultimate aim of the research program is to identify new biomarkers for non-genotoxic carcinogenesis in liver.European networking, the application of epigenetics to toxicology testing. New interaction with NHI (US) funded agencies and colleagues. The successful application for Funding from IMI (EU) to commence in January 2009.
Impact I am part of a consortium (MARCAR) that after a competitive application process, has been selected by the Innovative Medicines Initiative (IMI) to negotiate a 3-5 year program of work that aims to improve the predictivity of safety evaluation in non-genotoxic carcinogenesis. We proposed a research program that includes epigenetic analysis of novel model systems and unique archived material of industrial partners (EFPIA). If the application proceeds successfully, there will be matching (in-kind) funds from EFPIA members. An ultimate aim of the research program is to identify new biomarkers for non-genotoxic carcinogenesis in liver.
Start Year 2007
 
Title Gene regulation 
Description The present invention relates to methods of identifying genes which are primarily and causally regulated by epigenetic events such as, for example, DNA methylation. The invention also provides uses of such genes and transgenic animals. 
IP Reference GB1014818.7 
Protection Patent application published
Year Protection Granted 2010
Licensed Commercial In Confidence
Impact Too early to say
 
Description 2006 Taiwan Society for Stem Cell Research 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I attended and spoke at the Annual meeting for "Taiwan Society for Stem Cell Research".I presented a lecture on my work on epigenetics and development. The meeting was directly related to the goal of my present work in terms of understanding cellular pluipotency and the stability of epigenetic mechanisms in stem cells and development. It was a great opportunity to meet with fellow workers and world experts in the field and to reciprocate the visit of a Taiwanese delegation to Scotland that was held on October 2005.

The conference was a major news item in Taiwan and at the conference a new programm of research was annouced by the Taiwanese minster for Science.
Year(s) Of Engagement Activity 2006
 
Description 2009 Rank Prize Fund (Nutritional Epigenomics), 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussion on the role of environmental toxins that may be epigenetic modifiers.

Still on-going
Year(s) Of Engagement Activity 2009
 
Description 47th Congress of the European Societies of Toxicology. August 28-31, 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Epigenetics as a biomarker for drug exposure

New collaborations developed
Year(s) Of Engagement Activity 2011
 
Description 5hmC Workshop Biochem Soc 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact The New Epigenetic Mark: 5-Hydroxymethylcytosine - What is its Function?
13 June 2013: Cancer Research UK Cambridge Institute, UK
Title: Knowing me, Knowing you. Ahaaaa! 5hmC and the Epigenetics of identity


I made a you tubre presentation to explain the topic.

http://www.youtube.com/watch?v=0EXzIOw4hNg
Year(s) Of Engagement Activity 2013
URL http://www.biochemistry.org/tabid/379/MeetingNo/HT006/view/Programme/default.aspx
 
Description COTOX Presentation and subsequent review of the resulting report 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact An oral presenation to the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) at its meeting in Prestbury, near Manchester on 6 February 2008. This presentation would included an introduction to epigenetics together with consideration of the role of DNA methylation in development, disease and its perturbation by environmental toxins. Feed back was positive and resulted in a written report statement on the Transgenerational Epigenetics workshop has now published on the Committee's website - see the link below. http://cot.food.gov.uk/cotstatements/cotstatementsyrs/cotstatements2008/cot200803

COT Conclusions 46. There is reasonable evidence that epigenetic changes associated with environmental exposures during development can result in adverse effects. Such effects might be detected in the F1 and F2 generations by standard regulatory toxicity testing. 47. Transgenerational epigenetic inheritance of effects in the F3 generation and beyond would also be of potential relevance to risk assessment. If epigenetic inheritance does occur, it is possible that this could lead to an accumulation in risk across generations. In addition, such epigenetic changes could be developed as biomarkers of effect. 48. However, the science is not yet developed and therefore assessment of transgenerational epigenetic inheritance cannot be incorporated in regulatory risk assessment at present. 49. It is still unclear whether transmission of environmentally acquired epigenetic changes across generations occurs in humans and if so, what mechanisms of epigenetic modification are important. 50. Priorities for future research include assessment of whether important examples of epigenetic inheritance seen in animals also occur in humans. In addition, it may be useful to investigate aberrant phenotypes in humans which might possibly have a transgenerational, epigenetic basis. It is feasible to undertake genome wide profiling to ascertain if changes in DNA methylation patterns underlie environmentally acquired epigenetic changes that occur in experimental models and perhaps human populations.
Year(s) Of Engagement Activity 2008
URL http://cot.food.gov.uk/cotstatements/cotstatementsyrs/cotstatements2008/cot200803
 
Description Chair and platform speaker European Epigenetics meeting. 14-15th September, Dublin, Ireland. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Discussions with lifscience stakeholder on the role of Epigenetics in disease and as a potential biomarker for drug exposure

New collaborations ensued
Year(s) Of Engagement Activity 2010,2011
 
Description CoTox Transgenerational epigenetics workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Discussion on the role of environmental toxins that may be epigenetic modifiers, with a view to the impact on human health.

Resulting invitations to speak and lead discussions at The 2009 National Academy Sciences Environmental Epigenetics Workshop, Washington, July 30-31. The HESI WORKSHOP ON THE STATE OF THE SCIENCE OF EPIGENETICS OCTOBER 28-30, 2009, North Carolina, USA. Contributed to participation in MARCAR, which will study early epigenetic changes in response to non-genotoxic carcinogenes.
Year(s) Of Engagement Activity 2008
 
Description Dundee Personalised Medicine meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Discussions with Clinicians and non-clinicians on the role of Epigenetics in disease and as a potential biomarker

New collaborations ensued
Year(s) Of Engagement Activity 2010
 
Description FEBS Workshop Denmark 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I presented two lectures; one present trends in Epigenetics Research and a second on my own research programs.

My talks stimulated much debate and questions.
Year(s) Of Engagement Activity 2012
 
Description HESI, North Carolina 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 150 ; General audience of scientists, including toxicologists, precipitating many questions on the possibility of environmental exposure leading to disruption of epigenetic pathways.

Planning of future experiments with a view to testing new ideas in 2010 and 2011
Year(s) Of Engagement Activity 2009
 
Description HUGO 2007 Platfom Speaker Symposium IV 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The scientific programme for HGM2007 to an international audience of scientists and clinicians was focussed on worldwide progress in the Human Genome Project and the programme included sessions on: · Large-Scale Medical Resequencing · Genome Wide Association Studies in depth analysis of the human genome · Genomic Variation · Genomic Medicine - Global Perspectives · Regulatory RNAs · Epigenomics · Genetics of Infectious Diseases · Neuropsychiatric Genetics I spoke in the Epigenomics session

Theconference was reported on daily by national (Canada) and international media sources.
Year(s) Of Engagement Activity 2007
 
Description ICE-2008: Oral presentation and member of review panel 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact The ICE-2008 is the final conference of the priority program SPP1129 of the Deutsche Forschungsgemeinschaft (funding period 2002 - 2008) for which I was an external reviewer. The conference is funded by the Deutsche Forschungsgemeinschaft (DFG).

Forged new links between DFG grant holders and UK (mainly BBSRC) funded researchers on epigenetics.
Year(s) Of Engagement Activity 2008
URL http://epigenetics.uni-saarland.de/en/spp1129/
 
Description Next-Gen Sequencing Europe conference Hamburg, June 30 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact THe of a new 6th base, 5-hydroxymethylcytosine, on epigenetics

New collaborations ensued
Year(s) Of Engagement Activity 2011
 
Description Rome: Epigenetics and Chemical Safety 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact The workshop addressed the following aspects:

examine scientific and technological approaches to identify and quantify epigenetic effects of chemicals and to assess their potential effects on human health and ecology.

consider the strengths and weaknesses and the costs and benefits of looking at epigenetic effects of chemicals by using new approaches and technologies.

In particular the workshop addressed the following points:

Definition of epigenetic changes and effects in the context of (eco-) toxicology.
What are the consequences of epigenetic changes induced by exogenous substances on human and environmental health?
Is the current way of assessing the safety of chemicals able to detect adverse effects related to epigenetic changes?
Case studies: implications of epigenetics in adverse effects in Humans, in animal models and ecotoxicology


WE produced a report.
http://www.ecetoc.org/index.php?mact=MCSoap,cntnt01,details,0&cntnt01by_category=22&cntnt01order_by=date%20Desc&cntnt01template=display_list_v2&cntnt01display_template=display_details_v2&cntnt01document_id=6329&cntnt01returnid=59

WR 23 : ECETOC WR 23 - Epigenetics and Chemical Safety | 18 June 2012

Epigenetics is a rapidly developing and expanding biological science which will change our perception of cell biology in a profound way. In order to increase our knowledge of how epigenetics could have an impact in (eco)toxicology, a solid understanding of the biology and variation of the epigenome is essential to better assess concerns about possible adverse health effects related to epigenetic changes.
Year(s) Of Engagement Activity 2011
URL http://www.ecetoc.org/index.php?mact=XtendedCalendar,cntnt01,details,0&cntnt01documentid=41&cntnt01r...
 
Description Syngenta Sponsored Workshop on Epigenetics - 24th - 25th September 2007 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Discussion of the possibility that exposure to certain compounds may result in epigenetic dysregulation.

Brain storming session on the role of epigenetics in toxicology assessment and exposure.
Year(s) Of Engagement Activity 2007
 
Description Washington National Acadamey 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact 100 stake holders (including science media) attanded with a subsequent Q and A session

Subsequent invite to HESI workshop on the state of the science of epigenetics in North Carolina
Year(s) Of Engagement Activity 2009
 
Description Workshop at Syngenta, Bracknell, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Discussion on the role of environmental toxins that may be epigenetic modifiers.

Resulting invitations to speak and lead discussions at Transgenerational epigenetics workshop organised by Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) 7th February 2008. The 2009 National Academy Sciences Environmental Epigenetics Workshop, Washington, July 30-31. The HESI WORKSHOP ON THE STATE OF THE SCIENCE OF EPIGENETICS OCTOBER 28-30, 2009, North Carolina, USA. Contributed to participation in MARCAR, which will study early epigenetic changes in response to non-genotoxic carcinogenes.
Year(s) Of Engagement Activity 2007
 
Description Workshop on Epigeneticsand Chemical Safety 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact My talk on new methods for assessing epigentic perturnations was well received and stimulated much debate and questions.

We produced a report that was published in 2012 that was entitled 'Epigenetics and Chemical Safety'.
Year(s) Of Engagement Activity 2011