Objective Development of any organism starts with a totipotent cell (zygote). Through series of cell divisions and differentiation processes this cell will eventually give rise to the whole organism containing hundreds of specialised cell. While the cells at the onset of development have the capacity to generate all cell types (ie are toti-or pluripotent), this developmental capacity is progressively lost as the cells undertake cell fate decisions. At the molecular level, the memory of these events is laid down in a complex layer of epigenetic modifications at both the DNA and the chromatin level. Unidirectional character of the developmental progress dictates that the key acquired epigenetic modifications are stable and inherited through subsequent cell divisions. This paradigm is, however, challenged during cellular reprogramming that requires de-differentiation (nuclear transfer, induced pluripotent stem cells, wound healing and regeneration in lower organisms) or a change in cell fate (transdifferentiation). Despite intense efforts of numerous research teams, the molecular mechanisms of these processes remain enigmatic. In order to understand cellular reprogramming at the molecular level, this proposal takes advantage of epigenetic reprogramming processes that occur naturally during mouse development. By using mouse fertilised zygote and mouse developing primordial germ cells we will investigate novel molecular components implicated in the genome-wide erasure of DNA methylation. Additionally, by using a unique combination of the developmental models with the state of the art ultra-sensitive LC/MS and genomics approaches we propose to investigate the dynamics and the interplay between DNA and RNA modifications during these key periods of embryonic development characterised by genome-wide epigenetic changes . Our work will thus provide new fundamental insights into a complex dynamics and interactions between epigenetic modifications that underlie epigenetic reprogramming Fields of science natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesclinical medicineembryologynatural sciencesbiological sciencesgeneticsepigenetics Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2014 - ERC Consolidator Grant Call for proposal ERC-2014-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Net EU contribution € 2 000 000,00 Address SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 000 000,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE United Kingdom Net EU contribution € 2 000 000,00 Address SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 000 000,00