Objetivo One of the most critical epigenetic and chromatin remodelling processes in mammalian development occurs shortly after fertilization restoring totipotency. Due to limited cell numbers and lack of experimentally tractable systems, the mechanisms and regulation of this developmental stage are poorly understood. This proposal will provide important mechanistic insights into the epigenetic control of early embryonic gene expression, and its relevance to somatic reprogramming. Murine embryonic stem cells (ESCs) contain a rare sub-population of early embryonic like (EEL) cells expressing genes normally restricted to the pre-implantation embryo, with enhanced extra-embryonic differentiation capability. Firstly, using novel single-cell technologies, I will characterize the EEL cells in detail, validating them as an in vitro model of pre-implantation development. On-going research in the host lab that I am involved in has identified an epigenetic enhancer that expands this EEL sub-population. Through bioinformatic analysis of pre-implantation transcriptome data, I have shortlisted 34 epigenetic and chromatin-associated proteins, including the previously identified factor, which will be systematically screened to identify new enhancers of totipotency. Validated EEL regulators, including two additional newly confirmed factors, will be analysed mechanistically determining their interaction partners, interdependencies, and mode of action. Finally, the contribution of the totipotency regulators towards the efficiency and fidelity of somatic reprogramming will be determined, potentially improving the use of this technology for personalised gene therapy and regenerative medicine.This state-of-the-art proposal uses innovative and novel cutting-edge technologies and combines the expertise of the researcher and the host. It has the potential for significant impact across several fields from epigenetics and stem cell biology to reprogramming and regenerative medicine. Ámbito científico medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineembryologynatural sciencesbiological sciencesgeneticsepigenetics Programa(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Tema(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Convocatoria de propuestas H2020-MSCA-IF-2014 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-EF-ST - Standard EF Coordinador THE BABRAHAM INSTITUTE Aportación neta de la UEn € 183 454,80 Dirección Babraham Hall CB22 3AT Cambridge Reino Unido Ver en el mapa Región East of England East Anglia Cambridgeshire CC Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 183 454,80