Objective During differentiation, cells undergo large-scale chromatin rearrangement, notably with the establishment of heterochromatin blocks at the nuclear periphery during the epiblast stage of development. Concomitantly, hundreds of genes are relocated to and from the nuclear periphery and their position is correlated with their expression levels. Most of these genes are associated with regulation of pluripotency, suggesting that the association of fLADs to the NL is a key parameter for proper embryonic development. Recent work of the host lab using synthetic activators showed that the chromatin rearrangement is responsible for the relocation of these genes. However, the mechanisms that govern this chromatin rearrangement are largely unknown. Here I propose to test whether a modulation of nuclear pore density allows chromatin reorganization during differentiation of embryonic stem cells (ESCs) into epiblast stem cells (EpiSCs), laying the groundwork for future analysis in vivo during embryonic development. As a complementary approach, I will determine the mechanisms that prevent heterochromatin formation at nuclear pore complexes. The use of state of the art techniques such as super-resolution microscopy, genome mapping and a multidisciplinary approach combining biology and physics will allow me to understand the role of nuclear pore complexes in the regulation of genome organization. Fields of science natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopynatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsgenomes Programme(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 Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator THE UNIVERSITY OF EDINBURGH Net EU contribution € 195 454,80 Address OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh United Kingdom See on map Region Scotland Eastern Scotland Edinburgh 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 € 195 454,80
