Objective Germ cells serve the critical function of transmitting genetic and epigenetic information across generations in multi-cellular organisms. An important attribute of the germ line is to generate the totipotent state. Studies of this unique cell lineage are of wide general interest in the context of stem cells and mechanisms of pluripotency. Relatively little is yet known about how germ cells are specified in mice. Recent genetic studies showed that the transcriptional repressor Blimp1 is a critical determinant of germ cell fate in the epiblast cells of the mouse embryo. There are only about 35 founder primordial germ cells (PGCs) present in each embryo, providing a significant hurdle for the mechanistic elucidation of germ cell specification. A robust in-vitro system that mimics PGC specification is essential to gain a deeper insight into the role of Blimp1 in germ cell fate determination. This project aims to generate such a system using a twofold approach. First, by engineering embryonic stem cells to express Blimp1 in an inducible manner and utilizing them for the induction of PGC fate. Second, by generating transgenic mice expressing fluorescent reporter molecules, for the derivation of epiblast stem cell cultures and subsequent FACS sorting of PGCs. To elucidate the gene expression programme governed by Blimp1 during PGC specification, the culture models will be used for analysis of the genome wide target site binding of Blimp1 and performing functional assays of the target genes and co-repressor proteins bound with Blimp1 to the sites identified. This will likely provide novel biochemical insight into PGC specification revealing mechanisms underlying the balance between pluripotency and differentiation. The project will provide training to the fellow in terms of techniques and subjects pertaining to stem cells, germ cells, mouse genetics and development, while at the same time allowing the re-integration of the fellow into the European scientific community. Fields of science natural sciencesbiological sciencesbiochemistrymedical and health sciencesmedical biotechnologygenetic engineeringmedical and health sciencesmedical biotechnologycells technologiesstem cells Keywords Mouse developmental biology Natural sciences chromatin embryonic stem cells epigenetics lineage specification primordial germ cells stem cells transcription factors Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-IEF-2008 - Marie Curie Action: "Intra-European Fellowships for Career Development" Call for proposal FP7-PEOPLE-IEF-2008 See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE EU contribution € 181 350,76 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Edna Murphy (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
