Objectif My central question: how does the human placenta develop and how are specialized trophoblast sub-types generated? Despite advances in placental biology, pregnancy disorders occur frequently with few treatment options available, resulting in considerable maternal and/or infant mortality and morbidity. The cause of these disorders is abnormal early placental development but ethically and practically this is hard to investigate. Developing in vitro models that are truly representative of normal first trimester trophoblast will allow investigation of lineage specification and differentiation. I will take an interdisciplinary approach to characterize the first trimester villous cytotrophoblast (VCT) population. Specifically, I aim to:1. Characterize the expression of trophoblast stem (TS) cell transcription factors and epigenetically regulated genes to identify the anatomical compartment(s) containing population(s) with stem cell characteristics2. Isolate VCT using a specific cell surface marker and perform an in-depth molecular characterization at a single cell level to identify putative TS cells3. Characterize cell signalling pathways in the VCT and in the putative TS cell population4. Establish cell culture conditions for TS cells5. Perform a detailed characterization of cells cultured in vitroThis proposal has arisen from preliminary results obtained working in Centre for Trophoblast Research, University of Cambridge. Working in a lab with extensive experience of trophoblast isolation (Prof. A.Moffett) and input from our collaborators, Dr. M.Hemberger and Prof. G.Burton who have experience in mouse TS cells and human placental function in vivo, respectively has been pivotal. I am thus in an ideal position to capitalize on this expertise together with other stem cell labs in Cambridge to develop essential tools and knowledge to understand early developmental processes during placentation. It also has important translational impact for women and their babies. Champ scientifique social sciencessociologydemographymortalitynatural sciencesbiological sciencescell biologycell signalingmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineobstetrics 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) Thème(s) FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Appel à propositions FP7-PEOPLE-2013-IEF Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Contribution de l’UE € 231 283,20 Adresse TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Royaume-Uni Voir sur la carte Région East of England East Anglia Cambridgeshire CC Type d’activité Higher or Secondary Education Establishments Contact administratif Renata Schaeffer (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée