Objectif "Cellular replacement therapies for treating degenerative diseases such as Alzheimer’s will require the generation of lost tissues by reprogramming cell types. While one strategy is to de-differentiate somatic cells into induced pluripotent stem cells with subsequent re-differentiation, an alternative strategy is to directly convert cells to the target cell type by using specific Transcription Factors (TFs). The latter strategy utilizes TFs that can induce specific cell fates; however, their ability to reprogram cell identities upon mis-expression is very limited. We are elucidating refractory mechanisms of direct cell fate conversion using C. elegans as a model organism. Using RNAi screens we recently identified LIN-53 (homolog of Rbbp4/7) as an inhibitor of reprogramming mitotic germ cells directly into specific neurons and muscle-like cells. At least six different chromatin regulatory complexes such as NURF/NuRD remodeling and histone modifying complexes share LIN-53. However, the molecular function of LIN-53 in different tissues and its exact role in regulating reprogramming remains elusive. Furthermore, forward genetics screens identified a ubiquitin specific protease (USP) to be involved in regulating direct reprogramming of hypodermal (skin) cells in worms. Nothing is known about this USP, only that its homolog is a direct target of the ectodermal master regulator p63 in human skin cells. Using 4D time-lapse imaging and tissue-specific biochemistry (ChIP-seq, SILAC) we aim to determine the spatio-temporal expression pattern of both factors in vivo and investigate their molecular function in controlling cell fate reprogramming. We will elucidate the regulatory network of these reprogramming factors by complementing our examinations with genetic analysis. Our findings might have broad implications for understanding mechanisms that restrict direct cell fate reprogramming and for generating specific tissues from different cellular contexts." Champ scientifique natural sciencesbiological sciencesbiochemistrynatural sciencesbiological sciencesgeneticsmedical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesmedical biotechnologycells technologiesstem cells 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-2012-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2012-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) Contribution de l’UE € 100 000,00 Adresse ROBERT ROSSLE STRASSE 10 13125 Berlin Allemagne Voir sur la carte Région Berlin Berlin Berlin Type d’activité Research Organisations Contact administratif Ioannis Legouras (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée