Objectif Epigenetic pathways contribute to cancer development and progression. These pathways act via proteins that modulate chromatin structure and gene expression, and can thereby give pro-proliferative and anti-apoptotic properties selected for in cancer. In total ~400 factors are known that either modify chromatin directly as epigenetic ‘writers’ (DNA methyltranserases, histone methyltransferases, acetyltransferases, kinases, ubiquitinases) and ‘erasers’ (histone demethylases, deacetylases, phosphatases, deubiquitinases) or indirectly by moving nucleosomes (‘remodelers’) or binding to the modifications set by the ‘writers’ (‘readers’; e.g. bromo, PHD, chromo, tudor domains). Small molecules inhibiting several chromatin modifying enzymes have been developed, and HDAC inhibitors and DNA methyltransferase inhibitors are approved drugs. While DNA methyltransferases and histone deacetylases are well-established drug-targets, the majority of the ~400 chromatin modifiers is not studied in cancer. Furthermore, the functional link between genetic alterations of the genes encoding these enzymes and increased proliferation in a cancerous state is less well established.Here we propose to generate and apply tools to systematically study these proteins in cancer using epigenome-wide knock-down studies and small molecule probes. This project directly benefits from the experience at the Broad Institute, where Stefan Kubicek worked for 3.5 years, which allowed him to bring to CeMM a library of knock-down constructs targeting all chromatin proteins in collaboration with the Broad RNAi platform. Similarly, his work on histone demethylases has yielded interesting probe compounds, and his continuing collaboration is recognized by his continuing status as a Remote Associate Researcher of the Broad Institute Chemical Biology Program. Stefan Kubicek started at CeMM in August 2010 and funding of this EPICAL proposal will allow to further integrate his career in the European research space. Champ scientifique natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesbiological sciencesgeneticsepigenetics 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-2011-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2011-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH Contribution de l’UE € 100 000,00 Adresse LAZARETTGASSE 14 AKH BT 25.3 1090 Wien Autriche Voir sur la carte Région Ostösterreich Wien Wien Type d’activité Private for-profit entities (excluding Higher or Secondary Education Establishments) Contact administratif Angelika Eisner (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
