Objetivo It is now know that the mammalian genome encodes many thousands of long non-coding RNAs (lncRNAs, >200nt long), some of which are implicated in human pathogenesis including cancers. A subset of lncRNAs such as HOTAIR and ANRIL are overexpressed in several cancers and play roles in epigenetic gene regulation during carcinogenesis, mainly by recruiting chromatin modifier complexes to their target loci. Interestingly, recent studies indicate that some lncRNAs including ANRIL bind to and act together with other chromatin binding proteins (CBPs) that recognize specific histone modifications. However, lncRNA research is still in its infant stage and physical and functional links among lncRNAs, CBPs and histone modifications have not yet been studied extensively. Moreover, considering the facts that the levels of some CBPs change during carcinogenesis, it is likely that different repertoires of lncRNAs-CBP complexes exist in normal and cancer cells.Based on these facts, I hypothesize that cell type-specific repertoires of lncRNA-CBP complexes lead to altered readouts of specific histone modifications and ultimately contribute to formation/progression of cancer. Using breast cancer cell lines as model systems, I aim to identify repertoires of lncRNA-CBP complexes associated with cancer-related histone modifications (methyl-H3Lys9/27) in normal and cancer cells and unravel their oncogenic or tumour suppressor functions in vivo using proteomics, genomics, molecular and cell biology approaches. In particular, I will develop a novel, highly versatile method for efficient identification of multiple lncRNA-CBP complexes, by combining photo-mediated RNA crosslinking to proteins, nucleosome-based pulldown and quantitative SILAC mass spectrometry. I believe that the outcome of this project will provide novel and deeper insights into the interplay among lncRNAs, CBPs and histone modifications in carcinogenesis, which can be applied to translational medicine in the future. Ámbito científico natural sciencesbiological sciencescell biologymedical and health sciencesclinical medicineoncologybreast cancernatural sciencesbiological sciencesgeneticsRNAnatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesbiological sciencesgeneticsgenomes Programa(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) Tema(s) FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Convocatoria de propuestas FP7-PEOPLE-2012-IEF Consulte otros proyectos de esta convocatoria Régimen de financiación MC-IEF - Intra-European Fellowships (IEF) Coordinador MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Aportación de la UE € 216 952,80 Dirección HOFGARTENSTRASSE 8 80539 Munchen Alemania Ver en el mapa Región Bayern Oberbayern München, Kreisfreie Stadt Tipo de actividad Research Organisations Contacto administrativo Wolfgang Fischle (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
