Objetivo The aim of this proposal is to understand how self-renewal is controlled in neural stem cell lineages and how defects in this process can lead to the formation of brain tumors in model organisms. The system we use are Drosophila neuroblasts, stem cell like progenitors in the developing fly brain that undergo repeated rounds of asymmetric cell division. During each division, protein determinants called Numb, Prospero and Brat are segregated into one of the daughter cells where they stop self-renewal and ultimately trigger neuronal differentiation. Mutations in those proteins or their segregation machinery lead to the formation of tumor neuroblasts, which proliferate indefinitely leading to the formation of a deadly brain tumor. The approach we take is to determine the transcriptional network that acts in neuroblasts to control self-renewal. We will use time-resolved transcriptional profiling to determine, how this network changes in the differentiating daughter cell and develop tools for medium-throughput functional analysis of the key network players. We will develop methodology for tissue-specific chromatin immunoprecipitation to determine, how the asymmetrically segregating determinants feed into this network. Using this data set, we will determine the pathological state of the network in the tumorigenic situation. We will determine, how wild type neural stem cells limit their proliferation capacity and how those control mechanisms are affected in the tumor situation. Ultimately, we will expand this analysis to other stem cell systems inside and outside the fly nervous system to determine how modifications of stem cell systems like transit amplifying pools or perpetual adult proliferation are reflected in network architecture. Ámbito científico natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationnatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysis Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-AG-LS3 - ERC Advanced Grant - Cellular and Developmental Biology Convocatoria de propuestas ERC-2009-AdG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH Aportación de la UE € 2 499 875,00 Dirección DR BOHRGASSE 3 1030 Wien Austria Ver en el mapa Región Ostösterreich Wien Wien Tipo de actividad Private for-profit entities (excluding Higher or Secondary Education Establishments) Contacto administrativo Tanja Winkler (Ms.) Investigador principal Juergen Knoblich (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH Austria Aportación de la UE € 2 499 875,00 Dirección DR BOHRGASSE 3 1030 Wien Ver en el mapa Región Ostösterreich Wien Wien Tipo de actividad Private for-profit entities (excluding Higher or Secondary Education Establishments) Contacto administrativo Tanja Winkler (Ms.) Investigador principal Juergen Knoblich (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
