Objetivo The cell nucleus is positioned at specific places within the cytoplasm and this position is important for different cellular, developmental and physiological processes. Nuclear positioning depends on connections between nuclear envelope proteins and the cytoskeleton. In migrating cells, we found that the nucleus is positioned away from the front of the cell and this event is important for cell migration. We performed an RNAi screen for nuclear positioning and found new nuclear envelope proteins involved in nuclear positioning. In fully developed myofibers, nuclei are specifically positioned at the periphery of the myofiber, while during development and regeneration, as well as in multiple muscle pathologies, the nucleus is centrally positioned. We found new mechanisms drive nuclear movement during myofiber formation. We also showed that nuclear position is important for muscle function. However why nuclear positioning is important for myofiber activity remains an open question.We now propose to use unique systems to monitor cell migration and myofiber formation in combination with biochemistry, cell biology, high- and super-resolution microscopy approaches to:1) Identify novel molecular mechanisms that mediate nuclear positioning during cell migration and myofiber formation.3) Determine a role for nuclear positioning in myofiber function as well as the significance of altered nuclear positioning in different forms of muscle pathology.The proposed work will establish new mechanisms for nuclear positioning. Importantly, by identifying mechanisms and understanding the role of nuclear positioning in myofiber function, we will lay the foundations for future studies to ameliorate or treat muscle disorders as well as other conditions where nucleus positioning may prove to play a role such as cancer. Ámbito científico natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologymedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepathology 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-CG-2013-LS4 - ERC Consolidator Grant - Physiology, Pathophysiology and Endocrinology Convocatoria de propuestas ERC-2013-CoG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-CG - ERC Consolidator Grants Institución de acogida INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES Aportación de la UE € 1 968 000,00 Dirección AVENIDA PROF EGAS MONIZ 1649 028 Lisboa Portugal Ver en el mapa Región Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa Tipo de actividad Research Organisations Contacto administrativo Fausto Lopo De Carvalho (Mr.) Investigador principal Edgar Rodrigues Almeida Gomes (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 INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES Portugal Aportación de la UE € 1 968 000,00 Dirección AVENIDA PROF EGAS MONIZ 1649 028 Lisboa Ver en el mapa Región Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa Tipo de actividad Research Organisations Contacto administrativo Fausto Lopo De Carvalho (Mr.) Investigador principal Edgar Rodrigues Almeida Gomes (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos