Objetivo Synaptic protein SUMOylation is a completely new and exciting field of investigation. This application will investigate the roles of SUMOylation in normal and pathological synaptic transmission. The functional and pathophysiological implications for synaptic protein SUMOylation are far-reaching. SUMOylation has already been implicated in a diverse array of synaptopathies. Therefore, better understanding of the regulation and consequences of synaptic SUMOylation is of fundamental importance. The starting hypothesis is that targeted SUMOylation of pre- and postsynaptic proteins regulates synaptic transmission and can be neuroprotective through the reduction of excitotoxicity. The main proposal objectives are to: 1) Identify and functionally characterise novel synaptic SUMOylated substrates. 2) Define how SUMOylation regulates presynaptic neurotransmitter release. 3) Determine the activity-dependence of SUMO and SUMO specific protease (SENP) trafficking to synapses. 4) Elucidate the role of SUMOylation in regulating protein protein interactions at synapses. 5) Define the roles of synaptic protein SUMOylation in ischaemia. These ambitious objectives directly address important challenges at the frontier of our current knowledge of the molecular mechanisms regulating synaptic function and will open up new avenues for future basic and translational research. Novel tools and techniques will be used to test my hypotheses by identifying which synaptic proteins are SUMOylated and investigating the underlying mechanisms and downstream effects of SUMOylation in both normal neurones and in in vitro neuropathological models. My group is uniquely qualified to undertake this work because of our extensive directly relevant expertise, proven track record, library of unique tools and wealth of preliminary evidence demonstrating the viability of the experiments proposed. If funded, I believe this work will represent a novel, innovative and highly productive ERC investment. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteins Palabras clave SUMO SUMOylation synaptic receptors neurodegeneration transmission synaptic 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-LS5 - ERC Advanced Grant - Neurosciences and neural disorders Convocatoria de propuestas ERC-2008-AdG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida UNIVERSITY OF BRISTOL Aportación de la UE € 2 148 871,00 Dirección BEACON HOUSE QUEENS ROAD BS8 1QU Bristol Reino Unido Ver en el mapa Región South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Rachel Woodford (Ms.) Investigador principal Jeremy Martin Henley (Prof.) 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 UNIVERSITY OF BRISTOL Reino Unido Aportación de la UE € 2 148 871,00 Dirección BEACON HOUSE QUEENS ROAD BS8 1QU Bristol Ver en el mapa Región South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Rachel Woodford (Ms.) Investigador principal Jeremy Martin Henley (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
