Obiettivo 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. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteins Parole chiave SUMO SUMOylation synaptic receptors neurodegeneration transmission synaptic Programma(i) 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) Argomento(i) ERC-AG-LS5 - ERC Advanced Grant - Neurosciences and neural disorders Invito a presentare proposte ERC-2008-AdG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-AG - ERC Advanced Grant Istituzione ospitante UNIVERSITY OF BRISTOL Contributo UE € 2 148 871,00 Indirizzo BEACON HOUSE QUEENS ROAD BS8 1QU Bristol Regno Unito Mostra sulla mappa Regione South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Rachel Woodford (Ms.) Ricercatore principale Jeremy Martin Henley (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto UNIVERSITY OF BRISTOL Regno Unito Contributo UE € 2 148 871,00 Indirizzo BEACON HOUSE QUEENS ROAD BS8 1QU Bristol Mostra sulla mappa Regione South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Rachel Woodford (Ms.) Ricercatore principale Jeremy Martin Henley (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato