Objective Neuronal metabolism is emerging as an essential regulator of brain function and its deregulation is a common denominator in neurological disorders entailing intellectual disability and synapse dys-morphogenesis. The autophagy-lysosome system is the major catabolic pathway dedicated to the recycling not only of protein aggregates but also lipids, nucleic acids, polysaccharides and defective or superfluous organelles, among others. Appreciation of the role of autophagic pathways in the healthy and diseased brain continues to expand, as accumulating evidence indicates that proper regulation of autophagy is indispensable for neuronal integrity. At the cellular level, several lines of evidence implicate autophagy in the regulation of synaptic plasticity. However, the synapse-specific substrates of autophagy remain elusive. Similarly, the synaptic defects arising from autophagy impairment have never been thus far systematically addressed, yet they translate into severe behavioural deficiencies, such as compromised memory and cognition, pertinent to disorders of intellectual disability. The present proposal aims to determine how autophagy regulates synaptic plasticity and how its deregulation contributes to synaptic defects. In particular, the objectives aim to: 1) Monitor and characterize the presence of the autophagic machinery in pre- and post-synaptic sites. 2) Identify autophagic substrates residing in synapses and whose turnover via autophagy determines synaptic plasticity. 3) Characterize the synaptic defects and ensuing behavioural deficits arising from impaired autophagy in the hippocampus. 4) Use C. elegans as a model system to address the evolutionary conservation of the synaptic role of autophagy and perform forward genetic screens to reveal novel regulators of autophagy in synapses. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesbiochemistrybiomoleculescarbohydratesmedical and health sciencesbasic medicineneurology Keywords metabolism dendritic spines forward genetic screens Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-STG - ERC Starting Grant Call for proposal ERC-2016-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution UNIVERSITE DE LAUSANNE Net EU contribution € 925 307,19 Address QUARTIER UNIL CENTRE - BATIMENT UNICENTRE 1015 LAUSANNE Switzerland See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 925 307,19 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITE DE LAUSANNE Switzerland Net EU contribution € 925 307,19 Address QUARTIER UNIL CENTRE - BATIMENT UNICENTRE 1015 LAUSANNE See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 925 307,19 IDRYMA TECHNOLOGIAS KAI EREVNAS Participation ended Greece Net EU contribution € 568 442,81 Address N PLASTIRA STR 100 70013 Irakleio See on map Region Νησιά Αιγαίου Κρήτη Ηράκλειο Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 568 442,81
