Obiettivo Intracellular aggregation of the human amyloid protein alpha-synuclein is causally involved in Parkinson’s disease, a debilitating neurodegenerative disorder. The goal of this project is to combine low-resolution, fluorescence-imaging methods with high-resolution in-cell NMR and EPR spectroscopy techniques to derive macroscopic and microscopic insights into alpha-synuclein aggregate structures directly in neuronal cells. To achieve this goal, we will employ different sets of cultured neurons and investigate intracellular alpha-synuclein aggregation under defined conditions of mitochondrial dysfunction and cellular oxidative stress, two of the most common denominators of the disease. Importantly, we will also establish a human stem cell model for studying alpha-synuclein aggregation with high-resolution in-cell NMR and EPR methods, by using induced pluripotent stem cell (iPSC) derived dopaminergic neurons from Parkinson’s disease patients and control individuals. Results from this study will provide novel insights into the native mechanisms of intracellular aggregate formation and ultimately enable novel pharmacological approaches for therapeutic intervention. Campo scientifico natural sciencesphysical sciencesopticsmicroscopymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicineneurologyparkinsonnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesphysical sciencesopticsspectroscopy Parole chiave Cellular Structural Biology Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-CoG-2014 - ERC Consolidator Grant Invito a presentare proposte ERC-2014-CoG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Istituzione ospitante WEIZMANN INSTITUTE OF SCIENCE Contribution nette de l'UE € 1 143 821,37 Indirizzo HERZL STREET 234 7610001 Rehovot Israele Mostra sulla mappa Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 143 821,37 Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto WEIZMANN INSTITUTE OF SCIENCE Israele Contribution nette de l'UE € 1 143 821,37 Indirizzo HERZL STREET 234 7610001 Rehovot Mostra sulla mappa Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 143 821,37 FORSCHUNGSVERBUND BERLIN EV Partecipazione conclusa Germania Contribution nette de l'UE € 852 678,63 Indirizzo RUDOWER CHAUSSEE 17 12489 Berlin Mostra sulla mappa Regione Berlin Berlin Berlin Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 852 678,63