Objective 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. Fields of science natural sciencesphysical sciencesopticsmicroscopymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicineneurologyparkinsonnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesphysical sciencesopticsspectroscopy Keywords Cellular Structural Biology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2014 - ERC Consolidator Grant Call for proposal ERC-2014-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator WEIZMANN INSTITUTE OF SCIENCE Net EU contribution € 1 143 821,37 Address Herzl street 234 7610001 Rehovot Israel See on map 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 Other funding € 0,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all WEIZMANN INSTITUTE OF SCIENCE Israel Net EU contribution € 1 143 821,37 Address Herzl street 234 7610001 Rehovot See on map 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 Other funding € 0,00 FORSCHUNGSVERBUND BERLIN EV Participation ended Germany Net EU contribution € 852 678,63 Address Rudower chaussee 17 12489 Berlin See on map Region Berlin Berlin Berlin 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 Other funding € 0,00
