Objetivo To understand the molecular basis of any biological process, it is critical that one is not only able to visualize and monitor molecular events that underlie this process, but also to possess the tools to manipulate these events in a spatial and temporal fashion both in and out of the cell. The overall objective of this proposal is to apply chemical biology approaches to allow real time monitoring of protein aggregation and to dissect the role of specific disease-associated post-translational modifications, phosphorylation, nitration, and truncation on the structure, aggregation, and biochemical properties of monomeric a-syn in health and disease. To achieve these goals, we plan to use a combination of organic chemistry, molecular biology, proteomics, protein engineering, and semisynthetic strategies to facilitate site-specific introduction of post-translational modifications that can be masked and activated in a controllable manner, both inside and outside living cells. Modified synthetic ±-syn will be introduced into primary neurons and cellular models of synucleinopathies and the consequences of masking or activating specific modifications will be assessed using biochemical, immunofluorescence, and live imaging techniques (Specific Aim 1). The absence of specific molecular probes that allow in vivo monitoring and quantitative measurement of toxic misfolded and aggregation intermediates represents a major impediment to understanding the relationship among protein misfolding, post-translational modification, protein aggregation, neurodegeneration, and cell death in PD and other neurodegenerative disorders. To address this challenge, we plan to develop and characterize novel antibodies that target different species along the amyloid formation pathway of ±-syn (Specific Aim 2). Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural scienceschemical sciencesorganic chemistrynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingmedical and health sciencesbasic medicineneurologyparkinsonnatural sciencesbiological sciencesmolecular biology 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-SG-ID1 - ERC Starting Grant Interdisciplinary Panel Convocatoria de propuestas ERC-2009-StG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Aportación de la UE € 1 495 400,00 Dirección BATIMENT CE 3316 STATION 1 1015 Lausanne Suiza Ver en el mapa Región Schweiz/Suisse/Svizzera Région lémanique Vaud Tipo de actividad Higher or Secondary Education Establishments Investigador principal Hilal Lashuel (Prof.) Contacto administrativo Caroline Vandevyver (Ms.) 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 ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Suiza Aportación de la UE € 1 495 400,00 Dirección BATIMENT CE 3316 STATION 1 1015 Lausanne Ver en el mapa Región Schweiz/Suisse/Svizzera Région lémanique Vaud Tipo de actividad Higher or Secondary Education Establishments Investigador principal Hilal Lashuel (Prof.) Contacto administrativo Caroline Vandevyver (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos