Objetivo Accumulation of damaged and aggregated proteins is associated with age-related neurodegeneration in Alzheimer’s and Parkinson’s patients. The ubiquitin/proteasome system (UPS) is a major proteolytic route functioning in a cellular network that maintains the proteome during stress and aging. Degradation of damaged proteins is mediated by the 26S proteasome upon attachment of ubiquitin (Ub) proteins (ubiquitylation). Another proteolytic system supporting protein homeostasis (proteostasis) is the autophagy-lysosome pathway that degrades proteins inside activated autophagosomes. An age-related impairment of either of these systems causes enhanced protein aggregation and affects lifespan, suggesting functional overlap and cooperation between UPS and autophagy in stress and aging. Despite the progress made in searching for key substrates that are destined for degradation, the major challenge in the field is to understand how these proteolytic systems are mechanistically coordinated to overcome age-related proteotoxicity. The ultimate goal of the proposed research is to assemble a global picture of stress-induced proteolytic networks critical for aging of multicellular organisms. The tissue-specific regulation of protein degradation pathways will be addressed using the powerful genetic model of Caenorhabditis elegans. The suggested project will systematically analyze: inducible protein degradation pathways (Aim 1), the regulation of UPS and autophagy by microRNAs (miRNAs) (Aim 2), and tissue-specific adaptation of proteolytic networks (Aim 3) in stress response and aging. To this end, comprehensive transcriptome analysis, large-scale genetic screenings combined with deep-sequencing technology, and candidate approaches based on in vivo imaging and degradation assays will be performed. Together, we propose a highly complementary research plan that aims to break new grounds in the understanding of proteolytic networks in aging and disease. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesbasic medicineneurologydementiaalzheimerengineering and technologyelectrical engineering, electronic engineering, information engineeringinformation engineeringtelecommunicationstelecommunications networksmobile networkmedical and health sciencesbasic medicineneurologyparkinsonmedical and health sciencesbasic medicinephysiologyhomeostasis 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-CG-2013-LS3 - ERC Consolidator Grant - Cellular and Developmental Biology Convocatoria de propuestas ERC-2013-CoG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-CG - ERC Consolidator Grants Institución de acogida UNIVERSITAT ZU KOLN Aportación de la UE € 1 992 960,00 Dirección ALBERTUS MAGNUS PLATZ 50931 Koln Alemania Ver en el mapa Región Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Tipo de actividad Higher or Secondary Education Establishments Investigador principal Thorsten Hoppe (Prof.) Contacto administrativo Dorothee Eder (Mrs.) 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 UNIVERSITAT ZU KOLN Alemania Aportación de la UE € 1 992 960,00 Dirección ALBERTUS MAGNUS PLATZ 50931 Koln Ver en el mapa Región Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Tipo de actividad Higher or Secondary Education Establishments Investigador principal Thorsten Hoppe (Prof.) Contacto administrativo Dorothee Eder (Mrs.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
