Objectif 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. Champ scientifique sciences naturellessciences biologiquesbiochimiebiomoléculeprotéinesprotéomiquesciences médicales et de la santémédecine fondamentaleneurologiedémencealzheimeringénierie et technologiegénie électrique, génie électronique, génie de l’informationingénierie de l’informationtélécommunicationréseau de télécommunicationsréseau mobilesciences médicales et de la santémédecine fondamentaleneurologieparkinsonsciences médicales et de la santémédecine fondamentalephysiologiehoméostasie Programme(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) Thème(s) ERC-CG-2013-LS3 - ERC Consolidator Grant - Cellular and Developmental Biology Appel à propositions ERC-2013-CoG Voir d’autres projets de cet appel Régime de financement ERC-CG - ERC Consolidator Grants Coordinateur UNIVERSITAT ZU KOLN Adresse Albertus magnus platz 50931 Koln Allemagne Voir sur la carte Région Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Chercheur principal Thorsten Hoppe (Prof.) Contact administratif Dorothee Eder (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Contribution de l’UE Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITAT ZU KOLN Allemagne Contribution de l’UE € 1 992 960,00 Adresse Albertus magnus platz 50931 Koln Voir sur la carte Région Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Chercheur principal Thorsten Hoppe (Prof.) Contact administratif Dorothee Eder (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Autres sources de financement Aucune donnée
