Objective 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. Fields of science 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 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) Topic(s) ERC-CG-2013-LS3 - ERC Consolidator Grant - Cellular and Developmental Biology Call for proposal ERC-2013-CoG See other projects for this call Funding Scheme ERC-CG - ERC Consolidator Grants Coordinator UNIVERSITAT ZU KOLN Address Albertus magnus platz 50931 Koln Germany See on map Region Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Principal investigator Thorsten Hoppe (Prof.) Administrative Contact Dorothee Eder (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 1 992 960,00 Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITAT ZU KOLN Germany EU contribution € 1 992 960,00 Address Albertus magnus platz 50931 Koln See on map Region Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Principal investigator Thorsten Hoppe (Prof.) Administrative Contact Dorothee Eder (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window
