Cel 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. Dziedzina nauki nauki przyrodniczenauki biologicznebiochemiabiocząsteczkibiałkaproteomikamedycyna i nauki o zdrowiumedycyna klinicznaneurologiademencjachoroba Alzheimerainżynieria i technologiainżynieria elektryczna, inżynieria elektroniczna, inżynieria informatycznainżynieria informacyjnatelekomunikacjasieć telekomunikacyjnasieć mobilnamedycyna i nauki o zdrowiumedycyna klinicznaneurologiachoroba Parkinsonamedycyna i nauki o zdrowiumedycyna klinicznafizjologiahomeostaza Program(-y) 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) Temat(-y) ERC-CG-2013-LS3 - ERC Consolidator Grant - Cellular and Developmental Biology Zaproszenie do składania wniosków ERC-2013-CoG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-CG - ERC Consolidator Grants Koordynator UNIVERSITAT ZU KOLN Adres Albertus magnus platz 50931 Koln Niemcy Zobacz na mapie Region Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Kierownik naukowy Thorsten Hoppe (Prof.) Kontakt administracyjny Dorothee Eder (Mrs.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Wkład UE Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko UNIVERSITAT ZU KOLN Niemcy Wkład UE € 1 992 960,00 Adres Albertus magnus platz 50931 Koln Zobacz na mapie Region Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Kierownik naukowy Thorsten Hoppe (Prof.) Kontakt administracyjny Dorothee Eder (Mrs.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Środki z innych źródeł Brak danych
