Obiettivo Proteolysis affects every protein through limited processing or degradation. Unlike other post−translational modifications, proteolysis is irreversible and occurs intra− and extracellularly. The large number of genetically encoded proteases in man (> 560) illustrates the importance of proteolysis. However, the in vivo substrate profiles of most proteases have remained elusive; presenting a major hurdle to understanding protease function in health and disease.System−wide identification of protease substrates is now enabled by novel proteomic strategies for the quantitative determination of neo N− and C−termini. In this project, proteolytic events and cleavage products are identified and validated in cellular model systems in order to understand how proteolysis contributes to tumor aggressiveness and neurodegeneration.In the area of tumor biology, the paracrine loop between cancer and stroma cells is dissected. Both cell types secrete cytokines and cytokine−modifying proteases; thereby potentiating tumor proliferation and invasiveness. Identification of key cleavage events and key proteases in tumor−stroma interaction unravels the role of proteolysis in cellular communication. In addition, the substrate profile of the stroma−specific, cell−surface protease “Fibroblast activation protein” is determined.In the area of neurodegeneration, this project identifies and validates substrates of the orphan, neuroprotective protease DJ−1. Mutants of DJ−1 are associated with early−onset Parkinsonism. In addition a novel dual−label approach for the monitoring protein−specific degradation rates on a proteome−wide scale is established. This unique strategy examines the relation between a–synuclein aggregation (a hallmark of Parkinson’s disease) and impaired proteome turnover.The combination of novel proteomic techniques with state−of−the−art cell biological approaches is uniquely suited to determine how proteases control cellular fate in tumorigenesis and neurodegeneration. Campo scientifico natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineneurologyparkinson Programma(i) 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) Argomento(i) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Invito a presentare proposte ERC-2011-StG_20101109 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante UNIVERSITAETSKLINIKUM FREIBURG Contributo UE € 1 499 760,00 Indirizzo HUGSTETTER STRASSE 49 79106 Freiburg Germania Mostra sulla mappa Regione Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Oliver Schilling (Dr.) Contatto amministrativo Jürgen Dreyer (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto UNIVERSITAETSKLINIKUM FREIBURG Germania Contributo UE € 1 499 760,00 Indirizzo HUGSTETTER STRASSE 49 79106 Freiburg Mostra sulla mappa Regione Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Oliver Schilling (Dr.) Contatto amministrativo Jürgen Dreyer (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato