Cel The emergence of hepatocellular carcinoma (HCC) has prompted a search for a thorough understanding of the biology of one of its major causative agents, the hepatitis C virus (HCV). Half of genotype 1 patients, the most numerous in Europe, do not respond to treatment, putting them at risk for cirrhosis and HCC. HCV particles acquire via budding and encapsidation cellular proteins. There is mounting evidence on several viral species that virion-bound proteins are prone to be involved either at the replication, budding/egress or entry/release steps of the viral cycle. Identifying such targets may yield ideal candidates for gaining insight on the dependence of HCV upon a restricted subset of host proteins, therefore providing refined sets of genetically stable targets for therapy. This project’s goals are to set up adequate conditions for robust and reproducible purification of HCV virions in clinical samples, followed by the identification of their HCV-bound host proteins and the characterization of their functions. Proteomics profiling of HCV particles purified from clinical samples will be overlaid with proteins identified and characterized in cell culture-grown HCV particles during my post-doctoral training, using clinical biomarker discovery grade criteria. Targets identified in both samples sets will be subjected to in vitro investigations using HCV-replicating cells. Conventional biochemical and imaging methods will be used in order to: (i) ascertain their physical association with HCV virions; (ii) define the modalities of their interaction with HCV proteins; (iii) decipher the topology and subcellular localization of their association with HCV proteins and virions; (iv) quantitatively assess their functional involvement in particle budding, egress or secretion and infectivity. A candidate that yielded satisfactory results in these experiments will be disclosed and further investigated at the level of structural biology, in collaborative research programs. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesRNA viruseshepatitis Cmedical and health sciencesclinical medicinehepatologynatural sciencesbiological sciencesmolecular biologystructural biology Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-2009-RG Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IRG - International Re-integration Grants (IRG) Koordynator INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Wkład UE € 100 000,00 Adres RUE DE TOLBIAC 101 75654 Paris Francja Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Research Organisations Kontakt administracyjny Dominique Pella (Mr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
