Obiettivo Mammalian Target Of Rapamycin (mTOR) is an evolutionary conserved protein kinase that integrates signals from growth factors, nutrients and cellular energy status to regulate cell proliferation, survival, growth and metabolism. mTOR functions have been inferred so far by employing rapamycin, an inhibitor that has therapeutical uses as immunosuppressive and anti cancer agent. However rapamycin is not a general mTOR inhibitor because mTOR is part of at least two distinct multiprotein complexes, one of which is rapamycin insensitive. Thus genetic approaches are needed to study the full spectrum of mTOR functions on growth and metabolism. We analyse mouse lines carrying inactivating mutations in the mTOR signaling pathway. The muscle specific mTOR knockout mice show a dramatic phenotype, as they develop a severe muscular dystrophy providing an animal model of myopathy. These preliminary data indicate a novel link between mTOR signaling deregulation and the development of muscular dystrophy. In addition we have demonstrated that the inactivation of the mTOR substrate S6 kinase 1 (S6K1) is sufficient to trigger muscle atrophy. Our future research aims at identifying the causes of these dystrophic and atrophic phenotypes in mammalian tissues. In collaboration with the Medical Genetics department at the Necker Hospital we are setting up a functional screening of muscle samples from myopathic patients to search for mutations in the mTOR pathways. We will establish primary myoblast cultures from muscle biopsies and evaluate the activities of the distinct mTOR effectors. This rapid analysis should restrict the number of candidate alleles to be sequenced. We predict that defects in the mTOR pathway should underlie a broad range of orphan myopathy diseases, potentially opening new strategies for diagnosis and therapy of skeletal muscle pathologies. Finally we will use gain of function mutants and in vivo gene therapy to address the role of this pathway in cancer progression. Campo scientifico medical and health sciencesbasic medicineneurologymuscular dystrophiesmedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinemedical genetics Parole chiave Cancer Cell growth Growth factors Myopathy Nutrition 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-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Invito a presentare proposte ERC-2007-StG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Contributo UE € 831 200,00 Indirizzo RUE DE TOLBIAC 101 75654 Paris Francia Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Contatto amministrativo Nicolas Jeanjean (Mr.) Ricercatore principale Mario Pende (Dr.) 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 INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Francia Contributo UE € 831 200,00 Indirizzo RUE DE TOLBIAC 101 75654 Paris Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Contatto amministrativo Nicolas Jeanjean (Mr.) Ricercatore principale Mario Pende (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato