Objectif Tuberculosis, caused by Mycobacterium tuberculosis is still a major threat to global health. Because the treatment of an infected individual requires more than six months of chemotherapy, compliance is low, which can result in the development of multidrug resistant (MDR-TB) strains. New drugs and new targets are needed to combat MDR-TB. A critical feature of the Mycobacterium tuberculosis bacillus is its ability to survive and even replicate within macrophages, making these host cells an ideal niche for persisting microbes. The goal of our project is to understand the biological mechanisms underlying the persistence of intracellular mycobacteria and to develop novel approaches to eradicate the bacillus from its hiding spot. To this end, we have been undertaking global approaches using visual phenotypic assays (relying on monitoring by automated confocal fluorescence microscopy) of the trafficking and replication of M. tuberculosis inside macrophages. Screening of a small interfering RNA library, a M. tuberculosis transposon mutant library and hundreds of thousands of small chemical molecules has led to the identification of key host and mycobacterial genes involved in the intracellular fate of M. tuberculosis, as well as chemicals able to prevent intracellular bacterial growth. Building on the considerable data generated and on the powerful high throughput / high content (HT/HC) confocal microscopy, our project is to further explore the signalling pathways used specifically by M. tuberculosis. We will focus on the in depth study of bacterial protein effectors belonging to the ESX and PPE families and of the SOCS family member CISH, which promotes intracellular mycobacterial survival. Finally, chemicals that target cellular partners of M. tuberculosis will constitute a new starting point for the development of drugs able to counteract this host response manipulation without directly targeting the pathogen, thereby overcoming the issue of the emergence of MDR-TB. Champ scientifique sciences naturellessciences biologiquesmicrobiologiebactériologiesciences médicales et de la santémédecine cliniquepneumologietuberculosesciences naturellessciences physiquesoptiquemicroscopiemicroscopie confocalesciences naturellessciences biologiquesgénétiqueARNsciences médicales et de la santémédecine fondamentalepharmacologie et pharmacierésistance aux médicamentsrésistance multiple aux médicaments 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) Thème(s) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Appel à propositions ERC-2010-StG_20091118 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Coordinateur INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Adresse Rue de tolbiac 101 75654 Paris France Voir sur la carte Région Ile-de-France Ile-de-France Paris Contact administratif Stève Mbaye (Mr.) Chercheur principal Priscille Marie Monique Brodin (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Contribution de l’UE € 1 982 371,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France Contribution de l’UE € 1 982 371,00 Adresse Rue de tolbiac 101 75654 Paris Voir sur la carte Région Ile-de-France Ile-de-France Paris Contact administratif Stève Mbaye (Mr.) Chercheur principal Priscille Marie Monique Brodin (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window
