Objectif The gastrointestinal tract hosts the microbiome, one of the highest microbial densities on earth. Diverse host-microbiome interactions influence a multitude of physiological and pathological processes, yet the basic mechanisms regulating host-microbiome interactions remain unknown. Deciphering the codes comprising the host-microbiome communication network and factors initiating loss of homeostasis (termed dysbiosis) will enable the recognition of pathways and signals critically important to initiation and progression of common immune and metabolic disorders. We recently identified the NLRP6 inflammasome as a critical innate immune regulator of colonic microbial ecology, with its disruption resulting in auto-inflammation and tumorigenesis. We will use this unique system, coupled with innovative robotic high-throughput modalities, gnotobiotics, metagenomics and multiple genetically altered mouse models to generalize our studies and decipher the critical principles governing host-microbiome interactions. We will elucidate the host-derived microbiome recognition signaling pathway at its entirety, from its upstream activators to the downstream effector molecules controlling microbial ecology; uncover the principles generating a stable microbiota composition; and develop and apply computational modelling to dissect the general mechanisms disrupting microbiome stability leading to dysbiosis. Using this innovative experimental and computational toolbox we will study the impact of dysbiosis on key components of the metabolic syndrome, and apply our findings to devise the first rational proof-of-concept approach for individualized microbiome-based treatment for these common disorders. At the basic science level, unraveling the principles of host-microbiota interactions will lead to a conceptual leap forward in our understanding of physiology and disease. Concomitantly, it may generate a platform for microbiome-based personalized therapy against common idiopathic illnesses. Champ scientifique natural sciencesbiological sciencesecologynatural sciencesbiological sciencesmicrobiologymedical and health sciencesbasic medicinephysiologyhomeostasis 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-CG-2013-LS6 - ERC Consolidator Grant - Immunity and Infection Appel à propositions ERC-2013-CoG Voir d’autres projets de cet appel Régime de financement ERC-CG - ERC Consolidator Grants Institution d’accueil WEIZMANN INSTITUTE OF SCIENCE Contribution de l’UE € 2 000 000,00 Adresse HERZL STREET 234 7610001 Rehovot Israël Voir sur la carte Type d’activité Higher or Secondary Education Establishments Chercheur principal Eran Elinav (Dr.) Contact administratif Gabi Bernstein (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire WEIZMANN INSTITUTE OF SCIENCE Israël Contribution de l’UE € 2 000 000,00 Adresse HERZL STREET 234 7610001 Rehovot Voir sur la carte Type d’activité Higher or Secondary Education Establishments Chercheur principal Eran Elinav (Dr.) Contact administratif Gabi Bernstein (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée