Objectif "Nucleotide-binding domain, leucine-rich repeat-containing (NLR) proteins have emerged as central regulators of immunity and inflammation. Several NLRs form cytosolic multi-protein complexes termed inflammasomes in response to pathogen and damage- associated molecular patterns. We recently identified the NLRP6 inflammasome as a critical innate immune regulator of the intestinal microbiome, a diverse ecosystem whose poorly understood interactions with the host influence a multitude of physiological and pathological processes. We found that NLRP6 inflammasome disruption results in dramatic alterations in microbiome composition & function, in turn leading to auto-inflammation and a propensity to the development of metabolic syndrome. However, the basic mechanisms governing NLRP6 activation & regulation of host-microbiome interactions remain unknown. Using the NLRP6 system as a proof-of-principle model, and innovative robotic high-throughput modalities, gnotobiotics, metagenomics and multiple genetically altered mouse models we will decipher the codes comprising the host-microbiome communication network and factors initiating loss of homeostasis (dysbiosis). As part of our studies, we will (A) elucidate the host-derived microbiome recognition signaling pathway at its entirety, from its upstream activators to the downstream effector molecules controlling microbial ecology; (B) decipher the cell-specific mechanisms of NLRP6 regulation of the intestinal crypt niche; and (C) uncover mechanisms by which the innate immune arm regulates the composition and function of the gut commensal eco-system in health and disease. From a research perspective, deciphering the principles of NLRP6 signaling and its regulatory effects on host-microbiota interactions in health and disease will lead to a conceptual leap forward in our understanding of physiology and pathology. Concomitantly, it may generate a platform for microbiome-based personalized therapy against common idiopathic diseases." Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepathologynatural sciencesbiological sciencesecologyecosystemsnatural sciencesbiological sciencesmicrobiologymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2013-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur WEIZMANN INSTITUTE OF SCIENCE Contribution de l’UE € 100 000,00 Adresse HERZL STREET 234 7610001 Rehovot Israël Voir sur la carte Type d’activité Higher or Secondary Education Establishments Contact administratif Gabi Bernstein (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée