Objective 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. Fields of science 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) Topic(s) ERC-CG-2013-LS6 - ERC Consolidator Grant - Immunity and Infection Call for proposal ERC-2013-CoG See other projects for this call Funding Scheme ERC-CG - ERC Consolidator Grants Host institution WEIZMANN INSTITUTE OF SCIENCE EU contribution € 2 000 000,00 Address HERZL STREET 234 7610001 Rehovot Israel See on map Activity type Higher or Secondary Education Establishments Principal investigator Eran Elinav (Dr.) Administrative Contact Gabi Bernstein (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all WEIZMANN INSTITUTE OF SCIENCE Israel EU contribution € 2 000 000,00 Address HERZL STREET 234 7610001 Rehovot See on map Activity type Higher or Secondary Education Establishments Principal investigator Eran Elinav (Dr.) Administrative Contact Gabi Bernstein (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data