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Zawartość zarchiwizowana w dniu 2024-05-27

The role of NLRP6 sensing in regulation of intestinal host-microbiome interactions

Cel

"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."

Dziedzina nauki (EuroSciVoc)

Program(-y)

Temat(-y)

Zaproszenie do składania wniosków

FP7-PEOPLE-2013-CIG
Zobacz inne projekty w ramach tego zaproszenia

System finansowania

MC-CIG - Support for training and career development of researcher (CIG)

Koordynator

WEIZMANN INSTITUTE OF SCIENCE
Wkład UE
€ 100 000,00
Koszt całkowity
Brak danych