High content analysis of inflammasome activation (360G-Wellcome-097425_Z_11_Z)

Epithelial and innate immune cells have evolved complex systems for sensing and responding to a multitude of virulence factors and danger signals. Recognition of a diverse range of microbial, stress and damage signals by cytosolic multiprotein complexes called inflammasomes results in activation ofcaspase-1, which subsequently induces secretion of potent pro-inflammatory cytokines IL-1ß and IL-18 and a form of inflammatory cell death called pyroptosis. Inflammasome-mediated processes are important during microbial infections and also in regulating both metabolic processes and mucosal immune responses. Recent evidence links the cellular cytoskeleton that spatially and temporally organizes host immune responses, to inflammasome activation and regulation. Here, the involvement of cytoskeleton in the regulation of inflammasome signaling will be studied in NLRP1 and NLRP3 inflammasome activation. We will perform a microscopy-based high throughput RNA interference screen in cultured human THP-1 cells where genes connected to thecytoskeletal network are knocked out and the effect on inflammasome activation