Grant: CIHR Fellowship

NLRP3 inflammasome, a multiprotein complex, plays a critical role in innate immunity, which enables us to fight against pathogens. NLRP3 inflammasome is activated by various stimuli that directly or indirectly related to pathogen invasion. K+ efflux is a common cellular event associated with these stimuli. A protein called Nek7 is required for the inflammasome activation through interacting with NLRP3, a central component of NLRP3 inflammasome. Importantly the interaction is promoted by K+ efflux. Here I propose to study at molecular level how K+ efflux leads to Nek7-mediated NLRP3 activation. Since only activated NLRP3 triggers key inflammatory responses to defend invaded pathogens, it is vital to understand how NLRP3 is activated. The proposed study will yield essential information regarding NLRP3 activation and advance the field of innate immunity. NLRP3 inflammasome links to the pathogenesis of a wide array of inflammatory disorders, such as silicosis, gouty arthritis, atherosclerosis, type 2 diabetes, Alzheimer's and Parkinson's diseases. Understanding the mechanism of NLRP3 activation will also provide basis for designing drugs to target NLRP3 activation process, benefiting human health.