Dr. McNulty’s group is interested in understanding the structure, mechanism, and pathogenesis of macromolecular complexes that are key mediators of the innate immune response. The NLRP3 inflammasome has been identified as a key immune sensor for tissue damage. Although NLRP3 inflammasome assembly and activation leads to the production of inflammatory messengers (called cytokines) that alert the host immune system to initiate inflammatory responses, its dysregulation often results in overt disease due to uncontrolled inflammation. Unfortunately, exposure to numerous natural and manmade infectious agents induce NLRP3 inflammasome activation that in turn initiates an undesirable inflammatory response, thereby causing pathologies. Activating molecules trigger mitochondrial damage and subsequent release of mitochondrial contents that ultimately activate the NLRP3 inflammasome. We use cutting-edge biophysical tools such as cryo-electron microscopy coupled to macrophage culture and stimulation assays to probe molecular determinants of recognition and activation of innate immune macromolecular complexes.