Abstract 2315 Supramolecular machines, phase separation, and innate immunity

My talk will focus on structures and functions of the fascinating system of inflammasomes, which are cytosolic supramolecular complexes that activate caspase-1 and other inflammatory caspases. Upon caspase activation, pro-cytokines in the interleukin-1 family and the pore-forming protein GSDMD are proteolytically processed, resulting in cytokine maturation, and formation of large transmembrane GSDMD pores to release cytokines and to induce the lytic cell death pyroptosis. The inflammasome system offers a variety of proteins that oligomerizes, often as peripheral or integral transmembrane proteins, to drive enzymatic chemistry or other cellular processes. At least sometimes, phase separation is preceded to increase the local concentration to promote the supramolecular complex assembly, and the resulting chemistry. We use a combination of biochemistry, cryo-electron microscopy, cellular imaging and inflammasome assays to elucidate the structures and functions of inflammasomes.