The core inflammasome as a model for caspase activation (2018-2022)

This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. We propose the speck is a terminal stage, after the major enzymatic activity is over. We will purify smaller early stage inflammasome complexes, for structural analysis. The outcome will be a clearer understanding of processes of caspase activation and inflammasome formation. This will improve our understanding of processes of cell death and innate immunity, and train students in cutting edge techniques.