Faculty Advisor

Caitlyn Karver, PhD


Inflammatory caspases are involved in the innate immune response, in which cell damage and microorganism invasion lead to cell death via pyroptosis and the release of chemical signals that produce inflammation. Currently, little is known pertaining to the mechanism of activation for one of the major caspase isoforms, caspase-4, other than its ability to bind LPS and become more active because of it. It has been theorized that caspase-4 agregation occurs through a non-cannonical based pathways in forming its respective complex following binding to LPS. Alternatively, caspase-4 may be activated after binding LPS micelles. Herein, we sought to incorporate lipopollysaccharide (LPS) to previously optimized enzymatic conditions to serve as a potential medium for potential agregration via direct binding or micelle formation as a scaffold. It was predicted that pro-caspase-4 units would bind LPS micelles to form a complex that would activate caspase-4 or the enzyme could bind LPS directly and oligomerize, therby becoming activated. However, enzymatic assays performed with caspase-4 and LPS titrations showed little to no significant change in activity. The lack of change does not validate one mechanism of activation over the other as both mechanisms are seemingly LPS dependent. Further studies of the mechanism, and presence of aggregates will be required