Events @ Warwick Chemistry

Inflammasomes are multiprotein signalling complexes of the innate immune system, triggered by a range of microbial pathogens and molecules derived from host proteins. Canonical inflammasomes serve as activating scaffolds for pro-caspase-1, which in turn process Gasdermin D (GSDMD) and induces activation of cytokines IL-1b and IL-18. The released N-terminal domain of GSDMD oligomerises at the plasma membrane forming pores that mediate pyroptosis and cytokine secretion. Therefore, GSDMD is a valuable drug target for inflammatory diseases. Native mass spectrometry (MS) has emerged as a powerful analytical technique to study proteins and their non-covalent complexes. This includes interactions with small-molecule drugs. Given the speed and the low amount of sample needed, native MS could bring tremendous advantages in understanding protein-drug interactions in a high-throughput manner. We have utilised native MS to capture GSDMD-Caspase-1 interactions, known to be implicated in inflammatory cell death. Moreover, we have developed a high-throughput native MS screening platform, which allows screening of over 50k small-molecule compounds in less than 7h, demonstrating the utilization of native MS as a high-throughput screening platform in drug discovery.