Defining regulators of cell death and inflammasome activation

Pattern recognition receptors, including Toll-like receptors (TLRs) and NOD-like receptors (NLRs), are key components of the innate immune response. They sense microbial, host derived and environmental danger molecules, and induce inflammatory signalling responses via inflammasomes and other molecular complexes. We recently defined how deficiency in the cell death inhibitory protein XIAP sensitises innate immune cells to TLR-induced NLRP3 inflammasome activation, which may explain why XIAP-deficient patients suffer from autoinflammation (Lawlor KE et al. Nature Comms 2015, Lawlor KE* et al. Cell Reports 2017). The aim of this project is to further define molecules, like XIAP, that regulate this alternative inflammasome pathway. This project offers the opportunity to be trained in a variety of techniques, including cell culture, Western blotting/immunoprecipitation, proteomics, overexpression/CRISPR Cas9 gene editing, flow cytometry, ELISA and qPCR.