Amanda Mackenzie

Our research focuses on understanding the mechanisms of inflammation and inflammatory disease.

Cell biology of immune cells

My research group is interested in innate immunity including macrophage and microglia inflammatory responses. In particular, we have an interest in molecular signalling pathways, including reactive oxygen species and the role of hypoxic regulation, underlying the activation of the NLRP3 inflammasome and the production of the inflammatory cytokine interleukin 1 (IL-1Beta).

The production of bioactive IL-1Beta is a tightly controlled multi-step process: first IL-1Beta is produced as an inactivate precursor 31 kD pro-IL-1Beta, this is cleaved to produce bioactive 17 kD IL-1Beta and then finally the bioactive IL-1Beta. The processing and cleavage of the IL-1Beta precursor is achieved by caspase-1 activated within a multi-protein complex termed the NLRP3 inflammasome. We have specific interest in the pathways leading to activation of the NLRP3 inflammasome activation in macrophages and microglia.

Sites of inflammation exist under hypoxic conditions where changes in oxygen levels alter the phenotype of cells and the inflammatory response.  The research group is interested in understanding how hypoxia regulates inflammatory responses, in particular inflammasome responses, compared to standard tissue culture conditions.  The Advanced Hypoxic facility was funded by the BBSRC ALERT14 equipment call.

Our research is funded by the EPSRC, BBSRC and the University of Bath.