Understanding how cytokine regulation contributes to inflammatory disease.

Inflammation is the response of the body to danger (i.e infection or tissue damage) and is a key immune process linked to a broad range of diseases including diabetes, atherosclerosis and cancer. Central to inflammation is the molecular signals that are triggered upon danger and that spread the inflammatory process. Understanding how these signals mediate cell communication during the first steps of inflammation is essential to develop new therapies for inflammatory pathologies.

Two key signals involved in this process are the potent pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Both cytokines, despite having very different effects during the inflammatory response, are activated and released following the assembly of the same macromolecular complex called the inflammasome. Previous work in our lab has shown that post-translational modifications regulate the activity of the inflammasome and IL-1B. However, and despite extensive research in this area, the molecular mechanisms that govern the regulation of IL-18 and its physiological antagonist IL-18binding protein (IL-18BP) at the transcriptional and post-transcriptional level remain poorly characterized.

The main aim of this project is to understand the regulation of IL-18 during inflammatory responses. The candidate will investigate different aspects of the regulation of this cytokine, during different inflammatory conditions using both vivo and in vitro models. You will contribute to this emerging field by building on actual knowledge to understand new mechanisms that contribute to IL-18 mediated inflammatory disease.