Role of Chromatin-Associated Proteins in Inflammation

Regulation of the immune system is key to mount effective responses while avoiding excessive collateral damage. Dynamic chromatin modifications are increasingly appreciated to represent an integral layer of such immunoregulation which, if dysfunctional, may result in inflammatory diseases. Here we propose to study chromatin-related proteins in the context of the innate immune response. We previously demonstrated that SETDB2 regulates the expression of certain inflammatory genes and is involved in the pathogenesis of influenza virus - mediated bacterial superinfection in mice. In this project we propose molecular biology, transcriptional and chromatin-wide investigations in vitro to study their respective molecular functions. This will be complemented by mouse models to investigate the role of SETDB2 and related proteins in inflammation in vivo as well as by human cell culture systems. Taken altogether, I envision that our integrative approach will enable us to uncover novel molecular mechanisms at the interface of chromatin biology and immunology. This in turn may result in an in-depth molecular understanding of infectious and sterile inflammatory diseases that could open new therapeutic avenues.