Detecting Death and Damage; Understanding Inflammatory Cell Migration in vivo

A critical early wound response is the recruitment of inflammatory cells drawn by danger cues released by the damaged tissue.  Hydrogen peroxide has been identified as the earliest wound attractant in Drosophila and Zebrafish and we have shown using fly embryos that laser wounding triggers an instantaneous calcium flash in the epithelium which in turn activates the NADPH oxidase DUOX to generate Hydrogen Peroxide.  As a consequence of hydrogen peroxide production, macrophages (hemocytes) within the fly embryo rapidly migrate toward the wound site powered by the formation of dynamic actin-rich lamellipodia.  We use live imaging to understand the mechanism by which inflammatory cells are able to detect H₂O₂ and generate the dynamic actin-rich structures necessary for their migration.  We are particularly interested in how immune cells are able to prioritise competing cues such as wound induced damage signals and ‘eat me’ cues from apoptotic corpses and how exposure to one of these signals influences the cells ability to respond to subsequent cues.