Detecting Death and Damage in vivo; Using Drosophila to Understand Innate Immune Cell Priming

The correct regulation of the inflammatory response is critical to maintaining human health. Immune cells operate within a complex environment and are exposed to several different and often competing signals. They respond to damage signals produced at sites of tissue injury, ‘find me’ cues from apoptotic corpses, bacteria at sites of infection as well as attractive signals emanating from pre-malignant cancer cells. How exposure to one of these signals affects an immune cell’s ability to respond to subsequent cues is a largely understudied area of inflammatory cell biology but it is critical if we are to come up with novel therapeutic ways to manipulate inflammatory cell behaviour in the clinic. In this research proposal we will leverage the powerful genetics and live imaging potential of the fruitfly Drosophila to address this process of innate immune priming/memory. We will investigate how innate immune cells sense and respond to the earliest damage signals that trigger inflammation and uncover how exposure to these signals alters subsequent inflammatory behaviour. We will identify novel molecular controllers of the recognition, uptake and processing of apoptotic corpses as well as understand the inflammatory consequences of apoptotic cell uptake both in wounds and within the emerging tumour microenvironment.