Drosophila as a model to study Immune Cell Signal Integration in vivo. (360G-Wellcome-107940_Z_15_Z)

Immune cells live in a complex environment and are constantly bombarded by multiple and often competing signals including wound induced damage signals, apoptotic corpses, and bacteria at sites of infection. To respond efficiently to any one of these cues it is not sufficient for these cells to simply possess the molecular machinery that allows detection of that cue; rather they must integrate the different signals and decide whether to prioritise one over another. We know little about how immune cells achieve this signal integration in vivo but this is key information if we are to design therapeutics to manipulate the decisions made by immune cells such that we can withdraw them from places where they are causing damage and direct them to places where they are needed. Using Drosophila as a model system to study immune cell migration my lab has demonstrated that embryonic macrophages actively migrate towards wounds as well as towards bacteria and apoptotic corpses in vivo. The aim of this application for fellowship renewal is to study how signal integration is achieved within a macrophage in vivo. How do these cells detect the early inflammatory cues coming from a wound? How do the same cells detect and engulf apoptotic corpses and bacteria in vivo and how are these signals integrated with inflammatory damage signals? We also want to understand how exposure to a given cue can prime a cells ability to respond to a subsequent signal and how this innate immune memory is operat ing in vivo.