Investigating damage sensing, molecular priming and receptor recycling in Drosophila embryonic macrophages (360G-Wellcome-109065_Z_15_A)

The use of model organisms is key to develop our understanding of dynamic immunological processes. Drosophila melanogaster embryonic macrophages carry out a diverse range of tasks, with many of the relevant molecules having human orthologues. Despite recent advances in immune cell biology, there are still many unknowns in the processes of damage signalling and apoptotic cell clearance, and how these areas link to the recent discovery of macrophage priming. As cell membrane receptors underpin the ultimate functionality of immune cells, their correct trafficking through the endosomal system must be key for the maintenance of macrophage activity. We wish to test some newly uncovered potential candidates in immune cell wound recruitment, as well as searching for priming ligands and observing how disruption to the endosomal system affects immune cell function. The tractable genetics of Drosophila will allow us to investigate potential candidates in both mutant and RNAi knockdown conditions. To do this, we will use in vivo live cell imaging of embryonic macrophages using fluorescent probes driven by the Gal4,UAS system. Live imaging immune cells - particularly their response to laser induced wounds - will enable us to gain a better understanding of the molecular mechanisms that underpin their diverse functions.