Investigating non-professional efferocytosis through two new, in vivo models

Apoptotic cell death is fundamental to life – sculpting tissues during development; underpinning homeostatic tissue turnover; and driving repair and regeneration. However, apoptotic corpses must be rapidly engulfed and cleared, a process called efferocytosis, to avoid triggering inflammatory responses which cause disease. Professional phagocytes, such as macrophages, are well known in apoptotic corpse clearance, yet in many tissues non-professional phagocytes also make important contributions to efferocytosis. These non- professionals are largely overlooked and remain poorly understood due to a lack of quality models and tools for their study. To address this, I will develop and define two new, complementary in vivo models of non-professional efferocytosis in the developing fruit fly. Capitalising on Drosophila’s powerful genetic toolkit, which allows live visualisation of apoptosis and efferocytosis, I will characterise cell-level mechanisms employed by these non-professional phagocytes to engulf and process apoptotic corpses. I will then identify conserved features in vertebrate systems. Finally, I will take a tissue-level perspective and investigate the functional contributions and consequences of apoptotic corpse clearance by different phagocyte populations. This will deliver major advances in understanding of non-professional efferocytosis, relevant to development, homeostasis and disease, with the models I establish providing a powerful platform for my future independent research programme.