Phagocytic cells, such as macrophages and microglia, are crucial for internalising and clearing extracellular targets, including dead cells, lipoproteins, synapses, microorganisms, and protein aggregates. The human body clears approximately 200 billion dead cells daily, underscoring the need to maintain the health and functionality of these cells. Ineffective clearance can lead to conditions such as atherosclerosis, neurodegeneration, and macular degeneration.Our research group aims to uncover the molecular mechanisms by which phagocytic cells process and manage these materials throughout their lifespan, which can span from months to years. Phagocytosed materials are enclosed in phagosomes that fuse with lysosomes to form degradative phagolysosomes. After the degradation of materials, the resulting molecules must be extruded from these organelles and either integrated into cellular metabolism or disposed of via paracellular export or detoxification. These processes are critical, as demonstrated by lysosomal storage disorders (LSD), where improper export of catabolites disrupts cellular function.Despite its significance, the mechanisms and dynamics of phagolysosomal cargo processing are not well understood. This project aims to identify the degradation products of diverse phagocytic targets and determine how they are mobilised and sorted within the cell to sustain phagolysosomal function and overall cellular health. We will use a multidisciplinary approach, integrating high-throughput CRISPR-based genetic screening, advanced imaging techniques, cell physiology assays, and phagolysosomal purification methods with mass spectrometry.