Project Area B: Intracellular regulation

Neutrophils are characterized by a complex intracellular architecture encompassing mitochondria, endoplasmic reticulum, Golgi appa-ratus, specialized granules and a multilobed nucleus. We are begin-ning to understand that these organelles contribute to neutrophil function, but insight into how distinct organelle processes cooperate to shape neutrophil fate under varying conditions is limited. To bridge this gap, we developed OrgaPlexing, a macrophage-focused sys-tems organellome pipeline revealing synchronized organelle dynam-ics mount an “organellome response” that drives immune function. Here, we will extend these principles to neutrophils by creating a tai-lored platform integrating multispectral imaging, AI-driven segmenta-tion and computational modelling to (I) extract organellome features, (II) generate organelle-specific machine-learning representations, (III) map signatures across sub-sets and activation states, and (IV) link them to functional outcomes via metabolomic and proteomic analyses. This strategy will produce a high-resolution atlas of neutrophil organelle dynamics, illumi-nating how organellome composition underlies functional diversity and revealing targets for precision modulation of neutrophil activity in health and disease.