CRC TRR 332 - B07: Deciphering the structural code of neutrophil metabolism and function

Basic data for this project

Description

Neutrophils are characterized by a complex intracellular architecture encompassing mitochondria, endoplasmic reticulum, Golgi apparatus, specialized granules and a multilobed nucleus. We are beginning 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 systems organellome pipeline revealing synchronized organelle dynamics mount an "organellome response" that drives immune function. Here, we extend these principles to neutrophils by creating a tailored platform integrating multispectral imaging, AI-driven segmentation and computational modelling to extract organellome features, generate organelle-specific machine-learning representations, map signatures across subsets and activation states, and link them to functional outcomes via metabolomic and proteomic analyses. This strategy produces a high-resolution atlas of neutrophil organelle dynamics, illuminating how organellome composition underlies functional diversity and revealing targets for precision modulation of neutrophil activity in health and disease.