Core A: Imaging, Protein Production, and Chemical Biology Core SUMMARY/ABSTRACT The goal of the Imaging, Protein Production, and Chemical Biology Core is to maximize the scientific progress and productivity of PPG investigators by providing essential services and reagents. The core will perform three major functions for the PPG: (1) advanced light and electron microscopy imaging;; (2) protein and antibody production;; and (3) chemical proteomics. All three PPG component projects will utilize at least two core services, and two of the projects will utilize all three. Centralizing these activities within a core will benefit the PPG by increasing productivity and reducing costs. The core will provide full-service scanning and transmission electron microscopy, standard and live-cell confocal fluorescence microscopy, and NanoSIMS imaging. The latter is a mass spectrometry–based imaging modality that makes it possible to create high-resolution images of cells and tissues based solely on their isotopic content. PPG investigators will use NanoSIMS to visualize and quantify the localization and movement of lipids in cells and tissues. PPG investigators will also study new molecules and novel mechanisms regulating lipid transport and signaling, for which few reagents exist. To assist these investigations, the core will produce protein and antibody reagents for PPG studies (e.g., soluble GPIHBP1, stable isotope–labeled ALO-D4, 5D2 Fab fragments). Finally, the core will perform Activity-Based Chemical Proteomics and isotopic Tandem Orthogonal Proteolysis‒Activity-Based Protein Profiling. These state-of-the-art proteomics discovery platforms will be used to identify proteins involved in the intracellular trafficking of HDL- derived cholesterol and the regulation of STING signaling by cholesterol. For the next five years, the core is poised—with the experience, robust protocols, and experienced personnel—to provide vital services to PPG investigators.