Project Summary The Analytical Imaging Core (Core B) will continue serving the four projects of this Program Project. The long-term goal of this core is to provide support for the needs of the individual projects on image-based procedures, protein analysis and chemical biology. The specific aims of this core are: 1) to provide a comprehensive imaging facility that will assist the investigators in the morphological studies required to analyze the role of age-related changes in autophagy in different cellular and animal models; 2) to work with the members of the individual projects toward the implementations in their experimental settings of methods for protein analysis; and 3) to initiate the development of targeted therapeutics based on modulation of autophagic pathways for testing in the different cellular and animal models used by the projects. The components of the core are: 1) The Imaging unit: That has and will continue providing advice on sample preparation/processing and techniques and procedures for analytical imaging, performing the specialized imaging procedures, and assisting with the interpretation of morphological images; 2) The innovation unit: That explores, tests and implements procedures for protein modification analysis and for the development of chemical modulators of autophagy using structural and chemical biology. The services offered by the core include: a comprehensive array of analytic imaging procedures (direct and indirect immunofluorescence, real time fluorescence microscopy, confocal fluorescence, conventional and cryoelectron microscopy and immunogold), access to the imaging instrumentation, and a stock of common reagents (antibodies, probes and fluorescent dies) for the imaging procedures. The new services available during this period will include tomography, Immunogold/silver enhancement for intact cells labelling, in vivo imaging, protein aggregates islation and development, characterization and distribution of CMA activators. The key personnel are the directors, a dedicated technician, the expert technical staff of the imaging core at Einstein, an expert in chemical medicine and an expert in targeted therapeutics. The directors will supervise all of the activities of the core, offer advice and assist with result interpretation. The technical staff will prepare and process samples for morphological studies and maintain the supplies and reagents required for the core. Relevance: Imaging procedures and protein analysis are essential and common to all four projects in this program as they allow the study of the cellular process of interest in the whole cells or organs. The centralization of the procedures optimizes cost efficiency, guarantees their uniformity and allows for integration of the data obtained by the different groups. The incorporation of a chemical biology component to the core will facilitate development of anti-aging therapeutics based on autophagy modulation.