Project Summary/Abstract This proposal represents a request from a group of NIH-funded investigators with overlapping imaging needs for funding to acquire a new high-sensitivity CMOS camera to facilitate the visualization of both cellular sand sub- cellular ultrastructure at the nanoscale. The camera will be installed on an existing Transmission Electron Microscope that is already housed in the Washington University Center for Cellular Imaging (WUCCI); an institution-wide shared technology resource based at the School of Medicine. The current camera installed on the TEM in the WUCCI is over 15 years old, is starting to suffer from an increasing number of dead pixels and does not provide the signal-to-noise ratios needed to facilitate the work of the Major and Minor User projects described herein. The AMT NanoSprint15 Mk-II is a new 15 Megapixel scintillated CMOS camera system providing unparalleled signal-to-noise across many different sample types. Thirteen investigators from ten different departments across the Schools of Medicine and Arts & Sciences will make use of this new and improved camera platform to enable a wide-range of research studies aimed at understanding the molecular mechanisms of viral infection, vascular malformation, endocrine dysfunction, neurodegeneration, metabolic homeostasis, axonal regeneration and mechanosensation as well aid in the development of novel nanotherapeutic approaches to treat cancer and inflammatory conditions. The expertise and institutional support for this instrument are exceptional. Dr. James Fitzpatrick, the Scientific Director of WUCCI, and Dr. David Piston, the Chair of Cell Biology & Physiology and head of the WUCCI Advisory Board, are both world-renowned experts in cellular microscopy and their combined leadership brings over 40 years of experience in providing cost- efficient training and support for high quality quantitative light and electron microscopy to a wide range of NIH- funded users. In support of this S10 grant application, the institution will also commit $100,000 ($20,000 per year for five years) to ensure the long-term success of this equipment.