A diverse group of 9 major and 8 minor users who are well funded NIH investigators, within the Johns Hopkins School of Arts &Sciences, Whiting School of Engineering, and the JHMI School of Medicine, request funds to purchase an FEI Tecnai F20 TWIN 200kV transmission electron microscope (TEM) with a Falcon II direct detection camera. This new state-of-the-art TEM will be housed in the Hopkins Integrated Imaging Center (www.jhu.edu/IIC) that is the only TEM facility on the Hopkins'Homewood campus;and is well utilized by the Hopkins-wide research community. It will replace a 30 year old Philips EM 420 for which service and day-to-day reliability has become critically dubious (see letter from John Fike, East Regional Service Manager, FEI in Appendix A);and perfectly complement an existing Tecnai 12. If funded, the Tecnai F20 will become the primary TEM platform for cryoelectron microscopy and low dose applications at Hopkins. Its 200kV capability, FEG, and Falcon II direct detection camera will add upgraded capabilities in cryo and molecular TEM, that are not currently present, astonishingly, anywhere at Hopkins;and it will free up our existing T12 for use in more conventional, routine TEM applications. Our investigators, all well-funded through the NIH, work on a host of basic cell biological, biochemical, and biomolecular related questions including, though not limited to: HIV structure and function, HSV assembly and maturation;DNA regulation and chromosome suprastructure, membrane organization and dynamics;endosome/lysosome dynamics;membrane trafficking;trafficking of polymeric gene carriers;sialic acid display and cell adhesion;and mechanisms of endocytosis. The new Tecnai F20 will ensure that our diverse group of investigators have continued and uninterrupted access to a TEM optimized for many disparate applications;as well as allowing for future growth in more exotic structural applications of cryoTEM and single particle analysis. The Tecnai F20 will be conveniently located, administered, and maintained, in the Biology Department's soon to be renovated Integrated Imaging Center (IIC), a Homewood campus/Hopkins-wide microscopy resource that is utilized regularly by multiple schools and departments comprising >150 laboratories and >400 users. The IIC is a Hopkins'Homewood campus core microscopy resource associated with the Institute for NanoBioTechnology (INBT);and the newly established Engineering in Oncology Center. It is jointly supported by the Krieger School of Arts and Sciences and the Whiting School of Engineering;and is utilized regularly by multiple schools/departments The new system will be incorporated into the IIC's existing recharge system to ensure recovery of funds for supplies and maintenance;and it will be made freely available to all interested users Hopkins-wide through our convenient IIC web-scheduler and smart phone app.