We request funds to purchase a shared FEI Quanta 200 FEG Scanning Electron Microscope (SEM). The instrument will be used to support 5 major projects from NIH-funded investigators as well as provide support to a number of other NIH-funded programs. At present, the only SEM available at Vanderbilt is one maintained by the College of Engineering and used primarily for materials science applications. Use of this instrument has been critical for introducing the use of SEM to Vanderbilt biomedical researchers. However, the most mature projects now require an instrument that is designed and dedicated for their specific biological needs. Five Major Users with immediate, essential and appropriate need for the requested instrument will utilize 80% of total instrument activity. The projects range from analyzing changes in cell morphology resulting from mutated proteins in order to probe the function of those proteins, investigating the mechanism of microbial invasion of mammalian tissue, aiding the development of new methods of visualizing the 3D ultrastructure of cells, and investigating uptake and secretion of lipids. Another 3 projects have an immediate need for some access to SEM (see Other User List). This will utilize an additional 10% of the initial instrument usage. In addition, we know from historical precedent that placing a FEI Quanta FEG SEM dedicated to biomedical research in the established and widely used Cell Imaging Shared Resource (CISR) will also spur the use of this technology by many more NIH-sponsored Vanderbilt researchers. Instrument time for our other instrumentation is used >90% by NIH-funded projects. We expect that the new SEM will match this profile. The CISR is a core laboratory that supplies access to sophisticated microscopy. All Major Users on this application will have access to the instrument and training through the established CISR infrastructure. Usage charges have supported the service contract for the existing microscopes over the last eight years, and we foresee no difficulty in continuing that arrangement for the Quanta 200 FEG SEM. In addition, the CISR staff will identify from existing CISR users those researchers whose projects would benefit from SEM. The Resource has an extensive track record of education, training, and productivity with over 250 lab groups at Vanderbilt University. Over the last 16 years, we have introduced shared access to confocal microscopy, live cell imaging, two-photon excitation, total internal reflection (TIRF) microscopy, fluorescence correlation spectroscopy, deconvolution microscopy and transmission and scanning electron microscopy. Having access to an SEM that is specifically configured for biomedical research and housed within the Vanderbilt University Medical Center's Cell Imaging Shared Resource (CISR) will offer significant advantages for biological research at Vanderbilt and will greatly facilitate the use of SEM by NIH-funded biomedical researchers.