High-resolution structural analysis of cells and tissues is crucial to a wide variety of projects at the Penn State College of Medicine. Such studies include characterization of changes in cellular junctions in diabetes, altered synaptic structures in disease and gene knockouts, structure of melanosomes, ultrastructural analysis of zebrafush mutants, structural analysis of extracellular matrix and of chromatin, and mechanisms of viral budding. This proposal requests funds to replace our aged and inadequate Philips 400 electron microscope with a new JEOL JEM-1400 instrument. The upgrading of electron microscopy instrumentation will enable to better serve the needs of many funded investigators, of whom 14 are listed as the major users group in this proposal. Although our current instrument has provided many valuable images that have been used in publications and to support grant proposals, its effectiveness is greatly diminished by its substantial down time, complexity of use and lack of key features such as tilt to generate 3D images. Also it is complex to set up and use, which has limited access to the facility manager and a few highly trained individuals. To overcome these problems investigators have been increasingly utilizing the microscopes elsewhere, such as the State College campus (a ninety mile drive) or have been resorting to other techniques that do not have the same resolving power, such as confocal microscopy. In choosing the requested equipment we have consulted extensively with colleagues at other institutions and representatives of both JEOL and Philips. The requested JEOL JEM- 1400 microscope has excellent resolution and good contrast of biological samples, is very user friendly and has excellent digital image capability. The requested instrument will provide crucial support to our major users group's projects, but more importantly will aid the development of new research projects in our larger research community. Many of the projects supported by the requested electron microscope provide the essential intellectual underpinnings of the understanding of many important diseases. As such they are a key step in translating knowledge into better and more efficient health care for everyone. [unreadable] [unreadable] [unreadable]