A group of 27 NIH funded investigators at UCSD requests funds to purchase a FEI Tecnai G2 Spirit BioTWIN transmission electron microscope (TEM) to continue to meet the ongoing and future demands of a variety of researchers within the Department of Cellular and Molecular Medicine (CMM), within the School of Medicine, and within the Division of Biology at UCSD. The requested TEM has an objective lens configuration optimized for high contrast microscopy of biological samples and is perfectly suited for imaging conventional ultrathin plastic sections, immunogold labeled ultrathin cryosections, and negatively stained samples. The Tecnai system is particularly adaptable to a diverse group of users and a multi-user environment. The Department's current 20 year old instruments are showing clear signs of wear and are plagued by increasing down time due to the age and past usage of the instruments. Future reliability is a major concern, and we are seeking to replace one of the TEMs with a modern, state-of-the-art instrument. Our NIH funded investigators study a variety of projects, ranging from single cell organisms to membrane trafficking, and signaling during vascular remodeling, organogenesis and host bacterial interactions. Their work spans a wide variety of disciplines from cell and molecular biology to immunology, pathology, neuroscience, developmental biology and infectious disease. All have in common the fact that they center on cell biological questions that require ultrastructural analysis and immunolocalization studies. The new TEM will ensure that our group of outstanding investigators have continued and uninterrupted access to the techniques and applications necessary for state-of-the-art research in these fields. The FEI Tecnai G2 Spirit BioTWIN will be located, administered and maintained in the existing CMM Transmission Electron Microscopy Facility -- a shared resource that is utilized regularly by numerous researchers. The new TEM will be included in the existing cost recovery system to ensure partial recovery of funds for salaries, maintenance agreements and supplies.