This application requests funds to purchase a Hitachi Model H-7650 Biological, 120kv, transmission electron microscope (TEM) with a Gatan 11megapixel CCD camera for high resolution imaging of fixed biological samples. This instrument will be a shared resource, located in a well-established, multi-user, light and electron microscopy facility at Stanford University: the Cell Sciences Imaging Facility (http://taltos.stanford.edu). This facility is accessible to Stanford University's entire research community as well as surrounding biotech companies. The requested TEM will support NIH funded projects from nine major users. All members of the user group have extensive experience applying electron microscopy to their NIH funded research projects. These projects investigate a wide range of NIH supported topics, including, 1) development of myelinated axons (Talbot);2) mechano-electrical transduction and microtubule cytoskeleton organization in nematode touch receptor neurons (Goodman);3) development of cell polarity in yeast (Pringle);4) the molecular basis of neuronal migration (McConnell);5) microtubule cytoskeleton organization and regulation (Stearns);6) 3D organization of the bacterial chromosome and replisome (Shapiro);7) molecular mechanisms of viral replication, assembly and egress from infected cells (Arvin);8) cellular and molecular mechanisms of wound healing and skin regeneration (Lorenz);9) elucidation of amyloid formation pathway in Alzheimer's disease (Graef). These studies investigate critical structural questions in a variety of model organisms and human tissues and cover areas of research with implications for diverse aspects of human health and disease, ranging from cancer and viral pathogenesis to understanding the molecular basis of immuno-responses and sensory biology. All require, for ultrastructural study of cellular and subcellular structures and molecular complexes, a basic, reliable 120kv transmission electron microscope with high resolution digital imaging that is most effectively provided by a Hitachi Model H-7650 TEM equipped with a Gatan Inc. Orius SC1000B camera.
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