The long-term goal of the California NanoSystems Institute (CNSI) at the University of California at Los Angeles (UCLA) is to create an enabling and cross-disciplinary environment for cutting-edge nanobiology and biomedical research. As an integral part of this goal, the Electron Imaging Center for Nanomachines (EICN) is established to meet the pressing need of advanced imaging techniques for visualizing macromolecular machineries at the nanometer scale and for the understanding of their mechanisms of action. This high-end shared instrumentation proposal seeks 50% of the funds ($1.6M) needed for the purchase of a SOOkV field emission gun electron microscope for EICN to augment our on-going three- dimensional (3D) structural studies of a broad range of nanomachineries, organelles, viruses and bacterial cells by electron cryomicroscopy (cryoEM) and tomography (ET). The critical need for a user-friendly, high- resolution, tomography-capable electron cryomicroscopy instrument is justified at multiple levels: The high-resolution electron microscope will provide essential instrumentation for over a dozen major users with NIH-funded research projects that require structure determinations either at subnanometer resolution by cryoEM or at molecular resolution by cryoET. Currently, there is no working cryoEM instrument on the UCLA campus. The cryoET-capable electron cryomicroscope in the neighboring Pasadena area at Caltech is not accessible to UCLA faculty members due to already full-capacity operation by local users there. Therefore, UCLA-based research would be greatly enhanced by the acquisition of the high-end electron cryomicroscope described in the application. High-resolution electron imaging will become an integral part of the very strong structural biology research community already established at UCLA. The new high-end EM instrumentation, together with the well-established X-ray crystallography, high-resolution NMR spectrometry, and the molecular modeling expertise will provide a valuable resource for faculty members who are eager to expand the scope of their current biomedical and nanobiology research projects to include cryoEM and cryoET. The new instrument will also meet a critical requirement of high-resolution data for pushing the envelope of cryoEM reconstruction to near atomic resolution. The diverse biological structures with their highly varied architectures offer a fertile source of data for developing and refining the methodology of high-resolution cryoEM, which will not only benefit our efforts but also the general electron imaging community at large. The identification often secondary/minor users with active federal funding shows that there is major interest across multiple departments/institutes among the colleges of natural sciences and engineering, as well as the UCLA medical school that may greatly benefit from the acquisition of the high-end instrument. ? ? ?
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