Acquisition of a JEOL JEM-CRYOARM300

Abstract This proposal is for the purchase of a 300 keV cryogenic-transmission electron microscope (cryoTEM) to be housed in the CryoEM Core at the University of North Carolina at Chapel Hill (UNC-CH). This cryoTEM, the JEOL CRYO Arm 300 II (JEM-3300), will serve as a multi-functional instrument to support high resolution data collection for single particle (SP) cryoEM projects as well as for cryo-electron tomography (cryoET) and micro electron diffraction (microED). Currently, the UNC-CH CryoEM Core houses only a single 200 keV cryoTEM, yet the core still serves over 120 researchers representing 50 research groups. These researchers are located not only at UNC-CH, but also at several nearby universities. The UNC CryoEM Core therefore serves as a regional resource to those without cryoEM access and expertise. The addition of a JEM-3300 is crucial for our core to have the capacity needed to support the already high, and continually growing, demand from our NIH-funded user base. As the UNC-CH core has only a single cryoTEM, we struggle to service all users in a timely fashion, even though our instrument is maximizing its available usage time. Additionally, UNC-CH does not have a 300 keV instrument, a prerequisite for performing high-resolution cryoET. The proposed instrument will therefore both expand our throughput for collection of SP cryoEM data, while also expanding our capabilities to perform cutting-edge cryoET and microED experiments. The JEM-3300 will support scientists studying a wide range of research questions relevant to public health. Some of these questions are fundamental, and address regulation of genomic processes, cell division, and exocytosis. Still others address how the enzymes involved in lipid metabolism affect heart health, study the role of amyloid fibrils in Alzheimer's disease, and address viral exosomes and their causative role in cancer. These research questions are diverse but are united in their reliance on high-resolution structural biology to answer mechanistic questions about cell biology. CryoEM has revolutionized modern structural biology, and the new technology fueling this revolution allows researchers to obtain high-resolution structural insights with unprecedented speed and resolution. These insights will allow us to understand the etiology of multiple diseases and move towards therapeutic solutions.