Cryo Transmission Electron Microscope for Cryo-EM Sample Optimization

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PROJECT SUMMARY/ABSTRACT Cryo-electron microscopy (Cryo-EM) has heralded a resolution revolution in structural biology that has made it possible for high-resolution structures to be determined for targets that have remained recalcitrant to crystallization for decades. Cornell has invested in this future with the purchase of a high-end electron microscope, the Arctica with a K3, allowing researchers an important valuable tool with which to reveal the atomic details of their cryo-frozen biological samples. Unfortunately, we are scheduled to lose our dedicated low-end screening microscope, the Morgagni, sometime in 2021 or possibly 2022. In analyzing our current workflow and needs of the structural biology community at Cornell, we have concluded that the optimal replacement for the Morgagni is a F200Ci microscope capable of both negative stain data collection and cryo-EM imaging. Acquiring such a microscope will improve overall throughput for Cornell scientists and the NIH-funded investigators’ research programs, maximizing the utility of our highest-resolution and most in-demand microscopes which are equipped with accessories crucial for high-resolution data collection: a the K3 direct detector and a BioQuantum Energy Filter. This application requests funds to purchase a versatile cryo-electron microscope ideally capable of negative stain imaging, cryo-sample screening, and micro-electron diffraction (microED). It will serve NIH-funded faculty in five departments across Cornell, all invested in pursing the structure of biomedically relevant and important biological systems related to human health, including membrane receptors, membrane trafficking, nucleic-acid complexes involved in genome organization, and viral structure.