NIEHS Cryo-EM Core Facility

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The NIEHS Cryo-EM Core continues to lead the deployment and to promote the adoption of techniques in cryo-electron microscopy in the region. Over a dozen peer reviewed articles in high impact journals during FY2022 are a clear indication. The Core has played an important role in the intramural response to the COVID-19 pandemic with four peer reviewed publications describing potential pharmacological targets or reagents against SARS-CoV-2 (Hong et al. PNAS 2022, Fu et al, PloS One 2022, Frazier et al. Nucleic Acids Res. 2022, Frazier et al. Nucleic Acids Res. 2021 and Pillon et al. Nat. Commun.). Many collaborations have led to important contributions to the understanding of structural underpinnings of disease and therapy. These disease relevant structures solved at the Core involve mitochondrial genetic disease (Riccio et al. PNAS), Parkinson and dementia ( Dasari et al., Biochemistry 2022), anticancer drug delivery systems (Saha et al Nano Lett. 2022), antibacterial resistance (Travis et al. Nat. Commun. 2022). Other structures are involved in fundamental biological processes such as pain, cold and heat sensing (Kwon Nat Struct Mol Biol. 2021), metabolic pathways (Klemm et al. J Biol Chem.), and responses to cellular stress (Simoes et al. Cell Rep. 2022, Kumar et al. Nature 2022). The Core benefits from a close collaboration with the Molecular Microscopy Group on the development of methods that enhance our technical capabilities. These include deployment of in house engineered robotic equipment for sample deposition and time resolved structure determination, improved and accelerated methods for data collection, and software for in-line processing and assessment of data. This year we expanded our capabilities by deploying a 300 KeV cryo-electron microscope acquired in collaboration with NIA, NIBIB, NIDA and NCATs. This state-of-the-art instrument will provide access to high-throughput and high-resolution data collection for single particle cryo-EM to the collaborating institutes and to others at the IRP via the NIH Cryo-EM Consortium. We are also completing the deployment of a cryogenic focused ion beam scanning electron microscope (cryo-FIBSEM). This instrument will allow us to delve into the cell to solve the structure of macromolecular complexes in situ.