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| National Cryo-EM Facility | |
|---|---|
| Name | National Cryo-EM Facility |
| Established | 2017 |
| Location | United States |
| Type | Research infrastructure |
| Director | Carla M. Johnson |
| Affiliation | National Institutes of Health, National Institute of General Medical Sciences |
| Equipment | Titan Krios, K3 camera, Vitrobot, Glacios |
National Cryo-EM Facility is a centralized imaging center providing high-resolution cryogenic electron microscopy services and training to researchers across the United States, supporting structural biology, virology, and drug discovery. The Facility combines advanced instrumentation, computational pipelines, and user-access programs to accelerate projects from single-particle analysis to cryo-electron tomography, complementing national initiatives in biomedical imaging and structural genomics. It operates within a broader ecosystem that includes major research institutions and agencies such as the National Institutes of Health, Howard Hughes Medical Institute, and Lawrence Berkeley National Laboratory.
The Facility offers access to high-end microscopes like the Thermo Fisher Scientific Titan Krios and accessories including direct electron detectors (e.g., Gatan K3) and automated vitrification devices such as the FEI Vitrobot; it pairs hardware with computational resources inspired by pipelines at EMBL, Diamond Light Source, European Molecular Biology Laboratory, and Janelia Research Campus. Users from universities, biotech firms, and government laboratories including Massachusetts Institute of Technology, Stanford University, Harvard University, University of California, San Francisco, Columbia University, Johns Hopkins University, and Yale University rely on the Facility for projects that intersect work by investigators who have published in venues tied to Cold Spring Harbor Laboratory, Nature, Science, Cell, and Proceedings of the National Academy of Sciences. The Facility engages with consortia including the Structural Biology Data Grid and initiatives connected to NIH Office of Strategic Coordination.
Founded in response to growing demand for cryo-electron microscopy following breakthroughs associated with pioneers like Richard Henderson, Jacques Dubochet, and Joachim Frank, the Facility's development paralleled milestones such as the 2017 Nobel Prize in Chemistry. Early planning involved partnerships with the National Center for Cryo-EM Access and Training model, drawing lessons from facilities at University of Oxford, Max Planck Institute for Biophysical Chemistry, and MRC Laboratory of Molecular Biology. Initial funding rounds incorporated awards from National Institute of General Medical Sciences, technology investments influenced by vendors including Thermo Fisher Scientific and Gatan, Inc., and collaborations with philanthropic entities similar to those supporting HHMI initiatives. Expansion phases aligned with community workshops modeled after meetings at Gordon Research Conferences and training symposia hosted by Cold Spring Harbor Laboratory.
The Facility houses multiple high-end microscopes: at least one Titan Krios for high-throughput single-particle analysis, a mid-range Glacios for screening, and specialized stages for cryo-electron tomography used in structural virology studies paralleling work at Scripps Research and Rockefeller University. Ancillary equipment includes automated plunge freezers inspired by the Vitrobot design, cryo-transfer systems used in laboratories such as Argonne National Laboratory, and sample-preparation tools employed by groups at EMBL Heidelberg. Computational infrastructure supports motion correction, CTF estimation, and 3D reconstruction using software stacks comparable to RELION, cryoSPARC, Warp, cisTEM, and visualization tools like UCSF Chimera and PyMOL; data management borrows architectures similar to OMERO and archival practices at Protein Data Bank centers.
Research programs span single-particle reconstruction of macromolecular complexes, cryo-electron tomography of cellular architecture, and integrative structural biology combining cryo-EM with cryo-focused ion beam milling workflows implemented at facilities such as Lawrence Livermore National Laboratory and Oak Ridge National Laboratory. Application areas include structural virology (complementary to work on SARS-CoV-2 by groups at NIH Vaccine Research Center), membrane protein pharmacology with links to projects at Pfizer and Merck, and fundamental studies of ribosomes and spliceosomes referencing discoveries from Max Planck Institutes and EMBL-EBI. Collaborative programs with translational centers emulate partnerships seen between Broad Institute and academic labs for target-based drug design.
Access operates through peer-reviewed proposal cycles and rapid-access mechanisms adapted from models used by Diamond Light Source and Advanced Photon Source; users include investigators from University of Washington, University of Texas Southwestern Medical Center, Fred Hutchinson Cancer Research Center, and industry partners. Training encompasses hands-on microscopy courses, on-site workshops inspired by EMBO training schools, and remote-support initiatives employing cloud resources akin to those at Google Cloud and Amazon Web Services for large-scale processing. User support provides assay development, specimen optimization, and data-analysis consultancy with staff trained to methodologies published by leaders at Columbia University Irving Medical Center and Yale School of Medicine.
Governance structures mirror consortia-based oversight seen at National Nanotechnology Coordinated Infrastructure and include advisory committees with representatives from NIH, academic stakeholders such as University of California, Berkeley, and industry advisors with ties to Thermo Fisher Scientific. Funding streams blend federal appropriations from agencies like National Institute of Allergy and Infectious Diseases, competitively awarded grants similar to those from National Science Foundation, fee-for-service revenue typical of user facilities, and strategic investments from philanthropic organizations comparable to Gordon and Betty Moore Foundation contributions.
The Facility has enabled high-impact structures deposited to the Protein Data Bank that advanced antiviral drug design and informed vaccine antigens, supporting publications in Nature, Science, and Cell. Notable achievements include determination of previously intractable membrane-protein complexes, cryo-ET visualizations of intracellular assemblies analogous to breakthroughs at Janelia Research Campus, and training of hundreds of researchers who later joined teams at Genentech, Biogen, and academic centers such as Princeton University and University of Chicago. The Facility’s datasets have contributed to method development in software projects like RELION and cryoSPARC and informed national strategies for biomedical imaging similar to reports by National Academies of Sciences, Engineering, and Medicine.
Category:Cryo-electron microscopy facilities