NCCAT: National Center for CryoEM Access and Training

Project Summary/Abstract The National Center for CryoEM Access and Training (NCCAT) enables users to solve macromolecular structures rapidly and to the highest possible resolution using cryo-electron microscopy (cryoEM) methods. We propose to continue to: (1) Provide access to state-of-the-art equipment, (2) Maintain a highly qualified technical team offering direct support, guidance, and assistance, (3) Operate a comprehensive cross-training program for users across diverse skill levels and career goals, and (4) Ensure equal opportunity nationwide access through an open and transparent application process. NCCAT is housed at the Simons Electron Microscopy Center (SEMC) within the New York Structural Biology Center (NYSBC) in New York City. NCCAT’s established operations at SEMC and NYSBC benefit from the vibrant environment and expertise of existing highly trained staff. NCCAT occupies custom-built space that provides optimal, environmentally stable conditions. The primary instrumentation consists of 4 dedicated Titan Krios TEMs, each equipped with direct detectors and energy filters; 1 (soon to be 3) dedicated Glacios TEMs, each equipped with direct detectors, and 3 side entry screening microscopes (1 of which is dedicated to NCCAT) equipped with CMOS cameras. These are augmented by all ancillary equipment needed for the cryoEM workflow, including several classes of vitrification and sample preparation equipment. NCCAT provides on-site, remote-access, and mail-in data collection services with fair and equal access to a nationwide user base, and we guide and assist users with all aspects of cryoEM, including sample preparation, data collection, data processing, data analysis, and structure refinement. By providing users with access to streamlined workflows and resources, NCCAT allows researchers to collect high-quality data quickly and efficiently, which will lead to faster progress in structural biology research. NCCAT’s training program encompasses a full range of expectations, from the basics required to ensure that users produce valid structures, through more detailed training for users seeking independence, to those expected to run cryoEM research laboratories. A well-established grid preparation and screening service program supports new practitioners of cryoEM methods and/or laboratories that lack local facilities and resources to optimize sample and grid preparation conditions and, when possible, obtain preliminary cryoEM processed data. We propose to be transformative by setting the standard for access and training to cryoEM technology. By facilitating the shift from the current model of isolated and expensive facilities to a unified and more efficient Center, we will enable science of the highest quality and value and therefore provide essential foundational knowledge needed to develop new therapies, diagnostics, and clinical practices to better human health.