Summary We propose to establish the National Center for CryoEM Access and Training (NCCAT) to be housed at the Simons Electron Microscopy Center (SEMC), which is a part of the New York Structural Biology Center (NYSBC), based in New York, NY. NCCAT will provide access to state-of-the-art equipment, including specimen preparation robots, high-end microscopes and direct detectors, screening microscopes, and all the other ancillary equipment required to solve structures to the highest possible resolution using cryo electron microscopy (cryoEM) methods. A highly qualified technical team will provide direct support, guidance and assistance to ensure that structures of the highest quality are produced in the shortest possible time. An already well established cross-training program will be expanded and extended to provide training across a wide variety of skill levels and career goals. NCCAT will adopt an open and transparent application process to ensure equal-opportunity nationwide access. The operations at NCCAT will build on already established practices at SEMC/NYSBC and benefit from the overall vibrant environment as well as the expertise of many of the highly trained staff already in place. NCCAT will be housed in new, custom-built space that will provide optimal, environmentally stable conditions. The major instrumentation will consist of 3 Titan Krios TEMs equipped with direct detectors, energy filters and phase plates, and 3 screening microscopes equipped with CMOS cameras. Streamlined workflows, already well established, will expanded to ensure that we collect the highest quality data as efficiently as possible. A user service operation will provide on-site, remote-access, and mail-in data collection services with fair and equal access to a nationwide user base. We will guide and assist users with all aspects of cryoEM, including sample preparation, data collection and image processing. A training program will encompass 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 fully embedded researchers who will be expected to graduate to running their own cryoEM research laboratories. While we anticipate that we will initially be called to serve and train mostly in the area of single particle cryoEM, we are well positioned to provide support in the area of cryoET that we predict will grow rapidly. While the goals of NCCAT are not innately innovative it is our intention to set the standard as one of the first world class, nationally accessible cryoEM access and training facilities that is freely and fairly available to all researchers in the US, and to continually strive to enable science of the highest quality and value.

Project Narrative CryoEM has unique capabilities for the study of biological systems that are not accessible to other structural methods. Recent technical advances in single-particle cryoEM have made it capable of generating reliable atomic models of complete and fully functional macromolecular complexes. NCCAT will provide nationwide access to state-of-the-art equipment, technical support, and cross-training to enable the production and analysis of high-resolution cryoEM structures.