National network for cryo-ET nears completion

In 2020, the National Institutes of Health announced the formation of a National Network for Cryo-ET: four funded centers, with UW-Madison as a hub that also coordinates activities. The network will provide access to and training in routine and advanced cryo-electron tomography specimen preparation, new methods development, high-resolution data collection and computational analysis.

Over the past year, scientists, technologists, engineers and construction crews have been working to get the new national hub up and running. Laboratory construction is expected to be finished by October, says lead investigator Elizabeth Wright, a UW-Madison professor of biochemistry and affiliate with the Morgridge Institute for Research. Office and computation spaces should be ready by the end of 2021, while installations are expected to be complete by early 2022.

Cryo-electron tomography (cryo-ET) and cryo-electron microscopy (cryo-EM) are emerging technologies that can help scientists visualize life and its interactions on sub-nanometer scales, giving them a look at biological structures and phenomena with unprecedented detail. Cryo-ET complements cryo-EM by creating three-dimensional (3D) images. Unlike single particle analysis cryo-EM, which averages thousands of objects to arrive at a 3D structure, cryo-ET creates a 3D structure from unique targets.

While UW-Madison recently installed four highly advanced electron microscopes as part of the Department of Biochemistry’s Cryo-EM Research Center, the NIH initiative paves the way for at least two more electron microscopes to accommodate national demand. The hub will house a next-generation transmission electron microscope (TEM), a wet lab for sample preparation, a focused ion beam scanning electron microscope (FIB-SEM), a leading-edge cryo-confocal fluorescence optical microscope, world-leading plunge freezing instruments, and more as well as training spaces suitable for in-person, virtual, and remote training activities. Training areas will also contain an auditorium for lectures and a seminar room for directed trainings and remote operation of several advanced microscopes.

Photo of Elizabeth R. Wright
Professor Elizabeth Wright.

“The national center will be a hive for nucleating science around the use of cryo-ET for biological studies in situ,” said Wright. “The physical space and resources will give campus visitors a ‘home base’ to perform computation and connect with other investigators.”

As construction crews get the lab and office spaces ready, research staff Keith Thompson and Matt Larson and hub scientists are coordinating activities between the NIH, network centers and center users. This, in part, involves gathering research proposals from scientists who want to receive training through the network and coordinating with other centers to help successful applicants receive on-site training and instrument time.

In their first call for training proposals, the UW-Madison hub received 32 applications from mature and early-career investigators around the country. Applications are peer-reviewed by a team of cryo-EM researchers from outside the network.

“The goal of this application-based training [through the national network] is to build and expand the cryo-ET community and to help scientists become independent cryo-ET practitioners. Investigators will return to their home institutions after training at the National Cryo-ET Network Centers, prepare samples, and teach other scientists these methods. Then, they will return to one of the national, regional or local cryo-ET or cryo-EM centers to collect data,” said Wright.

The network also wrapped up its first webinar series this summer. Speakers from each of the four National Network centers discussed the fundamentals of cryo-ET and how to answer different biological questions using the technology. UW-Madison hub staff member Keith Thompson organized the series, which had approximately 1,000 registrants worldwide.

Wright, who also oversaw the development of the UW-Madison Cryo-EM Research Center, says that outreach efforts such as the webinar series, virtual office hours, newsletters and one-on-one discussions are essential activities for engaging with groups of potential cryo-EM investigators.

“Cryo-ET is still a developing technology with a relatively small workforce. There is currently limited access to the necessary equipment and expertise,” said Wright. “One of our major goals as a center and a network of centers is to bring more trained researchers into this field.”

Accordingly, outreach and education are integral to the mission of the National Centers, the growth of the cryo-ET community, and the development of cryo-ET technologies that facilitate research. Outreach initiatives, on-site training and cross-training will continue to expand as the network develops.

Written by Catherine Steffel, Ph.D. More information about the National Network for Cryo-ET can be found here. Funding for the National Network for Cryo-ET is provided by the National Institutes of Health. Sister centers of the UW-Madison based Midwest Center for Cryo-Electron Tomography are the CU Boulder Center for Cryo-ET, the National Center for In-situ Tomographic Ultramicroscopy, and the Stanford-SLAC CryoET Specimen Preparation Service Center.