Cryo-ET Center to Expand as Demand for the Technology Grows

Photo of Elizabeth R. Wright
Professor Elizabeth Wright.

The University of Wisconsin–Madison is home to the Midwest Center for Cryo-Electron Tomography (MCCET). Since this NIH-funded center opened in 2021, UW has become a national epicenter of cryo-electron tomography (cryo-ET) and innovative biomedical and life sciences research using cryo-ET techniques.

MCCET will now be expanding, thanks to $15 million in supplemental funding from the National Institutes of Health (NIH) Transformative High-Resolution Cryo-Electron Microscopy Program. The program supports broadening access to cryo-ET for biomedical researchers.

“The goal with this funding is to provide center users with access to instruments that are at the technological cutting edge and to extend the range of workflows available,” says Elizabeth Wright, professor in the Department of Biochemistry and director of MCCET. “The new instrumentation will allow us to increase throughput in the center by providing solutions for faster sample milling with less sample damage, and improved imaging for large cell, organism, and tissue samples.”

MCCET is the central Hub for the National Network of Cryo-ET Centers, which consists of four cryo-ET research centers across the United States. The Network currently supports 148 research projects from about 350 principal investigators and their trainees, and receives requests from 15-30 new projects each quarter. “This expansion is essential for MCCET and for the entire network,” says Wright. “With the existing microscopes running at full capacity, it would take approximately 2.8 years to collect the necessary cryo-ET data for all current projects.”

The supplemental funding from the NIH will support recruiting new staff at MCCET, as well as installing advanced microscopes, other equipment, and software updates. These additions — which will allow the center to process samples with greater efficiency and improve image quality and quantities — have the potential to reduce wait time for researchers and will help expand currently available workflows with newer research strategies. Construction on the new spaces is expected to begin in early 2024.

Eight workshop participants, gathered in the MCCET conference room, learn how to collect data on a microscope in a different room.
Participants in a spring 2023 MCCET cryo-electron tomography workshop learn how to collect tomography data of bacteria on the Krios G4 cryo-TEM. Photo by Paul Escalante/Biochemistry.

Cryo-electron microscopy (cryo-EM) allows researchers freeze biological molecules and cells at ultracold temperatures, stopping biological processes in action and capturing images of cellular structures frozen in time at scales smaller than the size of a single molecule of water. Through cryo-electron tomography (cryo-ET), researchers can examine the three-dimensional structures of organisms, cells and organelles, and viruses in their native states by creating a composite of 2D images of a frozen sample taken from many different angles.

MCCET workshop participants listen to a Thermo Fisher Scientific representative as they work in the MCCET space.
Participants in a spring 2023 MCCET cryo-FIB milling workshop learn how to FIB-mill HeLa cells to produce lamella with the Aquilos 2 system. Photo by Jacqui van Twest/MCCET.

MCCET’s staff and equipment provide researchers at UW and across the world with support for sample preparation, imaging, and computation, as well as training on these processes. Using these technologies, researchers have studied the structure, function, and processes of biomolecules and biomolecular phenomena on the smallest scales, from protein structure, bacterial motility, and mechanisms essential to DNA replication, to virus structure and brain cell morphology.

A core aspect of MCCET’s work and that of the National Network of Cryo-ET Centers, which is fully funded through the NIH, is to open the door to discovery by making cryo-ET accessible to all researchers who may not otherwise have access to resources available to scientists at UW–Madison or their home institutions.

“We are extremely grateful to the NIH for their continued support of MCCET, the National Network of Cryo-ET Centers, and members of the cryo-EM, structural biology, and cell biology communities,” says Wright. “This additional funding will ensure that we are able to improve the capabilities of our facility, which will mean that MCCET and its staff can reach and help more investigators in need of cryo-ET resources, access, and training.”

Written by Renata Solan.

Instruments purchased through supplemental funding from the NIH Transformative High-Resolution Cryo-Electron Microscopy Program will include a 300 kV Cryo-Transmission Electron Microscopy (funded by National Institute of General Medical Sciences) and a Plasma Focused Ion Beam-Scanning Electron Microscope (funded by the NIH Common Fund).