Super ‘cool’ electron microscope to accelerate discovery at KU Medical Center and throughout the region
The new cryogenic electron microscope can reveal the structure of flash-frozen proteins and other biomolecules at nearly atomic resolution, enabling researchers to understand diseases and design drugs to fight them.
A new cryogenic electron microscope that arrived April 13 at the University of Kansas Medical Center is set to revolutionize research at the medical center and throughout the region.
KU Medical Center is now the only institution in the area to offer cryogenic electron microscopy.
The $4 million acquisition, a Glacios cryo-EM manufactured by Thermo Fisher Scientific, was made by the Office of the Executive Vice Chancellor at KU Medical Center, The University of Kansas Cancer Center and the University of Kansas School of Medicine.
Cryogenic electron microscopy, known as cryo-EM, produces three-dimensional images, at nearly atomic resolution, of proteins, viruses and other biomolecules. These detailed images are critical to understanding what causes different diseases and designing drugs to treat them.
“This technology will increase the throughput of the science and allow us to do things we couldn't do before, asking and answering questions that we hadn't been able to ask and answer before,” said Peter Smith, Ph.D., senior associate vice chancellor for research at KU School of Medicine.
Sometimes referred to as the “resolution revolution,” this technology has enabled scientists to map the structure of the Zika virus, which can cause birth defects. It also has been used to determine the shape and make-up of plaques in the brain that are associated with Alzheimer’s disease and to decipher the unique structure that makes E. coli and other bacteria able to move.
X-ray crystallography, which requires compressing the proteins or other samples into crystals, also produces intricate three-dimensional images, but some biomolecules do not crystallize because they are floppy or unstable. With cryo-EM, the protein is flash-frozen before being inserted into the microscope, where it is bombarded with electrons to generate thousands of images of the molecules in various orientations. Computer software processes these images to construct a three-dimensional model of the protein.
Three years after the scientists who developed this technology won the 2017 Nobel Prize in Chemistry, cryo-EM was instrumental in determining the structure of the SARS CoV-2 spike protein and thus the development of the vaccines for COVID-19. Jason McLellan, Ph.D., a structural biologist from the University of Texas who led the team that determined the structure of that spike protein, will be the keynote speaker at an open house for KU Medical Center’s new instrument, scheduled for May 9.
In the past, researchers at KU Medical Center wanting to use cryo-EM imaging had to send their samples to other institutions across the country, which can take months, Smith said. Now they will be able to produce images in a matter of days or even hours. The new cryo-EM is housed in the electron microscopy research laboratory in the Lied building, which is near Hixson Atrium on the medical center’s Kansas City campus.
“This will be a regional resource,” said Michelle Winter, assistant dean of laboratory operations at KU Medical Center. “There is nothing else like it in the state of Kansas, and even in Missouri, it’s still very limited. We have a number of people across several institutions, including KU Medical Center, the Stowers Institute and Children's Mercy, who are ready to use this.”
One of the first will be Bret Freudenthal, Ph.D., associate professor of biochemistry and molecular biology at KU Medical Center and a member of The University of Kansas Cancer Center. His lab uses cryo-EM to reveal how DNA damage is identified, removed and repaired by cellular proteins. Understanding this process at the structural level is essential to understanding the connection between DNA damage and repair and diseases such as cancer. In the past, Freudenthal’s lab sent their samples to other institutions with cryo-EM facilities and waited weeks to months for the analyses.
“With the new cryo-EM, we can quickly make new discoveries that we hope will lay the foundation for new therapies,” said Freudenthal. “In this way, the cryo-EM at KU Medical Center will supercharge our research program and accelerate our studies, all while training the next generation of scientists.”