Since its much-anticipated opening three years ago, the Cryo Electron Microscopy Core Facility at UMass Medical School has trained hundreds of scientists from the region’s research universities; analyzed thousands of samples from academic and commercial labs around the country; and become a resource for faculty, postdocs and students on campus. Now the facility is expanding with new equipment, new users and a broader vision for how it can advance biomedical research underway at UMMS and beyond.
“We assist users at all levels to collaborate and share knowledge. Everyone wants to use cryo-EM but not many know how,” said Chen Xu, PhD, associate professor of biochemistry & molecular pharmacology and the director of the cryo-EM facility. “We now serve almost 100 academic institutions and labs, and we are unique in providing full service to industry.”
Cryo-EM is a breakthrough technology for visualizing the detailed structure of cells, viruses and proteins at near-atomic resolution with broad applications in structural biology and drug design. The technology allows scientists to answer questions about cellular processes that are essential to life, as demonstrated by studies by UMass Medical School structural biologist Andrei Korostelev, PhD. The Korostelev lab uses cryo-EM and other experimental techniques to understand molecular mechanisms of translation regulation on ribosomes in protein synthesis.
“This is a very exciting time. As a post-doc using X-ray crystallography, I was always dissatisfied with seeing just a snapshot and trying to tease out mechanisms. I didn’t even dream about being able to see molecules moving,” said Dr. Korostelev, associate professor of RNA therapeutics. “With cryo-EM, there is an opportunity to capture images of the ribosome in different conformations and then, by combining the structures into a pathway in a projector, we can see how it works in motion.”
One of the proponents for bringing the Massachusetts Cryo-Electron Microscopy Facility to UMMS, Korostelev received the Earl and Thressa Stadtman Scholar Award from the American Society for Biochemistry & Molecular Biology in 2018. In 2017, the RNA Society named him the recipient of its Young Investigator Award for employing cryo-EM technology to visualize the detailed movements, molecular rearrangements and dynamic atomic interactions of ribosome function that make protein synthesis so accurate.
Anna Loveland, PhD, studies ribosome structure during mRNA translation and peptide elongation as a postdoc in the Korostelev lab. “These incredible tools have changed so much since I started doing cryo-EM in 2012,” she said. “They allow us to see how these molecules move, how they do their processes, and visualize new parts and mechanisms that were hitherto inaccessible.” Dr. Loveland was recently recognized by the RNA Society for her work in the Korostelev lab with a member profile in its newsletter.
The UMMS Cryo-EM Core Facility operates around the clock for maximum productivity with three cryo-EM systems. The Titan Krios was acquired in collaboration with Harvard Medical School, supported by a grant of $5 million from the Massachusetts Life Sciences Center. The $4 million Talos-Arctica system was acquired with funding from the Howard Hughes Medical Institute. Also funded by HHMI, the most recent addition is the $1 million Aquilo CryoFocused Ion Beam/Scanning Electron Microscope system. With its added capabilities, the suite accommodates a wide spectrum of experimental techniques across multiple life sciences disciplines.
“We wanted to expand the capability and focus more on education,” said Xu. “Our reputation is so good that people are lining up to get access to our machines. We have an obligation to help them.”
More than 200 people are expected at the 4th New England Cryo-EM Symposium being hosted by UMass Medical School on Wednesday, Oct. 30. The event will focus on practical aspects of using the technology with presentations by cryo-EM users from UMMS and other research institutions including Harvard Medical School, MIT and Yale University.
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