All together now: $5.5M CPRIT grant
If you build it, they will come. Once they arrive, you’ll want to use their time wisely.
That is the challenge and the promise of UT Southwestern Medical Center’s $22.5 million cryo-electron microscopy facility now running 24 hours a day, seven days a week.
The facility opened in 2016 with a unique array of instruments that put it at the vanguard of the “resolution revolution” in cryo-EM technology. It includes a Titan Krios, a microscope that stands more than 12 feet tall and shoots a thin stream of highly focused electrons at flash-frozen protein samples held by the machine’s robotic arm. Cryo-EM enables atomic-level views of proteins that resist the crystallization necessary for traditional X-ray crystallography.
The first biological structures solved in the new facility were recently published in the prestigious journal Nature.
Expansion plans are underway to meet the demand of researchers campuswide interested in using the new technology. After bringing together some of the world’s top cryo-EM experts at UT Southwestern, the goal now is to become a world leader in building the community needed to make the best possible use of that microscopy power. In a world of scientific inquiry, the question becomes how to make the expensive technology available to the largest number of campus researchers to produce the most important science.
“The cryo-EM field is booming, and the world is catching up. We are trying to stay ahead of the curve.”
To speed the creation of a culture that fosters collaborations of the highest caliber, UT Southwestern is taking a multipronged approach. First, it is working to train researchers from more than a dozen departments to use the new technology. Second, it will use a recent $5.5 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to create a cryo-EM service that will become a “one-stop shop” for cryo-EM structures.
The cryo-EM service will enable faculty to get single-particle cryo-EM studies done by core laboratory staff, says Dr. Daniela Nicastro, Associate Professor of Cell Biology and Biophysics and Director of the cryo-EM facility. “We will have a cryo-EM service person, and projects will emphasize cancer research,” she says.
The new cryo-EM service will be embedded in the University’s existing Structural Biology Laboratory (SBL), which has a long history as an X-ray crystallography core, run by Dr. Diana Tomchick, Professor of Biophysics and Biochemistry. In addition to support service staff, the CPRIT grant will be used to buy another instrument and purchase robotics for sample preparation in order to increase the throughput for cryo-EM projects on campus.
By placing the new service within the SBL, staff trained in both technologies – cryo-EM and X-ray crystallography – can advise researchers on the best one for individual projects, Dr. Tomchick says.
“The SBL has an excellent track record on X-ray crystallography and has the infrastructure to provide service to laboratories that have structural biology questions,” says Dr. Nicastro, adding that there will be a small charge for the service.
Meanwhile, work continues to expand access to the main cryo-EM facility. The demand for time on the machines is understandable because cryo-EM can be used to determine the structure of proteins and protein complexes that have long resisted crystallization and thus evaded X-ray crystallography. That category includes proteins that reside in cell membranes and encompass some of the most intriguing proteins in human health and disease.
The situation is similar to global explorers centuries ago who endeavored to be the first to travel to new continents. By solving important biological structures for the first time, cryo-EM holds the promise of understanding the inner workings of disease-related proteins and of revealing the locations at which bioactive molecules and potential pharmaceuticals might bind.
As a result, the cryo-EM facility staff is working as fast as it can to train as many researchers from as many departments as possible, Dr. Nicastro explains.
“Right now, 35 users from 24 different labs in 12 different departments have been or are being trained to prepare samples and to use the two cryo-EM microscopes that UT Southwestern currently owns,” she says.
“The cryo-EM field is booming, and the world is catching up. We are trying to stay ahead of the curve and we would like to get another big instrument,” she says. “That would keep UT Southwestern in the company of a handful of institutions worldwide with advanced capability in this burgeoning field.”
“For now,” she adds, “establishing the cryo-EM single-particle service provides a resource to UT Southwestern researchers that is available at only a few places in the world.”