‘It’s like being able to see a dime on the surface of the moon.’

When physicians observe or hear of symptoms in their patients, they order CT scans, MRIs or other types of imaging analyses to understand the causes.

Clinical imaging, however, does not illuminate the vast machinations of life that occur deeper within, at the Lilliputian level of individual proteins and other molecules. Chain reactions in this tiny domain determine whether good health continues, or diseases begin. To explore how the reactions foster disorder, scientists acquire images with state-of-the-art instruments capable of ultra-high resolution. They employ statistical models to work out molecular structures. The overall analysis yields sites of disease susceptibility that can be targets for drug therapies.

UT Health San Antonio is investing $5 million over the next three years in such a technology, called cryo-electron microscopy, or cryo-EM for short.

“We are essentially molecular photographers,” said Shaun Olsen, PhD, associate professor of biochemistry and structural biology and director of structural biology cores. “Some people take pictures of buildings. We take pictures of proteins and want to see what they look like in three dimensions.”

Cryo-EM visualizes proteins that are extremely difficult to image using other techniques, said Elizabeth Wasmuth, PhD, assistant professor of biochemistry and structural biology.

Cryo-EM is complementary to existing structural biology technologies at UT Health San Antonio. X-ray crystallography, for example, exposes a protein crystal to X-rays, diffracting the X-ray beam in directions according to the protein’s structure. Nuclear magnetic resonance (NMR) spectroscopy, meanwhile, demonstrates behavior of an atom nucleus when it is placed in a powerful magnetic field. Experts can infer structure from the behavior they observe.

“We look at molecules in levels of detail that are unparalleled,” Wasmuth said. “So, basically, it’s like being able to see a dime on the surface of the moon. This is the level of resolution that the techniques and tools of structural biology allow us to see about molecules inside cells, inside our bodies. Cryo-EM adds a powerful new dimension to our other methods.”

Some protein targets are too small to be visualized by existing techniques or have flexible, wiggly regions that impede the crystal formation, Wasmuth said. Cryo-EM flash-freezes proteins on thin layers of ice within milliseconds and barrages them with electron beams, generating biologically useful information.

“Having a cryo-EM system will allow us to observe drug targets that couldn’t be visualized by the other methods,” Wasmuth said. “The second week the cryo-EM facility became functional, we were able to solve the structure of a complex of proteins involved in DNA damage repair at impressively high resolution. I am confident that this tool is going to transform structural biology research here like we haven’t seen before.”

Much like the space telescopes in Chile, Hawaii and West Texas are indispensable shared resources for astronomers, cryo-EMs are invaluable shared resources for structural biologists.

“We have to remain competitive, and this is a question that a lot of academic medical centers are trying to decide right now: Where will we fit within the research environment?” said Jennifer Sharpe Potter, PhD, vice president for research. “This acquisition reflects our commitment to making San Antonio a biomedical hub for the United States and the world. The types of visualizations and the questions that this technology advances are investments in the long-term improvement of human health.”

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