Using cryo-EM technology to flash-freeze proteins can generate clues to curing disease

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

Clinical imaging, however, does not illuminate the processes of life that occur deeper within, at the 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.

Investments in human health

A technology called cryo-electron microscopy, or cryo-EM for short, is the hottest realm in structural biology today. The types of visualizations and the questions that this technology advances are investments in the long-term improvement of human health.

Cryo-EM is complementary to existing structural biology technologies. 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.

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

Big (very big) data

One dataset from two days on the cryo-EM system will be about 5 terabytes. A terabyte is 1 trillion bytes of information. Users require a graphic processing unit (GPU) and very powerful GPU workstations to render graphics at high speed and process the data. Some workstations cost on the order of $60,000 to $70,000 each.

Sifting the data requires graphics cards, and scientists using the cryo-EM technology compete for cards with people who mine Bitcoin and Ethereum cryptocurrencies. The price of the cards went through the roof when, after market fluctuations, there was increased mining activity and people were buying loads of graphics cards.

Cryo-EM as a scientific tool has boomed in the last decade due to advances in technology. Better microscopes, better optics and better computer programming have allowed new discoveries. Investigators can study the chain reactions that lead to most conditions, from tumors, dementia and cardiovascular disease to infectious diseases and brain injuries. Finally, cryo-EM capability may aid the acquisition of other instruments that will raise up science in San Antonio.

This information is from UT Health San Antonio, which is investing $5 million over three years in cryo-EM technology. The instrument, recently installed, is already being used by UT Health faculty to shed light on proteins involved in disease. Source of this article: Will Sansom, UT Health San Antonio, 210-567-2579,


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