Argonne X-rays Advance Disease Monitoring

Aeriel-view-of-the-APS

Using the Advanced Photon Source, researchers are creating smart proteins to better monitor diseases like cancer and thyroid disorders.

A team led by Nobel Prize winner David Baker used artificial intelligence and the Advanced Photon Source to design proteins that sense key molecules in the body. This work could lead to easier and more accurate health monitoring, from cancer treatment to liver and thyroid testing.

Some of the most important molecules in our bodies—like those used in cancer treatments or that signal thyroid issues—are tiny and hard to track. Scientists need tools to detect these “small molecules” quickly and reliably. That’s where a breakthrough from the University of Washington comes in.

Working with the U.S. Department of Energy’s (DOE) Argonne National Laboratory, a team led by Nobel Prize-winning scientist David Baker created proteins that can detect these small molecules in new ways. This work was made possible by the powerful X-rays at the Advanced Photon Source (APS), a DOE Office of Science user facility at Argonne.

To develop these new protein sensors, the team used artificial intelligence. Their goal was to build proteins that could find and attach to small molecules—like methotrexate, a common cancer drug, or thyroxine, a hormone related to thyroid health. Once a protein finds one of these molecules, it sends out a signal, similar to how a COVID test changes color to show a positive result.

The APS was crucial in this process. After designing the proteins using computer models, the team used APS’s ultrabright X-rays to examine the actual shape of the proteins at the atomic level. This helped confirm that the designs worked in real life—not just in simulations.

“These X-rays help us see the exact structure of the proteins,” said Kay Perry, a scientist with the Northeastern Collaborative Access Team at the APS. “It’s one of the best ways to make sure any computer predictions are accurate.”

“Smart” sensors are proteins that light up or block electrical signals whenever they detect certain molecules. These signals can then be measured easily, like flipping a switch when the right molecule is present. Previously, scientists needed to iteratively test through may trials when developing such a “smart” sensor. Baker’s work provides a pathway to faster and more accurate “smart” sensor design.

These sensors could one day be used at home to monitor health conditions like liver disease, cancer, or thyroid problems. Today’s tests often can’t tell the difference between similar molecules, but these new protein-based sensors are much more specific.

Beyond medicine, the team is also looking at ways to use the technology to detect pollutants like microplastics or harmful chemicals in the environment.

This work was supported by the DOE Office of Science.

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