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Enzymes are the fundamental stuff of life. These proteins regulate essential processes in all living things, including breathing, digestion and muscle functions.

That’s why Margaux Pinney, PhD, sees tremendous potential for their use in anti-cancer, antimicrobial and antiviral drugs. Because proteins can adapt to extremes, she also believes they can shine a light on how living organisms might adapt to the rising temperatures caused by climate change.

Pinney is a 2022 UCSF Sandler Fellow, a group of up-and-coming scientists given principal investigator status directly after earning their doctorate. Her lab studies how enzymes adapt to new and changing environments, with a focus on how they adapt to changing temperatures.

“There are organisms that live at really low temperatures and others that live at really high temperatures. These organisms have the same types of enzymes, but with key changes to enzyme structure and function that allow them to adapt to such different environments,” she says.

Because enzymes are highly interconnected, their functions multifaceted, and their cellular environments complex, identifying what affects their structure and function requires methods beyond traditional biochemistry, Pinney says. That’s why her lab uses high-throughput methods, or automated equipment, to quickly test thousands of biological samples.

“By doing experiments on a large scale, we can start to figure out how and why enzymes adapt,” she says. “We can make thousands of mutations and measure how those mutations affect the stability of an enzyme at different temperatures, along with the enzyme’s ability to function at those temperatures.”

These insights could be critical to understanding how organisms will adapt to a warmer world.

“As the world becomes hotter due to climate change, organisms, unfortunately, have to adapt or perish. Our research will tell us how easy or hard that is going to be for organisms at the molecular level,” Pinney says.

Since enzymes drive so many essential functions in living things, disruptions can lead to disease. Better understanding how and why enzymes adapt could help researchers tap into the potential for using them in targeted anti-cancer, antimicrobial and antiviral drugs.

“People have slightly different enzyme structures that can affect their reaction to drugs. By better understanding the relationship between enzyme structure and function, we can work to design better drugs to target these proteins,” Pinney says. “Understanding the enzymes involved in drug metabolism and resistance can also help explain why some people develop resistance to certain drugs, and potentially how to overcome it through new therapies.”

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