Researchers discover flexible protein that sheds light on circadian rhythms

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Circadian clocks control the daily rhythms in living things, including humans, plants, fungi, and insects.

Disruptions to these clocks can lead to higher disease rates, such as certain cancers and autoimmune diseases.

Jennifer Hurley, Ph.D., from Rensselaer Polytechnic Institute, is focused on understanding how these circadian clocks work.

“Proteins are the building blocks of life, so understanding how they interact is crucial,” said Hurley. “This knowledge helps us understand organism behavior and offers opportunities to alter it.”

In a study published in Nature Communications, Hurley and her team discovered that a disordered clock protein called FRQ in the fungus Neurospora crassa interacts with another protein, FRH, in an unexpected way.

They found positively charged regions on FRQ that allowed it to bond with FRH across many different areas.

“Proteins are often thought to have a fixed shape, but some are flexible, like wet spaghetti noodles,” Hurley explained. “This flexibility can be important for protein interactions. For FRQ, its ‘noodliness’ lets it bond to FRH like a bear hug.”

The team found that this bear hug causes the circadian clock to switch from an hourglass, needing daily light resets, to a persistent oscillator, which maintains a continuous rhythm without light.

This persistent oscillator helps keep time, regulating behaviors and processes, even in conditions without light, like in the Arctic during winter.

Each new insight into circadian clocks brings us closer to being able to alter them for practical benefits. Manipulating circadian clocks could improve biofuel production, help combat jet lag, and ensure the health of shift workers.

In healthcare, understanding circadian rhythms offers many opportunities. “Our field calls this ‘chronotherapy,'” said Hurley. “If you get injured at a certain time of day, you heal faster than at another. We can schedule surgeries and time chemotherapy treatments to maximize effectiveness and minimize side effects.”

“This research by Professor Hurley and her team has advanced our understanding of circadian rhythms on a molecular level,” said Curt Breneman, Ph.D., dean of Rensselaer’s School of Science. “This in-depth knowledge opens the door to better managing circadian effects in humans.”

Hurley’s team included Meaghan S. Jankowski, Divya G. Shastry, Jacqueline F. Pelham, Joshua Thomas, and Pankaj Karande from Rensselaer, and Daniel Griffith, Garrett M. Ginell, and Alex S. Holehouse from Washington University School of Medicine.

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