Advancements in understanding circadian rhythms: Latest research

Unveiling the mechanisms of circadian clock timing with cryptochrome-timeless structure.

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Circadian rhythms are biological processes that follow a roughly 24-hour cycle and are present in most living organisms. They regulate essential bodily functions like sleep-wake cycles, metabolism, and hormone production. Recent research has shed new light on how these rhythms work, providing insight into potential treatments for sleep disorders.

New research published in Nature sheds light on the mechanisms behind circadian rhythms. Using cryo-electron microscopy techniques, researchers identified the structure of the circadian rhythm photosensor and its target in fruit flies. The study focused on cryptochromes, critical components of circadian clocks in plants and animals, including humans. 

The researchers found that the TIM protein and the PER protein inhibit the genes responsible for their production, establishing an oscillation in protein levels. These findings could lead to new treatments for sleep disorders such as jet lag and insomnia.

This oscillation represents “the ticking of the clock and seems to be fairly unique to the circadian rhythm,” said senior author Brian Crane, the George W. and Grace L. Todd Professor and chair of chemistry and chemical biology in the College of Arts and Sciences.

Crane said blue light changes the chemistry and structure of cryptochrome’s flavin cofactor, allowing the protein to bind the TIM protein and inhibit TIM’s ability to repress gene expression and thereby reset the oscillation. 

New research has shed light on the mechanisms behind circadian rhythms and has the potential to lead to new therapies for sleep disorders. 

Using innovative cryo-electron microscopy techniques, a team of multidisciplinary researchers has identified the structure of the circadian rhythm photosensor and its target, TIM, in fruit flies. The researchers focused on fruit fly cryptochromes, critical components of the circadian clocks of plants and animals, including humans. They found that TIM, along with its partner, PER, acts together to inhibit the genes responsible for their production, establishing an oscillation in protein levels. 

The study also uncovered an unexpected link between DNA damage repair and circadian rhythm regulation. The researchers believe the study may help to understand sleep behavior regulation in humans.

New research has revealed the mechanism behind circadian rhythms by studying the Cry-Tim complex through cryogenic electron microscopy. The study found that the Cry flavin cofactor undergoes conformational changes that affect the molecular interface and a phosphorylated segment in Tim that regulates the clock period.

The N-terminus of Tim inserts into the restructured Cry pocket to replace the autoinhibitory C-terminal tail, which explains how the long-short Tim polymorphism adapts flies to different climates. The study also sheds light on the interactions between components that regulate sleep behavior in people.

In a study, a multidisciplinary team of researchers used innovative cryo-electron microscopy techniques to identify the structure of the circadian rhythm photosensor and its target in fruit flies. Cryptochromes, critical components of circadian clocks in plants and animals, including humans, were the focus of the study. In fruit flies and other insects, cryptochromes serve as primary light sensors that activate in response to blue light, setting circadian rhythms.

Known as “Timeless” (TIM), it is a large, complex protein that was previously difficult to image, making its interactions with cryptochrome poorly understood. By identifying the structure of the cryptochrome-TIM complex, the researchers gained new insights into the workings of circadian clocks.

The researchers found that the TIM protein, along with its partner, the Period (PER) protein, acts together to inhibit the genes responsible for their production. This feedback loop creates an oscillation in protein levels, which is the basis of the circadian rhythm. These findings provide new hope for developing treatments for sleep disorders such as jet lag and insomnia by targeting the molecular mechanisms that regulate circadian rhythms.

In summary, the recent study sheds new light on the mechanisms behind circadian rhythms, revealing the intricate feedback loops that regulate these biological processes. The findings provide a basis for future research into treatments for sleep disorders that target the molecular mechanisms involved in regulating circadian rhythms.

Moreover, the study has explained how the long-short Tim polymorphism in flies adapts them to different climates. These findings may deepen our understanding of circadian rhythm regulation and open up new possibilities for developing therapies targeting related processes. Furthermore, the interactions observed between the proteins in fruit flies can be mapped onto human proteins. This may help us understand critical interactions between components that regulate sleep behavior in people.

Journal Reference:

  1. Changfan Lin, Shi Feng, Cristina C. DeOliveira ,Brian R. Crane. Cryptochrome–Timeless structure reveals circadian clock timing mechanisms. Nature (2023). DOI: 10.1038/s41586-023-06009-4
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