Goodbye jet lag: Using a protein to reset the body clock

Researchers are on track to develop a new method to counteract jet lag. The experts have unlocked the mystery of a specific protein that regulates our body clock – Casein Kinase 1 delta (CK1δ).

Circadian rhythms are the inherent 24-hour cycles affecting our sleep-wake patterns and overall daily functions. The research may ultimately allow us to adjust these biological rhythms.

Jet lag and the body clock protein

Led by experts at Duke-NUS Medical School and the University of California, Santa Cruz, the study could open new avenues of treatment related to the body’s circadian rhythm.

The research sheds light on the potential for alternative and more effective interventions for disorders tied to the biological clock.

The goal is to develop innovative treatments that help realign circadian rhythms, providing relief for those affected by sleep disruptions and improving overall health outcomes.

Proteins that run the body clock

CK1δ governs our circadian rhythm by tagging other proteins that play a part in our biological clock. This protein network essentially fine-tunes the timing of our circadian rhythms.

It is important to note that CK1δ itself can be tagged – which can alter its ability to control the proteins that run the body’s internal clock.

In previous work, scientists identified two distinct versions of CK1δ, known as isoforms δ1 and δ2. While these protein variants contain very few differences – a mere 16 building blocks or amino acids – these differences critically influence the function of CK1δ.

Controlling the protein and jet lag

Using advanced spectroscopy and spectrometry techniques, the researchers studied the tails of the proteins. The experts concluded that the unique tail sequences determine how the proteins are tagged.

Study co-author Carrie Partch is a professor in the Department of Chemistry & Biochemistry at the University of California, Santa Cruz.

“Our findings pinpoint to three specific sites on CK1δ’s tail where phosphate groups can attach, and these sites are crucial for controlling the protein’s activity,” said Professor Partch.

“When these spots get tagged with a phosphate group, CK1δ becomes less active, which means it doesn’t influence our circadian rhythms as effectively. Using high-resolution analysis, we were able to pinpoint the exact sites involved – and that’s really exciting.”

Protein variants may influence jet lag

Professor David Virshup, director of the Cancer and Stem Cell Biology Program at Duke-NUS, discovered that the δ1 tail interacts more with the main part of the protein, leading to greater self-inhibition compared to δ2.

“When these sites are mutated or removed, δ1 becomes more active, which leads to changes in circadian rhythms. In contrast, δ2 does not have the same regulatory effect from its tail region,” said Professor Virshup.

Applications beyond jet lag

CK1δ plays a significant role in other crucial processes, including cell division, cancer development, and certain neurodegenerative diseases.

With the newfound understanding of CK1δ’s activity, new strategies could be developed for not just circadian rhythm disorders but also for a range of conditions.

Professor Patrick Tan from Duke-NUS elaborated on the broader implications that this research could have on our health and well-being.

“Regulating our internal clock goes beyond curing jet lag – it’s about improving sleep quality, metabolism and overall health,” said Professor Tan.

Going forward, the researchers will explore how real-world factors such as diet and environmental changes can influence the tagging sites on CK1δ.

This could potentially shed light on how these elements affect our circadian rhythms and might be a stepping stone to practical solutions for managing disruptions caused by jet lag.

Resetting the body clock

The implications of this discovery extend well beyond basic sleep regulation. For frequent travelers, overcoming jet lag has long been a challenge.

By targeting the CK1δ protein, the researchers are optimistic about developing treatments that can reset the body’s internal clock faster and more effectively.

This could mean adjusting to new time zones with ease, reducing the usual symptoms of fatigue, and enhancing overall well-being.

As these findings advance, the potential for creating accessible, targeted therapies that specifically address jet lag grows, offering new hope to those who are constantly on the move.

The study is published in the journal Proceedings of the National Academy of Sciences.

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