Scientists discover a secret to regulating our body clock, offering new approach to end jet lag

科学家发现调节生物钟的秘密，为结束时差反应提供了新方法

Scientists from Duke-NUS Medical School and the University of California, Santa Cruz, have discovered the secret to regulating our internal clock. They identified that this regulator sits right at the tail end of Casein Kinase 1 delta (CK1δ), a protein which acts as a pace setter for our internal biological clock or the natural 24-hour cycles that control sleep-wake patterns and other daily functions, known as circadian rhythm.

Published in the journal PNAS, their findings could pave the way for new approaches to treating disorders related to our body clock.

CK1δ regulates circadian rhythms by tagging other proteins involved in our biological clock to fine-tune the timing of these rhythms. In addition to modifying other proteins, CK1δ itself can be tagged, thereby altering its own ability to regulate the proteins involved in running the body's internal clock.

Previous research identified two distinct versions of CK1δ, known as isoforms δ1 and δ2, which vary by just 16 building blocks or amino acids right at the end of the protein in a part called the C-terminal tail. Yet these small differences significantly impact CK1δ's function. While it was known that when these proteins are tagged, their ability to regulate the body clock decreases, no one knew exactly how this happened.

Using advanced spectroscopy and spectrometry techniques to zoom in on the tails, the researchers found that how the proteins are tagged is determined by their distinct tail sequences.

Howard Hughes Medical Institute Investigator Professor Carrie Partch explained: "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. 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."

Having first studied this protein more than 30 years ago while investigating its role in cell division, Professor David Virshup elaborated: "With the technology we have available now, we were finally able to get to the bottom of a question that has gone unanswered for more than 25 years. We found that the δ1 tail interacts more extensively with the main part of the protein, leading to greater self-inhibition compared to δ2. This means that δ1 is more tightly regulated by its tail than 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."

This discovery highlights how a small part of CK1δ can greatly influence its overall activity. This self-regulation is vital for keeping CK1δ activity balanced, which, in turn, helps regulate our circadian rhythms.

The study also addressed the wider implications of these findings. CK1δ plays a role in several important processes beyond circadian rhythms, including cell division, cancer development, and certain neurodegenerative diseases. By better understanding how CK1δ's activity is regulated, scientists could open new avenues for treating not just circadian rhythm disorders but also a range of conditions.

Professor Patrick Tan commented: "Regulating our internal clock goes beyond curing jet lag -- it's about improving sleep-quality, metabolism and overall health. This important discovery could potentially open new doors for treatments that could transform how we manage these essential aspects of our daily lives."

1. internal [ɪnˈtɜːnl] adj. 内部的；内在的

2. regulator [ˈreɡjuleɪtə(r)] n. 调节器；监管者

3. protein [ˈprəʊtiːn] n. 蛋白质

4. circadian [sɜːˈkeɪdiən] adj. 生理节奏的；昼夜节律的

5. alter [ˈɔːltə(r)] v. 改变；更改

6. distinct [dɪˈstɪŋkt] adj. 不同的；明显的

7. sequence [ˈsiːkwəns] n. 序列；顺序

8. pinpoint [ˈpɪnpɔɪnt] v. 准确确定；精确定位

9. elaborate [ɪˈlæbəreɪt] v. 详细说明；精心制作

10. metabolism [məˈtæbəlɪzəm] n. 新陈代谢