Why is the circadian clock important? 2017 Nobel Prize in Physiology or Medicine

TL;DR

The circadian clock helps the body anticipate daily environmental changes instead of merely reacting to them. Its core mechanism is a self-sustained inhibitory feedback loop in which a substance accumulates, suppresses its own production, and then allows the cycle to restart, creating an oscillator that coordinates activity, sleep, and other processes across the body.

Transcript

professor Oliver them share the Nobel Committee could you describe to us what is circadian rhythm so circadian it writes Trumble actin so circuits around and day is babe and this is the daily rhythm we have to anticipate and adapt to the dramatically different conditions during day and night that arise from the rotation of the earth the three laure... Read More

Key Insights

• Circadian rhythm is a daily biological pattern that allows organisms to anticipate and adapt to the dramatically different conditions created by day, night, and the rotation of the Earth.
• The circadian clock is endogenous, meaning its rhythm originates within the organism rather than being only a direct response to external signals, although environmental mechanisms can adjust or entrain it.
• The laureates identified the clock mechanism by studying fruit-fly strains whose single-gene mutations produced long, short, or completely absent rhythms, then isolating the responsible gene and examining its function.
• The molecular clock is a self-sustained inhibitory feedback oscillator in which a substance builds up, suppresses its own synthesis, and later permits production to begin again, generating a repeating cycle.
• The evolutionary value of circadian timing is preparation, because organisms gain an advantage when they become ready to hunt, flee, hide, rest, or perform nighttime processes before environmental conditions change.
• Most cells have biological clocks, while a central clock in the brain controls overall rhythm and mechanisms elsewhere in the body help synchronize cellular clocks and coordinate their outputs.
• Sleep phase disorders can result from mutations in core clock genes that produce a shorter or longer phase, making them a solid example of a direct connection between clock machinery and human health problems.
• Human disease claims remain largely correlational beyond specific sleep phase disorders, while animal models provide stronger experimental evidence because researchers can disrupt the clock and directly observe resulting effects.

Questions & Answers

Q: What is a circadian rhythm and why is it important?

A circadian rhythm is the daily biological pattern that helps an organism anticipate and adapt to the dramatically different conditions of day and night. Anticipation is crucial because an organism may need to become active, hunt, escape, hide, or perform nighttime processes at the appropriate moment. This preparation offers an advantage over merely responding after environmental conditions have already changed.

Q: How does the molecular circadian clock work?

The molecular circadian clock works as an autonomous, self-sustained inhibitory feedback oscillator. A substance is produced and gradually builds up. Once present at the required level, it turns off its own synthesis. As the substance subsequently changes, production can begin again, creating a repeating oscillation. This regulated negative feedback provides the central concept behind the biological clock mechanism.

Q: How did the laureates discover the circadian clock mechanism?

The laureates used fruit flies as their model system and built on earlier experiments that had produced mutant strains with long, short, or absent rhythms. These mutations mapped to the same genetic location. The researchers isolated the associated gene, determined its identity, and then performed sequential experiments on that gene and several others to understand how the complete timing system functions.

Q: Is the circadian clock controlled by external signals?

The circadian clock is fundamentally endogenous, meaning its rhythm is generated inside the organism rather than being only a response to external signals. Before the laureates began their work, researchers already understood that the rhythm was endogenous and that individual genes could affect it. Later research also identified entrainment mechanisms that adjust the internal clock to environmental conditions.

Q: Does every cell in the body have a circadian clock?

Most cells in the body have a circadian clock. A central clock in the brain was known before the laureates made their discoveries, and it helps control overall rhythm. Researchers later found clocks in other parts of the body as well. Synchronization mechanisms coordinate these clocks, while output mechanisms allow other genes and biological processes to follow the same timing system.

Q: What health problems are directly linked to clock genes?

Sleep phase disorders provide a solid example of health problems directly connected to the clock mechanism. Mutations in some core clock genes can produce a shorter or longer phase, which then creates difficulties with sleep timing. Beyond these disorders, many proposed relationships between circadian disruption and specific human diseases remain correlations rather than firmly demonstrated causal conclusions.

Q: Why does jet lag make people feel unwell?

Jet lag illustrates what happens when the internal biological clock becomes misaligned with the surrounding environment. The body continues operating according to an internal schedule that no longer matches external time, making a person feel bad. Although jet lag is not described as a disease, it demonstrates why synchronization between internal rhythms and environmental conditions matters for normal functioning and well-being.

Q: What questions remain in circadian rhythm research?

Researchers still need to clarify how circadian timing affects human health and disease. The core machinery is more complex than its basic feedback concept suggests, involving additional stabilizing factors, interconnected loops, entrainment, synchronization across the body, and output mechanisms controlling other genes. The laureates' discoveries supplied tools and a mechanistic foundation for investigating these unresolved questions.

Summary

In this video, Professor Oliver describes the circadian rhythm and the groundbreaking discoveries made by the three Nobel laureates in the field. They solved the problem of understanding circadian rhythms and identified the mechanism that controls the clock. The circadian rhythm is important for anticipating and adapting to the daily changes in conditions during day and night, providing an advantage in evolutionary terms. The laureates used the fruit fly as a model system to study the function of genes involved in the circadian rhythm. The circadian clock is found in most cells of our body and is regulated by an auto regulatory self-sustained inhibitory feedback mechanism.

Questions & Answers

Q: What is the circadian rhythm?

The circadian rhythm is the 24-hour cycle that regulates biological processes in living organisms. It allows organisms to anticipate and adapt to the different conditions that arise from the rotation of the Earth.

Q: What problem did the Nobel laureates solve?

The existence of diurnal or circadian rhythms was known, but the mechanism behind them was not understood. There was a debate whether it was a response to external signals or something endogenous. The laureates discovered the mechanism that controls the machinery of the circadian clock.

Q: What were the key findings of the laureates?

The laureates used the fruit fly as a model system and built upon previous experiments that identified mutants with abnormal circadian rhythms. They isolated the gene responsible for the rhythm and conducted experiments to understand its function. They also discovered that the circadian clock operates through an auto regulatory self-sustained inhibitory feedback mechanism.

Q: Why is circadian rhythm important?

The circadian rhythm is important because it allows organisms to anticipate and adapt to the daily changes in conditions. It helps in being active during the day and enables other processes to take place during the night. Evolutionarily, it has provided an advantage in terms of being prepared and taking advantage of critical daylight hours.

Q: Is the circadian clock present in all cells?

Yes, the circadian clock is present in most cells of our body. It was previously known that there is a central clock in the brain, but the laureates' discoveries showed that it also exists in other parts of the body.

Q: Can you explain the mechanism of the circadian clock in simpler terms?

The circadian clock can be compared to an oscillator, like an hourglass. It builds up a substance that, when present, turns off its own production, creating an oscillation. This self-sustained, autonomous mechanism regulates the clock.

Q: What is the field of chronobiology and chrono medicine?

Chronobiology and chrono medicine are fields that explore the study of biological rhythms and their implications for health. They are rapidly expanding areas of research, but in humans, most evidence so far is based on correlations rather than firm evidence for the circadian clock's impact on specific diseases.

Q: Are there any known implications of the circadian clock on disease?

Sleep phase disorders, caused by mutations in core clock genes, are solid examples of the circadian clock's impact on disease. Jet lag, although not a disease itself, indicates that when our inner clock is misaligned with the environment, we feel bad. However, apart from these examples, most findings in humans are still correlations and require further research.

Q: How complex is the circadian clock's machinery?

The core machinery of the circadian clock is more complex than initially believed. There are interconnected loops, mechanisms for entrainment to adjust the clock, and output mechanisms that control other genes. The system is dynamic, and researchers are continuously learning more about its complexity.

Q: Who are the three Nobel laureates?

The three Nobel laureates in the field of circadian rhythm are Jeffrey C. Hall, Michael Rosbash, and Michael W. Young. They are all Americans and have made significant contributions to the understanding of the circadian clock mechanism.

Takeaways

The Nobel laureates' discoveries in the field of circadian rhythm have provided a molecular understanding of a fundamental biological mechanism. The circadian rhythm explains how living organisms adapt to the rotation of the Earth and anticipate daily changes. This discovery has opened up numerous questions and avenues for further research in chronobiology and chrono medicine. Understanding the circadian clock mechanism offers potential insights into the impact of lifestyle and misalignments on disease. Overall, the laureates' work has shed light on a crucial aspect of human biology.

Summary & Key Takeaways

• Circadian rhythm is the daily biological pattern that enables organisms to anticipate and adapt to the contrasting conditions of day and night. This internal timing system provides an evolutionary advantage by preparing organisms to be active, hunt, escape danger, hide, sleep, or perform other processes at appropriate times rather than simply reacting.

• The laureates used fruit flies and mutant strains with long, short, or absent rhythms. They isolated the gene associated with these variations and conducted sequential experiments to determine its function. Their work revealed an autonomous oscillator based on inhibitory feedback, in which an accumulating substance eventually turns off its own synthesis before production begins again.

• The basic clock mechanism operates in most cells, while a central clock in the brain helps control rhythms throughout the body. Research now examines interconnected regulatory loops, clock adjustment to environmental signals, synchronization among bodily clocks, and clock-controlled genes. Medical implications remain promising, although many proposed human disease relationships are still correlations.