Katherine Sharkey MD, Ph.D.

Feeling the Rhythm

And the Nobel Prize Goes to…Circadian Rhythms

5 reasons why circadian rhythms research is so crucial to scientific progress.

Posted Oct 21, 2017

Image created by Alex Callahan
Source: Image created by Alex Callahan

Circadian rhythms scientists and clinicians have a reason to be excited: On October 2, 2017, Jeffrey Hall and Michael Rosbash of Brandeis University and Michael W. Young of the Rockefeller University were awarded the 2017 Nobel Prize in Physiology or Medicine for their contributions to discoveries related to biological clocks and circadian rhythms. Beginning about three decades ago, these scientists began to unravel the inner workings of the biological clocks that keep us synchronized to the 24-hour day. Circadian rhythms play a critical role in health and well-being; this blog will explore many aspects of circadian rhythms and sleep as they relate to the human experience.

To start, here are five reasons why the work of Hall, Rosbash, and Young and its recognition by the Nobel Assembly of the Karolinska Institute are so important.

1. Our internal circadian rhythms help us adapt to life on Earth.

Circadian rhythms of physiology and behavior evolved so that the right things happen during the day and at night. Animals (including humans), plants, and even single-celled organisms like algae have internal biological clocks that allow them to take advantage of the environment. As the Earth proceeds with its 24-hour rotation around the sun, living conditions change drastically, particularly with respect to light and temperature. These predictable, cyclic changes can mean the difference between life and death: A mouse skittering through the forest at night can gather food safely, but the same mouse venturing out during the day becomes the food instead. Circadian rhythms allow our bodies to unconsciously anticipate environmental fluctuations across the day so that our underlying body and brain processes are optimized. From nutrition, feeding, and hormone secretion to mood regulation, alertness, and cognition, circadian rhythms regulate, organize, and coordinate all our daily functioning to fit Earth's 24-hour solar day.

2. Discovery of circadian clock mechanisms is a major genetic breakthrough.

One reason that Hall, Rosbash, and Young are being celebrated is because they sequenced the gene we call period. It was hypothesized for years that individual differences in rest-activity cycles were probably caused by genetics, but these Nobel laureates were able to find the exact location of this very important circadian gene and describe it in detail. Their work allowed the gene to be manipulated, deleted, and switched around so that its properties could be fully understood. In this way, their contribution added significantly to our understanding of genetic control of behavior.

3. Virtually every cell in our body has its own clock.

Circadian behavior and physiology are guided by the master clock in the hypothalamus area of the brain—the suprachiasmatic nucleus, aka the SCN. For many years, it was believed that the SCN had full control over circadian rhythms throughout the body, but we now know, in part through the molecular mechanisms revealed by the Nobel-winning scientists’ work, that every cell has the machinery to keep time. Each individual cell has the capability of generating a self-sustaining feedback loop that acts as a clock. Put simply, when the period gene turns on, the period protein, called PER, is manufactured. When enough PER builds up and binds with another protein, the period gene is turned off. The PER protein breaks down over time, and with the help of other circadian genes, the accumulation of the breakdown products turns the period gene back on again.The whole cycle takes about 24 hours, and voila, you have a molecular clock inside each cell throughout the body. The SCN in the brain is still the main clock, but it acts like an orchestra conductor, managing countless clocks throughout the body to stay coordinated across the day.

4. Fruit flies helped them figure it out.

When they are circling the ripe bananas in your kitchen, fruit flies get a bad rap. But these little critters, also known by their scientific name, Drosophila melanogaster, provide a wealth of information to scientists eager to learn more about the genetic origins of behavior. It turns out that the majority of human genes have a homolog in Drosophila. In other words, for most human genes, there is a gene in fruit flies that is similar in structure and evolutionary origin. And the great thing is that fruit flies are easier to study than people: They reproduce quickly and have short lifespans, so drosophila researchers can do breeding experiments and study multiple generations over a short period of time. This high-throughput research has allowed the Nobel scientists and their colleagues, like Amita Seghal of the University of Pennsylvania and Ravi Allada of Northwestern University, to make great progress in our understanding of the molecular and cellular networks that underlie circadian rhythms and sleep. Discoveries in the flies can then be reexamined in humans. Hard to believe those pesky flies have contributed so much to our knowledge of genetics.

5. The possibilities are endless.

The acknowledgment of circadian rhythms research by the Karolinska Institute and the Nobel Assembly helps cement the place of circadian rhythms research in the big leagues of science. Major medical conditions such as cancer, psychiatric illness, and obesity and other metabolic disorders like diabetes are influenced by the circadian clock. Ongoing research into clinical applications like stabilizing circadian rhythms to treat anxiety and depression or administering chemotherapy according to an individual’s circadian rhythms will be bolstered by the award. And this is why circadian rhythms scientists and researchers are walking tall now: Shining the spotlight on circadian science and the accomplishments of Hall, Robash, and Young should further propel the field toward new discoveries that will improve health and quality of life.