Are You A Night Owl? We Are Closer to Knowing Why

A surprisingly common mutation causes this sleep disorder by changing a vital component of the biological clock that maintains the body’s daily rhythms.

Sleep shows up in several well-known films. In the 2010 Christopher Nolan heist film Inception, Leonardo DiCaprio stars as a thief who steals information by infiltrating individuals’ dreams and subconscious minds. Nolan based the movie on lucid dreaming, a state in which you are aware of your dreams and can exercise a modicum of control over them.

Have you seen the sci-fi film Eternal Sunshine of the Spotless Mind? The 2004 movie features Jim Carrey and Kate Winslet as star-crossed lovers. The two erase each other from their memory using the services of a fictional company. The procedure happens during sleep; Joel Barish, the Carrey character, spends much of the movie in a dream state as he has his memories erased.

Our inner clock: A brief history

During the 1700s, the astronomer Jean Jacques d’Ortous de Mairan studied mimosa plants. He found that the plant’s leaves would open towards the sun during the daytime but closed at dusk. But what if the plant lived only in darkness? The leaves continued to follow their regular daily oscillation, seeming to possess an internal biological clock.

Similar to the plants with which we live, we humans have a biological clock that adjusts our physiology throughout the day. You probably know this adaptation as the circadian rhythm, a descriptor derived from the Latin circa (“around”) and dies (“day”).

How does our internal circadian biological clock function? We have recently made additional strides in answering this question.

Our body has clock proteins

Earth’s life has adapted to the planet’s rotation. As is the case with other organisms, humans have an internal biological clock. This time regulator helps us adjust to the daily rhythms of living. But how does such a clock function?

Today, we turn to our body’s clock proteins involved in regulating our internal clock. First, a bit of history. In the 1970s, Seymour Benzer and his protege Ronald Konopka wondered if they could find the genes that regulate the circadian rhythms of fruit flies. They found success, demonstrating that mutations in a previously unknown gene messed up the flies’ circadian rhythm. They designated this gene period.

Fast forward to the work of Dr. Michael Young, based at Rockefeller University (New York City) and his colleagues Drs. Michael Rosbash and Michael Young of Brandeis University (USA). Their work elucidated the inner workings of our internal clock. This time regulator allows us to adapt our biological rhythms to different phases of day and night.

How does our body’s internal clock get its work done? Here’s how our 2020 Nobel Laureate’s earned their prize:

Drs. Hall, Rosbash, and Young studied fruit flies to figure out the internal clock. In 1984, they identified a gene that encodes a protein that builds up during the night but degrades during the day.

A self-regulating clockwork mechanism

The groundbreaking scientists identified other proteins in the clock mechanism that govern the self-sustaining clockwork within our cells. The internal clock affects changes in the activity of genes and proteins. There are four such entities:

  • The CLOCK and MAL1 proteins form a complex that turns on the other two clock proteins’ genes.
  • The other two clock proteins, period and cytochrome, combine to repress the activity of CLOCK/MAL1, turning themselves on and reinitiating the process.

And now, we come to our current research study. Researchers at The University of Texas Southwestern Medical Center (USA) recently reported their findings. They recognized that PER (the protein encoded by period) accumulates during the night and gets degraded during the day. PER levels oscillate over a 24-hour cycle, synchronizing with the circadian rhythm.

A small part of the protein’s tail is left out when there is a mutation in the cryptochrome gene. The new research found that this changes how tightly the cryptochrome binds to the CLOCK: BMAL1 complex.

In essence, the removed region controls the cryptochrome activity to lead to a 24-hour clock. If we did not have this snipping, cryptochrome binds more tightly and stretches out the clock’s length each day. How tightly it binds sets the clock speed!

Someday we may have drugs that fit into this pocket to alter our body’s clock. The current study authors are doing that work, testing molecules to see if they fit in the clock’s molecular pocket. Got a delayed sleep phase disorder? They may find an answer for you.

How does the circadian rhythm affect us?

Insights into our biological clock mechanism should lead to strategies for treating circadian rhythm and sleep disorders. Thank you for joining me today.


I have degrees from Harvard, Yale, and Penn. I am a radiation oncologist in the Seattle area. You may find me regularly posting at

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