Keeping the body in sync -- The stability of cellular clocks

Mar 13, 2007

A study in Switzerland uses the tools of physics to show how our circadian clocks manage to keep accurate time in the noisy cellular environment.

In an article appearing March 13 in the journal Molecular Systems Biology, researchers from the Ecole Polytechnique Federale de Lausanne demonstrate that the stability of cellular oscillators depends on specific biochemical processes, reflecting recent association studies in families affected by advanced sleep phase syndrome.

Circadian rhythms are cyclical changes in physiology, gene expression, and behavior that run on a cycle of approximately one day, even in conditions of constant light or darkness. Peripheral organs in the body have their own cellular clocks that are reset on a daily basis by a central master clock in the brain. The operation of the cellular clocks is controlled by the coordinated action of a limited number of core clock genes. The oscillators work like this: the cell receives a signal from the master pacemaker in the hypothalamus, and then these clock genes respond by setting up concentration gradients that change in a periodic manner. The cell “interprets” these gradients and unleashes tissue-specific circadian responses. Some examples of output from these clocks are the daily rhythmic changes in body temperature, blood pressure, heart rate, concentrations of melatonin and glucocorticoids, urine production, acid secretion in the gastrointestinal tract, and changes in liver metabolism.

In the tiny volume of the cell, however, the chemical environment is constantly fluctuating. How is it possible for all these cell-autonomous clocks to sustain accurate 24-hour rhythms in such a noisy environment?

Using mouse fibroblast circadian bioluminescence recordings from the Schibler Lab at the University of Geneva, the researchers turned to dynamical systems theory and developed a mathematical model that identified the molecular parameters responsible for the stability of the cellular clocks. Stability is a measure of how fast the system reverts to its initial state after being perturbed.

“To my knowledge we are the first to discuss how the stability of the oscillator directly affects bioluminescence recordings,” explains Felix Naef, a systems biology professor at EPFL and the Swiss Institute for Experimental Cancer Research. “We found that the phosphorylation and transcription rates of a specific gene are key determinants of the stability of our internal body clocks.”

This result is consistent with recent research from the University of California, San Francisco involving families whose circadian clocks don’t tick quite right. These families’ clocks are shorter than 24 hours, and they also have mutations in oscillator-related genes. The current results shed light on how a genetically-linked phosphorylation event gone wrong could lead to inaccurate timing of our body clockworks.

Source: Ecole Polytechnique Fédérale de Lausanne

Explore further: Rare new species of plant: Stachys caroliniana

add to favorites email to friend print save as pdf

Related Stories

Atomic timekeeping, on the go

Nov 12, 2014

What time is it? The answer, no matter what your initial reference may be—a wristwatch, a smartphone, or an alarm clock—will always trace back to the atomic clock.

At the heart of the circadian clock

Jun 11, 2013

(Phys.org) —Cellular processes in most organisms are regulated by an internal clock, and proteins called cryptochromes are at the core of its central oscillator. The three dimensional structures of cryptochromes ...

Recommended for you

Rare new species of plant: Stachys caroliniana

Nov 21, 2014

The exclusive club of explorers who have discovered a rare new species of life isn't restricted to globetrotters traveling to remote locations like the Amazon rainforests, Madagascar or the woodlands of the ...

Mysterious glowworm found in Peruvian rainforest

Nov 21, 2014

(Phys.org) —Wildlife photographer Jeff Cremer has discovered what appears to be a new type of bioluminescent larvae. He told members of the press recently that he was walking near a camp in the Peruvian ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.