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

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

Related stories:

Researchers figure out what makes a simple biological clock tick
An interdisciplinary team of researchers at Vanderbilt University has analyzed the simplest known biological clock and figured out what makes it tick. The results of their analysis are published in the March 27 issue of the journal Public Library of Science Biology.
Interdisciplinary volume on biological rhythms serves as both primer and in-depth resource
A variety of organisms—from bacteria and fungi to plants and animals—have biological rhythms, where the timing and duration of fundamental biological processes is naturally adjusted to allow them to adapt and survive, even under fluctuating environmental conditions. In recent years, significant advances have been made to understand the molecular basis of these rhythms and how they translate into modifications in cellular physiology and organismal behavior.
Keeping cells youthful: How telomere-building proteins get drawn into the fold
It may take just one or two proteins to polish off a simple cellular task, but life-or-death matters, such as caring for the ends of chromosomes known as telomeres, require interacting crews of proteins, all with a common goal but each with a specialized task.
Circadian rhythm-metabolism link discovered
UC Irvine researchers have found a molecular link between circadian rhythms – our own body clock – and metabolism. The discovery reveals new possibilities for the treatment of diabetes, obesity and other related diseases.
Scientists First To Measure Force Required To Move Individual Atoms
IBM scientists, in collaboration with the University of Regensburg in Germany, are the first ever to measure the force it takes to move individual atoms on a surface. This fundamental measurement provides important information for designing future atomic-scale devices: computer chips, miniaturized storage devices, and more.
Collaboration helps make JILA strontium atomic clock 'best in class'
A next-generation atomic clock that tops previous records for accuracy in clocks based on neutral atoms has been demonstrated by physicists at JILA, a joint institute of the Commerce Department's National Institute of Standards and Technology and the University of Colorado at Boulder. The new clock, based on thousands of strontium atoms trapped in grids of laser light, surpasses the accuracy of the current U.S. time standard based on a "fountain" of cesium atoms.
Optical Atomic Clock: A long look at the captured atoms
Optical clocks might become the atomic clocks of the future. Their "pendulum", i.e. the regular oscillation process which each clock needs, is an oscillation in the range of the visible light. As its frequency is higher than that of the microwave oscillations of the cesium atomic clocks, physicists expect another increase in the accuracy, stability and reliability.
New research alters concept of how circadian clock functions
Scientists from the University of Cambridge have identified a molecule that may govern how the circadian clock in plants responds to environmental changes.

News discussion:

General Science news