A novel method to measure circadian cycles

September 26, 2005

Everyone knows morning people and late-night owls. The variation in individual circadian rhythms is an anecdotal as well as experimentally verified fact. But, until now, to systematically study circadian differences (and thereby hope to rout out the underlying genetic causes), scientists have had to rely on prolonged behavioural observation. To screen for and identify circadian rhythm variations in humans, the required period of lengthy observation is prohibitively costly and labor intensive.

Circumventing these technical limitations, Ueli Schibler and colleagues report in the open-access journal PLoS Biology a new method to measure circadian cycles in mammalian cells cultured from tissues other than the suprachiasmatic nucleus. The researchers took skin samples from humans and infected subsequently made tissue cultures with a virus engineered to report with a fluorescent signal when a certain host circadian rhythm gene was expressed. They found that their data jibed with the previously accepted length of the human circadian cycle: 24.5 hours. Because of the sensitivity of their method, Schibler and colleagues also confirmed that, for both humans and mice, circadian rhythms vary substantially between individuals. This suggests that the genetics of the circadian clock likewise varies between individuals.

Unlike an individual's true rhythm, a fibroblast cell culture's rhythm does not vary with changes in light exposure or sleep habits. The researchers point out that their method can expose differences in circadian rhythms; it does not, however, directly measure the signal from the central coordinator of circadian rhythms in the brain, the suprachiasmatic nucleus.

In the future, scientists may use the new method to screen large populations for genetically linked sleep disturbances such as advanced and delayed sleep phase syndromes. They may also use this test to hone in on the genetic mechanism responsible for such conditions. Outside the realm of medicine, future genetic studies of circadian rhythm may exploit the method developed by Schibler and colleagues to explore questions about the exact relationship between the suprachiasmatic nucleus and the circadian rhythms of cultured fibroblast cells. Just how does this brain structure coordinate genetic imperatives with environmental input including light fluctuations? And frequent fliers, bleary-eyed in foreign time zones, may get an answer to why waking up is hard to do.
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Citation : Brown SA, Fleury-Olela F, Nagoshi E, Hauser C, Juge C, et al. (2005) The period length of fibroblast circadian gene expression varies widely among human individuals. PLoS Biol 3(10): e338.

CONTACT: Ueli Schibler
University of Geneva
30, quai Ernest Ansermet
Geneva, Switzerland CH-1211
+41-22-702 61 75
+41-22-702 68 68 (fax)
Ueli.Schibler@molbio.unige.ch

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