New Discovery About Biologic Clocks

A new study offers insight on a mutation in the gene that regulates circadian rhythm, causing scientists to change their approach in designing new drugs to treat sleep disorders, depression, jet lag, and other biologic clock disorders.

Researchers from the Huntsman Cancer Institute at the University of Utah (Salt Lake City, USA) and the University of Michigan (Ann Arbor, USA) examined the so-called tau mutation that causes hamsters to have a 20-hour day instead of a 24-hour day. The researchers discovered that what was previously believed about the tau mutation--that a decrease in gene activity sped up a mammal's internal clock--was incorrect, and that in fact, the opposite was true; the mutation caused an increase in gene activity to speed up the clock, making the day two to four hours shorter for affected animals. The study was published in the July 3, 2006, online edition of the Proceedings of the [U.S.]National Academy of Sciences.

Previous work had indicated that the tau mutation occurred in a gene called casein kinase 1 epsilon (CK1) and that the mutation caused an 85% loss of gene activity. A computer simulation by University of Michigan mathematician Daniel Forger, Ph.D., an assistant professor of mathematics, concluded that the mutant CK1 gene would cause PER, one of the proteins responsible for running the biologic clock, to dissipate more quickly, triggering a new day cycle. Upon trial, the model proved correct: the circadian rhythm within the mouse cells did speed up, explaining why a day for an animal with the tau mutation would last only 20 hours.

"The key to developing treatments for problems like depression and insomnia--disorders influenced by circadian rhythm--is being able to predict how the body's internal clock can be controlled,” said David Virshup, M.D., of the Huntsman Cancer Institute, co-principal investigator on the project. "If the working model is wrong, drugs will have the opposite effect.”

Biologic clocks with a circadian rhythm period of approximately 24 hours exist in most organisms and time a variety of functions, including sleep-wake cycles, hormone release, bioluminescence, and core body temperature fluctuations. Disruption of these circadian rhythms has been linked to cancer and diabetes, as well as depression and sleep disorders.




Related Links:
Huntsman Cancer Institute
University of Michigan