Scientists picking apart the inner workings of the biological clocks that govern the daily cycles of life have now identified several key cogs of the machinery and have shown that these main parts are remarkably similar between invertebrates and mammals.

In the June 5 issue of Science, one team describes the working parts that drive the clock in mice forward like a watch spring, and in another paper another team for the first time identifies the gene in fruit flies that corresponds to the mammalian Clock gene and shows how it can turn itself off again, enabling it to oscillate like a pendulum.

"We always thought that circadian clocks might work the same way in different organisms, but this is really the first evidence -- with the same genes playing the same role in flies and mice," says Joseph S. Takahashi, professor of neurobiology and physiology at Northwestern University, who is an author on both papers and last year was the first to clone the mammalian clock gene.

"We now have three different circadian clock genes that are conserved between insects and mammals," Takahashi said. "These genes define a surprisingly simple and elegant feedback loop of gene activation and inhibition that composes the core mechanism of the clock in animals."

In the first paper, Charles Weitz and coworkers at Harvard Medical School, with Takahashi's group at Northwestern, searched for and identified a protein molecule that can bind to the protein, CLOCK, produced by the mouse Clock gene. This protein molecule, called BMAL1, is produced at the same time and in the same regions of the brain as the CLOCK protein.

The CLOCK-BMAL1 pair, they showed, is capable of binding to and turning on a genetic switch that regulates another gene, which is called mper-1 because it is the mammalian version of the period gene, which is required for circadian rhythm in flies.

"We think this 'on' mechanism accounts for the positive compone
'"/>

Contact: Bill Burton
b-burton@nwu.edu
847-491-3115
Northwestern University
5-Jun-1998