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Taking Apart the Body's Clock

March/April 1998

Humans have always measured their existence with outward signs of the passage of time: day and night, sunrise and sunset, the ebb and flow of tides, the change of seasons. Not surprisingly, our internal clocks tend to match these natural cycles.

But today, the 24-hour workplace, frequent flights across time zones and our inability to sleep on cue are forcing researchers to take a closer look at our biological clocks. How does the body set up the clock? Which genes control it? How do they keep track of time, and how do they affect the rest of the body?

These and other questions are the focus of NSF's Science and Technology Center for Biological Timing at the University of Virginia in Charlottesville. Gene Block, Director of the Center, defines the Center's goal as "understanding the cellular and molecular mechanisms of the biological clock."

Geneticist Michael Young and his colleagues have taken the Center a long way towards achieving that goal. They study fruit flies because, like humans, fruit flies have a 24-hour or circadian body clock.

After successfully cloning one of the genes known to be involved in the biological clock, Young's group found a second gene in 1994. Only recently, however, was the story of the fly's body clock finally put together.


The two biological clock genes--named "per" for period and "tim" for timeless--become active in the fly's brain sometime around midday. The two genes begin to transcribe their DNA code into "per" and "tim" RNA molecules. At dusk, this RNA production peaks, and the cell begins to use the RNA to produce two proteins named PER and TIM.

Then, the two new proteins meet. "Part of the TIM protein binds to the PER protein," Young explains. "They enter the cell nucleus, a process that sets the time and duration of the circadian cycle."

Four hours before dawn, the scientists hypothesize, PER and TIM signal the nucleus to stop making RNA. They begin to disintegrate. By dawn, the proteins are gone and the cycle begins again.

The Center continues to make discoveries that refine our understanding of the biological clock. While all of Young's work so far has been done on flies, he believes the results correlate to the human body clock. "The outcome," says Block, "will be the eventual ability to control both the period and phase of biological clocks." That is, humans may find a way to control the body's 24-hour clock and its synchronization with other internal clocks (such as the reproductive cycle) or external clocks (such as the sun).

Benefits of this control could include alleviating jet lag or sleep disorders and assisting shift workers in remaining alert at night. This research may eventually offer a way to coordinate the demands of our activities with our biological rhythms so that we can always be working at our peak capacity.
[December 1996]

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