Experiments illuminate workings of biological clocks

September 10, 1999 -- By zapping fruit flies with light pulses and analyzing the biochemical consequences, investigators from the Howard Hughes Medical Institute (HHMI) at the University of Pennsylvania have pinpointed how light resets the flies' biological clock.

Since such clocks occur in humans as well as flies, these insights could suggest new ways to treat jet lag or depression, which are thought to be influenced by circadian rhythms. These types of studies may also eventually help optimize drug treatments affected by the rhythmic changes in the human body's hormone levels.

In the September 10, 1999, issue of the journal Science, HHMI investigator Amita Sehgal and colleagues at the University of Pennsylvania School of Medicine show how light causes cells to break down a key biological clock protein called "timeless."

Biological, or circadian, clocks operate on a roughly 24-hour cycle that governs such functions as sleeping and waking, rest and activity, fluid balance, body temperature, cardiac output, oxygen consumption and endocrine gland secretion.

In previous studies, Sehgal and others had shown that the amount of the timeless protein (TIM) present in a fly's brain is a key signal that helps to synchronize the biological to the day-night cycle. In their current work, the HHMI team was able to demonstrate the biochemical mechanism that reduces levels of TIM, a key to clock synchrony.

Light itself doesn't directly reset the clock. Rather, light strikes photoreceptors in a fly's body, which then send signals to the clock. These signals somehow reduce levels of TIM. When the level of TIM reaches a low point, the timeless gene, TIM, is switched on to replenish TIM's levels and reset the biological clock.

While conducting earlier studies on timeless, Sehgal hypothesized that cell structures called proteasomes played a key role

Contact: Jim Keeley
Howard Hughes Medical Institute

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