Research shows how cells tell time

Published on June 8, 2009 at 10:48 PM · No Comments

The fuzzy pale mold that lines the glass tubes in Dr. Yi Liu's lab doesn't look much like a clock.

But this fungus has an internal, cell-based timekeeper nearly as sophisticated as a human's, allowing UT Southwestern Medical Center physiologists to study easily the biochemistry and genetics of body clocks, or circadian rhythms.

In a new study appearing online this week in the Proceedings of the National Academy of Sciences, Dr. Liu and his co-workers have found that this mold, which uses a protein called FRQ as the main gear of its clock, marks time by a sequence of changes in the protein's chemical structure.

Dr. Liu said the new finding might someday help researchers develop treatments for human sleep disorders and other problems associated with a faulty biological clock.

"This timekeeping protein is really the core component of the circadian clock," said Dr. Liu, professor of physiology at UT Southwestern and senior author of the study.

Despite the evolutionary distance from mold to man, mechanisms controlling their circadian clocks are very similar. In both, circadian rhythms control many biological processes, including cell division, hormonal release, sleep/wake cycles, body temperature and brain activity.

The researchers employed a fungus called Neurospora, an organism frequently used in studies on genetics and cell processes, especially circadian rhythms. It reproduces in the dark and rests in the light.

A decade ago, Dr. Liu discovered that FRQ controlled the cellular clock in Neurospora by chemical changes of its protein structure. As the day goes on, the cell adds chemical bits called phosphates to the protein. Each new phosphate acts like a clock's ticking, letting the cell know that more time has passed.

When the number of phosphates added to FRQ reaches a certain threshold, the cell breaks it down, ready to start the cycle again.

The researchers, however, did not know where the phosphates attached to FRQ, how many got added throughout a day, or how they affected the protein's ability to "tell" time.

In the current study, the researchers used purified FRQ to analyze the specific sites where phosphate groups attach. In all, the researchers found 76 phosphate docking sites.

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