Research Reveals How Cells Tell Time

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The study was supported by the National Institutes of Health and the Welch

Foundation.

Released: Mon 08-Jun-2009, 11:10 ET

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http://www.newswise.com/articles/view/553144/?sc=rssn

Research Reveals How Cells Tell Time

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Science News Keywords

DR. YI LIU, BODY CLOCK, CIRCADIAN RHYTHMS, MOLD, FRQ, FUNGUS, NEUROSPORA, SLEEP

DISORDERS, BIOLOGICAL CLOCK, CELL PROTEIN, PHOSPHATE SITES, ENZYMES, UT

SOUTHWESTERN MEDICAL CENTER

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Description

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.

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UT Southwestern Medical Center

Dr. Yi Liu is studying mold that uses a protein called FRQ as the main gear of

its biological clock. His research team had found that a sequence of changes in

the protein's chemical structure is used to mark time, a finding that might

someday help develop treatments for human sleep disorders.

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Newswise — 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.

" This is an extremely high number, " Dr. Liu said. " Most proteins are controlled

by only a handful of phosphate sites. "

They also studied how these phosphates are added to FRQ daily and found that two

enzymes are responsible for adding most of the phosphate groups in

<em>Neurospora</em>. They also found that the total number of phosphates

oscillates robustly day by day.

In addition, the researchers created a series of mutations in many of the

phosphate docking sites, creating strains of mold that had abnormally short or

long daily clocks.

In upcoming studies, the researchers plan to identify which enzymes add

phosphates to specific sites and exactly how changes in a particular site affect

a cell's clock.

Other UT Southwestern physiology researchers contributing to the work were

co-lead authors Dr. Chi-Tai Tang, postdoctoral researcher, and Dr. Shaojie Li,

former postdoctoral researcher; Dr. Joonseok Cha, postdoctoral fellow; Dr.

Guocun Huang, assistant instructor; and Dr. Lily Li, former postdoctoral

researcher. Researchers from the National Institute of Biological Sciences in

China and the Chinese Academy of Sciences also participated.

The study was supported by the National Institutes of Health and the Welch

Foundation.

Visit www.utsouthwestern.org/sleep to learn more about UT Southwestern's

clinical services in sleep and breathing disorders.

Dr. Yi Liu --

http://www.utsouthwestern.edu/findfac/professional/0,2356,42920,00.html