such as "Introduction", "Conclusion"..etc
June 29, 2006 — Researchers at the
University of Pennsylvania School of Medicine have identified a new
protein required for the circadian response to light in fruit flies.
The discovery of this protein - named JET - brings investigators one
step closer to understanding the process by which the body’s internal
clock synchronizes to light. Understanding how light affects circadian
(24-hour) rhythms will likely open doors to future treatments of jetlag.
The body’s 24-hour clock controls a multitude of internal functions
such as periods of sleep and wakefulness, body temperature, and
metabolism. Although circadian function produces a stable rhythm in the
body, the biological clock will reset in response to light. The human
condition known as jet lag takes place during the period when the body
is attempting to resynchronize to the environmental light changes
brought on by travel, namely from one time zone to another.
A mutant fruit fly that possesses jetlag-like behaviors enabled
senior author Amita Sehgal, PhD, Professor of Neuroscience at Penn and
a Howard Hughes Medical Institute (HHMI) Investigator, and colleagues
to identify the gene and subsequent protein that aids in the response
of the internal biological clock to light. The researchers report their
findings in most recent issue of Science.
To test the circadian rhythm of fruit flies, Sehgal and others
exposed wild type (control) and mutant flies to several light and dark
settings - constant darkness, constant light, and equal periods of
light and darkness (a light-dark cycle). During exposure to constant
light for one week, the controls developed a disrupted sleep pattern
after a few days, while the mutants maintained a regular circadian
rhythm. The mutant and control flies displayed no behavioral
differences during their exposure to constant darkness and the
light-dark cycle. However, when the fruit flies were shifted from one
light-dark cycle to another, the mutant flies took two days longer to
adjust their sleep-wake cycle to the new light-dark schedule.
“The behavior of the mutant flies is similar to that displayed in a
person who has prolonged jetlag,” notes Sehgal. In search of answers to
the mutant’s defective circadian response to light, Sehgal and
colleagues looked to the molecular details of the clock cells in the
When a fruit fly is exposed to light, a photoreceptor called
cryptochrome (CRY) transduces the light signal and kicks off a series
of reactions within the clock cells of the brain. Under normal
conditions, CRY will respond to light by binding to a protein called
timeless (TIM). A second protein, a member of the F-box protein family,
also binds to TIM, signaling TIM for cellular destruction.
Genetic analysis revealed that the jetlag flies possess a mutation
in a gene that encodes a member of the F-box protein family. A closer
examination of the protein produced by the mutated sequence led
researchers to JET, a new protein within the F-box protein family.
“Since the degradation of TIM always happens in the presence of
light, the animal associates the absence of TIM with daytime hours,”
explains Sehgal. The mutated JET protein reduces the light-dependent
degradation of TIM and the circadian response to light.
Sehgal and others were able to reverse the behaviors in the jetlag
flies by genetically replacing the mutated gene sequence with the
normal sequence, which led to the production of the wild-type (control)
JET protein. When the jetlag flies acquired the normal JET protein,
regular TIM degradation took place and the fruit fly was better able to
adjust to shifts in the light-dark cycle.
Future studies in the Sehgal lab will focus on continuing to
identify other molecules required for the circadian response to light.
“Some of the molecules required for the circadian light response in
flies may be conserved in humans. Over time, we will have a better
understanding of how the human clock responds to light and may be able
to design drugs to treat jetlag,” concludes Sehgal.
Study co-authors are Kyunghee Koh and Xiangzhong Zheng, both from
Penn. These studies were funded by the National Institutes of Health
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