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Circadian Clocks Triggered Chemical Reactions may Be Behind Jet Lag

Scientists from Cornell University and Dartmouth University have explained the biological mechanism by which circadian clocks, a factor responsible for why people get sleepy at night and wake in the morning, sense light through a process that transfers energy from light to chemical reactions in cells, which may be behind jet lag, mental illness, and even some forms of cancer in humans.

Circadian clocks in cells respond to differences in light between night and day and thereby allow organisms to anticipate changes in the environment by pacing their metabolism to this daily cycle. They affect many processes like setting timing when blooming plants open their petals in the morning and close them at night, or setting when fungi release spores to maximize their reproductive success.

"These clocks are highly conserved in all organisms, and in organisms separated by hundreds of millions of years of evolution," said Brian Crane, the paper's senior author and an Associate Professor in Cornell's Department of Chemistry and Chemical Biology.

During the study, the researchers focused on how a fungus uses circadian clock light sensors to control production of carotenoids, which protect against damage from the sun's ultraviolet radiation just after sunrise. They studied a protein called vivid, which contains a chromophore, a light-absorbing molecule.

The researchers say that the chromophore captures a particle of light, and the captured energy from the light triggers a series of interactions that ultimately lead to conformational changes on the surface of the vivid protein, causing a cascade of events affecting the expression of genes, such as turning carotenoid production on and off.

When they substituted a single atom (sulphur for oxygen) on the surface of the vivid protein, the chain of events shut down, preventing the structural changes on the protein's surface, as a result of which, the regulation of carot enoid production was disrupted.

"We can now show that this conformational change in the protein is directly related to its function in the organism," said Brian Zoltowski, the paper's lead author and a graduate student at Cornell in chemical biology.

The researchers believe that just like the circadian clock allows the fungus to regulate and produce carotenoids only when they are needed for protection against the sun's rays, a similar "switch" may be responsible for timing the sleep cycle in humans.

"We were interested in trying to understand behavior at the molecular level. This a great example of chemical biology, in that we can perturb the chemistry of a single molecule in a particular way and actually change the behavior of a complex organism," said Crane.

The study has been published in the journal Science.


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