The new findings in bacteria promise to help discover new drugs for humans to treat such conditions as jet lag and sleep disorders, the scientists said. Such pills someday also could help keep people working late shifts from getting drowsy.
"Such medication could really help reduce industrial accidents like those at Three Mile Island and Chernobyl, where alertness or lack thereof might really have played a role," researcher Carl Johnson, a biologist at Vanderbilt University in Nashville, told United Press International.
Discoveries on how to rework biological clocks also could help farmers, Johnson explained. Treatments that tinker with plant timers "could suppress plants from flowering too soon, enhancing leafy production. This would help with crops like basil."
In humans, biological clocks run the wake-sleep cycle and influence fundamentals of life such as body temperature. When a person's clock is out of sync with the environment, the condition known as jet lag results. Plants have biological clocks too, measuring day and night to determine the time of year to control seasonal flowering.
For years, no one thought bacteria had biological clocks, however, because microbes typically reproduce in less than 24 hours, becoming whole new life forms in the process. But Taiwanese scientists accidentally discovered otherwise in green pond scum in rice paddies.
Cyanobacteria, or blue-green algae, remove nitrogen from the air and affix it chemically so plants can use it as a nutrient. Photosynthesis and nitrogen fixation are biochemically incompatible, and the researchers found the germs solved this problem by saving nitrogen fixation for after dark.
"When those of us who work in biological clocks saw their results, we realized that the algae must have a clock," Johnson said. Although the researchers suspect the bacterial clock is quite different from those in humans and plants, he said discoveries in how one work already have helped understand how the others operate.
As reported in the Dec. 2 online version of the Proceedings of the National Academy of Sciences, Johnson and colleagues from Texas A&M University and the University of Nagoya in Japan previously had sequenced genes that code for three critical clock proteins -- KaiA, KaiB and KaiC. The team now has visualized the structure of KaiC, the largest of the three proteins.
"This is exciting because this is the first time structural information on a clock protein was shown," physiologist Yi Liu of the University of Texas Southwestern Medical Center at Dallas said.
Electron microscopy has revealed the clockwork protein even looks cog-like, with a shape like a hexagonal ring. "It looks a little like a bulbous doughnut," Johnson said. The shape is similar to other proteins that act on DNA. "DNA can thread through the middle of ring-structure proteins like this," Johnson said.
The researchers confirmed KaiC binds to DNA. Johnson speculates the protein unwinds the bundles of DNA that make up the bacterium's chromosome, exposing it to cellular machinery so the microbe can express genes. He said they now plan to find out how KaiC is structured molecularly, to know what "causes the clock to run faster or slower or stop entirely in mutations."
The rough picture Johnson's team currently has from electron microscopy is not detailed enough to understand how exactly KaiC binds to DNA, Liu explained.
"This goes together very well with work from other labs that will give us a total picture of a clock complex that keeps time," molecular biologist Susan Golden of Texas A&M University in College Station told UPI. "We want to integrate all that information on how the proteins interact as quickly as we can to get a view of the whole clock, kind of like taking the back off a pocket watch to look at all the gears."
Golden's team also reports in the Proceedings of the National Academy of Sciences to have solved half the molecular structure of KaiA. She explains KaiB, the littlest of the three proteins, remains hard to investigate because nothing from its molecular sequence yet provides a clue as to how it works.
(Reported by Charles Choi, UPI Science News, in New York)
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