How Earth's 24-hour Day-Night Cycle is Synchronized at the Cellular Level

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When a returning back to California from a trip to Japan or when waking up early after a long night of partying, the circadian rhythm is thrown off. This 24-hour day-night cycle has been genetically ingrained at the cellular level. The circadian rhythm has been widely observed in plants, animals, fungi, bacteria, and of course, humans. The primary external stimulus to this process is daylight. But how molecular clocks synchronize to the Earth's movement has been a mystery up to this point. A new study from the University of California (UC), San Diego shines a light on this important biological process. Researchers embedded a fluorescent protein in E. coli bacteria that glows when the biological clock oscillates.

When a returning back to California from a trip to Japan or when waking up early after a long night of partying, the circadian rhythm is thrown off. This 24-hour day-night cycle has been genetically ingrained at the cellular level. The circadian rhythm has been widely observed in plants, animals, fungi, bacteria, and of course, humans. The primary external stimulus to this process is daylight. But how molecular clocks synchronize to the Earth's movement has been a mystery up to this point. A new study from the University of California (UC), San Diego shines a light on this important biological process. Researchers embedded a fluorescent protein in E. coli bacteria that glows when the biological clock oscillates.

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All organisms naturally have a circadian rhythm, but it can be adjusted, or entrained, by the environment. That is why we are originally jet-lagged when flying to another part of the world, but can eventually adjust to the local time. Our circadian rhythm tells us when we should sleep and when we should eat. It affects our core body temperature, brain wave activities, and other body functions. Even if locked in a windowless room for many days, our circadian rhythm can still function for a time, although increasingly less accurate due to a lack of environmental cues.

How exactly the circadian process is performed by cells and populations of cells has remained a mystery. Biologists at UC San Diego created a model biological system using glowing fluorescent E. coli bacteria to see how the cells synchronize their internal clocks with the rotation of the Earth.

"The cells in our bodies are entrained, or synchronized, by light and would drift out of phase if not for sunlight," said Jeff Hasty, a professor of biology and bioengineering at UC San Diego who headed the research team. "But understanding the phenomenon of entrainment has been difficult because it's difficult to make measurements. The dynamics of the process involve many components and it's tricky to precisely characterize how it works. Synthetic biology provides an excellent tool for reducing the complexity of such systems in order to quantitatively understand them from the ground up. It's reductionism at its finest."

Hasty's team combined techniques from synthetic biology, microfluidic technology, and computational modeling to construct a microfluidic chip. This chip contained a series of chambers filled with E. coli bacteria. The genetic machinery tied to the circadian rhythm were connected with a green fluorescent protein. The chemical which triggers the internal clock mechanism, arabinose, was then flushed through the microfluidic chip to synthesize the 24-hour cycle in a matter of minutes. Changes in the circadian rhythm of the cells could be seen in fluorescent green.

This study has helped explain how the circadian cycle works at the cellular level. Future applications may include medical treatment for patients with sleep disorders and even diabetes. These afflictions have been found to be connected with problems with the biological clock.

The UC San Diego study has been published in the journal, Science.

Link to published article: http://www.sciencemag.org/content/333/6047/1315.abstract