Glowing, Blinking Bacteria Reveal How Cells Synchronize Biological Clocks

Glowing, Blinking Bacteria Reveal How Cells Synchronize Biological Clocks

  5:17:00 PM    Science Lover

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Biologists have long known that organisms from bacteria to humans use the 24 hour cycle of light and darkness to set their biological clocks. But exactly how these clocks are synchronized at the molecular level to perform the interactions within a population of cells that depend on the precise timing of circadian rhythms is less well understood.

Green fluorescent protein causes the E. coli to glow 
when the cells' clock is activated. (Credit: UC San Diego)

To better understand that process, biologists and bioengineers at UC San Diego created a model biological system consisting of glowing, blinking E. coli bacteria. This simple circadian system, the researchers report in the September 2 issue of Science, allowed them to study in detail how a population of cells synchronizes their biological clocks and enabled the researchers for the first time to describe this process mathematically.

"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."

To study the process of entrainment at the genetic level, Hasty and his team of researchers at UC San Diego's Biocircuits Institute combined techniques from synthetic biology, microfluidic technology and computational modeling to build a microfluidic chip with a series of chambers containing populations of E. coli bacteria. Within each bacterium, the genetic machinery responsible for the biological clock oscillations was tied to green fluorescent protein, which caused the bacteria to periodically fluoresce.



To simulate day and night cycles, the researchers modified the bacteria to glow and blink whenever arabinose -- a chemical that triggered the oscillatory clock mechanisms of the bacteria -- was flushed through the microfluidic chip. In this way, the scientists were able to simulate periodic day-night cycles over a period of only minutes instead of days to better understand how a population of cells synchronizes its biological clocks.

Hasty said a similar microfluidic system in principal could be constructed with mammalian cells to study how human cells synchronize with light and darkness. Such genetic model systems would have important future applications since scientists have discovered that problems with the biological clock can result in many common medical problems from diabetes to sleep disorders.

Other members of Hasty's team included Lev Tsimring, associate director of the BioCircuits Institute, and bioengineering graduate students Octavio Mondragon, Tal Danino and Jangir Selimkhanov. Their research was supported by grants from the National Institutes of Health and General Medicine and the San Diego Center for Systems Biology.

Story Source: The above story is reprinted (with editorial adaptations) from materials provided by University of California - San Diego.

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That Late-night Snack: Worse Than You Think

That Late-night Snack: Worse Than You Think

  9:12:00 PM    Science Lover

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Eat less, exercise more. Now there is new evidence to support adding another "must" to the weight-loss mantra: eat at the right time of day.

Eating at irregular times -- the equivalent of the middle of the night for humans,
when the body wants to sleep -- influences weight gain, a new study has found.
(Credit: iStockphoto/Curt Pickens)

A Northwestern University study has found that eating at irregular times -- the equivalent of the middle of the night for humans, when the body wants to sleep -- influences weight gain. The regulation of energy by the body's circadian rhythms may play a significant role. The study is the first causal evidence linking meal timing and increased weight gain.

"How or why a person gains weight is very complicated, but it clearly is not just calories in and calories out," said Fred Turek, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences and director of the Center for Sleep and Circadian Biology. "We think some factors are under circadian control. Better timing of meals, which would require a change in behavior, could be a critical element in slowing the ever-increasing incidence of obesity."

The findings could have implications for developing strategies to combat obesity in humans, as the United States and the world battle what has been called an "obesity epidemic." More than 300 million adults worldwide are obese, including more than a third of American adults.

Details of the obesity study, which was led by Turek, will be published online Sept. 3 by the journal Obesity.

"One of our research interests is shift workers, who tend to be overweight," said lead author Deanna M. Arble, a doctoral student in Turek's lab. "Their schedules force them to eat at times that conflict with their natural body rhythms. This was one piece of evidence that got us thinking -- eating at the wrong time of day might be contributing to weight gain. So we started our investigation with this experiment."

Simply modifying the time of feeding alone can greatly affect body weight, the researchers found. Mice that were fed a high-fat diet during normal sleeping hours gained significantly more weight (a 48 percent weight increase over their baseline) than mice eating the same type and amount of food during naturally wakeful hours (a 20 percent increase over their baseline). There was no statistical difference between the two groups regarding caloric intake or the amount of activity.

Over a period of six weeks, both groups of mice were allowed to eat as much high-fat diet as they wanted during their daily 12-hour feeding phase. (Much like many humans, mice have a preference for high-fat food.) Since mice are nocturnal, the 12-hour feeding phase was during the day for those fed during normal sleeping hours and during the night for those fed during naturally wakeful hours. Food was not provided during the other 12 hours of their day.

Our circadian clock, or biological timing system, governs our daily cycles of feeding, activity and sleep, with respect to external dark and light cycles. Recent studies have found the body's internal clock also regulates energy use, suggesting the timing of meals may matter in the balance between caloric intake and expenditure.

The researchers next plan to investigate the molecular mechanisms behind their observation that eating at the "wrong" time can lead to weight gain.

In addition to Turek and Arble, other authors of the paper are Joseph Bass, Aaron D. Laposky and Martha H. Vitaterna, all from Northwestern.

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