Researchers Unwind Secrets Of Biological Clocks

Even this lowly one-celled bacterium has a biological clock, the sophisticated internal timing device that governs the daily rhythms of people, animals and plants, says Susan Golden, a biology professor at Texas A&M University. The university’s Department of Biology is a leader in unraveling the mysteries of biological clocks, research that eventually could lead to cures for sleep and mood disorders, as well as other medical problems.

Golden and her colleagues also study the biological clocks of birds, rats and fungi, but it was the bacterium known as Synechococcus elongatus that yielded the latest revelation: the first structural model of part of the clockworks.

The researchers used magnetic-resonance imaging to limn the structure of one of the proteins produced by a trio of genes that function like the turning gears in a wristwatch. The protein in this microscopic “timing-input device” takes in and transmits environmental signals to adjust the clock for seasonal changes in day and night, according to the model, published recently in Proceedings of the National Academy of Science.

Although scientists do not know whether the same genetic scheme also pertains to biological clocks in people, Golden said, revealing the structural diagram is “a very important step” to learning how the clocks actually work.

It was no small trick to produce a model from a one-celled organism so simple that no one can even see just how it acts out its daily rhythms of life.

The organism doesn’t even have a nucleus, after all, much less a discernable daily routine. So Golden, a molecular biologist who has devised ways to genetically manipulate Synechococcus, rigged a sample with a tiny “light meter” that reflected daily changes inside the organism. She used luciferase, the same enzyme that illuminates fireflies, to make a “reporter gene” that literally shed light on its rhythms. “It tells us what the clock is doing,” Golden said.

The magnetic-resonance imaging work that helped to reveal the three-dimensional structure was performed in the laboratory of Andy LiWang, an assistant professor of biochemistry and biophysics at Texas A&M. Related research on the two other genes in the trio that make up the timing device (i.e., just the part we have structure for has an input role, but all three are main gears of the clock) was conducted at Vanderbilt University and Nagoya University in Japan.

Researchers at Texas A&M, including students, are continuing to test genes in Synechococcus to see what others might also make up the biological clock, Golden said.