U.S. researchers say they've made a discovery about the body's circadian rhythm that could suggest new treatments for jet lag, sleep disorders and other problems linked to our 24-hour body clocks.
The circadian rhythm influences almost all aspects of an organism's life -- it has been studied in creatures from humans and animals to plants and even in fungi and cyanobacteria-- and central to these "clocks" are biological oscillators and important proteins with a lifetime of around 24 hours.
Circadian rhythms adjust themselves under the influence of external cues in the environment, most commonly the light cycle of daytime and nighttime.
Because the period of the biological clocks matches the lifetime of the key proteins, scientists have long assumed the stability of the protein was the main determinant of the period length of these biological timekeepers.
However, it's not quite that simple, say researchers at Dartmouth College.
The clock proteins undergo a progressive and coordinated modification known as phosphorylation, which changes protein activity and structure, eventually ending in degradation and the clock "turning over" when the proteins disappear, with the cycle beginning again with the synthesis of new proteins.
"We all used to think the circadian cycle ended when the important clock protein was degraded," says Jay Dunlap, a professor of genetics and biochemistry, "and that period length was determined in large part by how stable those proteins were."
However, Dunlap and his research colleagues, including Luis Larrondo from the Pontificia Universidad Católica de Chile, discovered phosphorylation itself could be sufficient to alter the effectiveness of the protein in providing negative feedback to the oscillator.
Although protein degradation is the final result, it may be that the structure of the protein, rather than changes in its stability, is in fact the key determinant of clock speed, the scientists report in the journal Science.
"Surprisingly, we found that stability is not the key factor in period determination," Dunlap says. "Once [structure change through] phosphorylation has passed a certain point it doesn't matter whether or not the clock protein has degraded because at that point it is invisible to the clock machinery."
"The circadian clock influences our daily lives in more ways than we can count," he says, "and this work points to how the clock might be manipulated to improve health."
