December 15, 2010

Compound Has Potent Effects On Biological Clock

By Kim McDonald, UC San Diego



"Theoretically, longdaysin or a compound like it could be used to correct sleep disorders such as the genetic disorder familial advanced sleep syndrome, which is characterized by a clock that's running too fast," said Steve Kay, dean of UCSD's Division of Biological Sciences, who headed the research team, which published its findings in the December 14 issue of the journal PLoS Biology. "A compound that makes the clock slow down or speed up can also be used to phase-shift the clock"”in other words, to bump or reset the hands of the clock. This would help your body catch up when it is jet lagged or reset it to a normal day-night cycle when it has been thrown out of phase by shift work."


"Longdaysin is the champion by far in how much it can move the clock," said Kay, whose laboratory at UCSD had found compounds in previous studies that could shift the biological clock by as much as several hours at most. "We were really surprised to find out how much you can slow down the biological clock with this compound and still have a clock that is running."



"Because this compound doesn't just hit one target, but multiple targets, it showed us that if you want to shift the biological clock in a major way you have to hit multiple kinases," said Kay.


"We were really encouraged to find that when we added longdaysin to these living zebra fish, we lengthened the biological clock and didn't see any obvious deleterious effects," said Kay. "They grow normally while they are exposed to this compound. That showed us that our high-throughput assay works and accurately predicts how the compound works on the biological clock of a living fish. The next thing to do is to try this in a mammalian system."

Kay's research team plans to test longdaysin on mice in the near future, but its goal isn't to develop longdaysin into a drug.

"Longdaysin is not as potent as we would like," he adds. "This will be a tool for research."



Citation: Hirota T, Lee JW, Lewis WG, Zhang EE, Breton G, et al. (2010) High-Throughput Chemical Screen Identifies a Novel Potent Modulator of Cellular Circadian Rhythms and Reveals CKIa as a Clock Regulatory Kinase. PLoS Biol 8(12): e1000559. doi:10.1371/journal.pbio.1000559


Image Caption: The researchers discovered longdaysin by screening thousands of compounds with a chemical robot. Credit: UC San Diego


On the Net: