Researchers have discovered a molecule with the most significant effects yet seen on the biological clock.
The researchers discovered the molecule, nicknamed “longdaysin,” using an automated screening technique first developed by pharmaceutical companies to find new drugs. The compound was found to drastically slow the biological clock.
The discovery opens the door to search for more clock-shifting chemicals that could eventually become drugs that could treat severe sleep disorders or simply reset the clock for jet-lagged long-haul travelers.
The finding was the work of scientists from the University of California San Diego, the Genomics Institute of the Novartis Research Foundation and the University of Massachusetts Medical School.
“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,” said Steve Kay, dean of UCSD’s Division of Biological Sciences, in a statement. “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.”
The challenge for chronobiology researchers is to extend the biological clock without stopping it completely.
In an experiment with larval zebra fish, the researchers were able to lengthen the animals’ biological clocks by more than 10 hours.
The technique with which longdaysin was discovered is rather novel. The researchers screened thousands of compounds with a chemical robot. The robot tested the reaction of each compound with a line of human bone cancer cells.
The researchers genetically modified the cancer cells so that they could literally see changes in the cells’ circadian rhythms. They accomplished this by adding to the cells a luciferase gene, the kind used by fireflies to glow at night.
In turn, the cells actually glowed when the biological clock was activated, making it easier for the robot to pick out.
After longdaysin was identified and isolated, analysis revealed that three separate protein kinases were responsible for the clock-slowing effect. One of them, CK1alpha, had previously been ignored by researchers.
The next step is to test the molecule in a mammal, most likely a mouse. For now, the molecule isn’t strong enough to work as a pill — but it’s a step in the right direction.
Their findings were published in the Dec. 14 issue of the journal PLoS Biology.
