(Press-News.org) Using an automated screening technique developed by pharmaceutical companies to find new drugs, a team of researchers from UC San Diego and three other research institutions has discovered a molecule with the most potent effects ever seen on the biological clock.
Dubbed by the scientists "longdaysin," for its ability to dramatically slow down the biological clock, the new compound and the application of their screening method to the discovery of other clock-shifting chemicals could pave the way for a host of new drugs to treat severe sleep disorders or quickly reset the biological clocks of jet-lagged travelers who regularly travel across multiple time zones.
"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."
The researchers demonstrated the dramatic effects of longdaysin by lengthening the biological clocks of larval zebra fish by more than 10 hours.
"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."
Biologists in Kay's laboratory and the nearby Genomics Institute of the Novartis Research Foundation, who were led by Tsuyoshi Hirota, the first author of the paper, discovered longdaysin by screening thousands of compounds with a chemical robot that tested the reaction of each compound with a line of human bone cancer cells that the researchers' genetically modified so that they could visually see changes in the cells' circadian rhythms. This was done by attaching in the cells a clock gene to a luciferase gene used by fireflies to glow at night, so that the cells glowed when the biological clock was activated. A chemical robot screened more than 120,000 potential compounds from a chemical library into individual micro-titer wells, a system used by drug companies called high-throughput screening, and automatically singled out those molecules found to have the biggest effects on the biological clock.
Once Kay's group had isolated longdaysin, it turned to biological chemists in Peter Schultz's laboratory at The Scripps Research Institute to characterize the molecule and figure out the mechanisms of how it lengthened the biological clock. That analysis showed that three separate protein kinases on the compound were responsible for the dramatic effect of longdaysin, one of which, CK1alpha, had previously been ignored by chronobiology researchers.
"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.
The researchers then showed that longdaysin had the same effect of lengthening the biological clock in mouse tissue samples and zebra fish larvae that carried luciferase genes attached to their clock genes.
"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."
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Other co-authors of the paper besides Hirota and Schultz were Warren Lewis, Eric Zhang, Ghislain Breton and David Traver of UCSD; Jae Wook Lee of TSRI; Xianzhong Liu, Michael Garcia Eric Peters of the Genomics Institute of the Novartis Research Foundation; and Pierre Etchegaray of the University of Massachusetts Medical School.
The study was funded by grants from the National Institutes of Health.
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Los Angeles, CA (December 15, 2010) Being a part of many different social groups can improve mental health and help a person cope with stressful events. It also leads to better physical health, making you more able to withstand—and recover faster from—physical challenges, according to a study in the current Social Psychological and Personality Science (published by SAGE).
Belonging to groups, such as networks of friends, family, clubs and sport teams, improves mental health because groups provide support, help you to feel good about yourself and keep you active. But ...
Los Angeles, CA (December 15, 2010) When computerized neuropsychological testing is used, high school athletes suffering from a sports-related concussion are less likely to be returned to play within one week of their injury, according to a study in The American Journal of Sports Medicine (published by SAGE). Unfortunately, concussed football players are less likely to have computerized neuropsychological testing than those participating in other sports.
A total of 544 concussions were recorded by the High School Reporting Information Online surveillance system during ...
ANCHORAGE, Alaska – Sea-ice habitats essential to polar bears would likely respond positively should more curbs be placed on global greenhouse gas emissions, according to a new modeling study published today in the journal, Nature.
The study, led by the U.S. Geological Survey, included university and other federal agency scientists. The research broke new ground in the "tipping point" debate in the scientific community by providing evidence that during this century there does not seem to be a tipping point at which sea-ice loss would become irreversible.
The report ...
Washington, D.C.—Scientists from all over the world are taking a second, more expansive, look at the car-sized asteroid that exploded over Sudan's Nubian Desert in 2008. Initial research was focused on classifying the meteorite fragments that were collected two to five months after they were strewn across the desert and tracked by NASA's Near Earth Object astronomical network. Now in a series of 20 papers for a special double issue of the journal Meteoritics and Planetary Science, published on December 15, researchers have expanded their work to demonstrate the diversity ...
A small area deep in the brain called the perirhinal cortex is critical for forming unconscious conceptual memories, researchers at the UC Davis Center for Mind and Brain have found.
The perirhinal cortex was thought to be involved, like the neighboring hippocampus, in "declarative" or conscious memories, but the new results show that the picture is more complex, said lead author Wei-chun Wang, a graduate student at UC Davis.
The results were published Dec. 9 in the journal Neuron.
We're all familiar with memories that rise from the unconscious mind. Imagine looking ...
Dolphins along coast of Argentina could experience a significant loss of genetic diversity because some of the animals that accidently die when tangled in fishing nets are related. According to a new genetic analysis published this week in the journal PLoS One, Franciscana dolphins that die as by-catch are more than a collection of random individuals: many are most likely mother-offspring pairs. This result, which suggests reduced genetic diversity and reproductive potential, could have significant implications for the conservation of small marine mammals.
"It has always ...
Polar bears were added to the threatened species list nearly three years ago when their icy habitat showed steady, precipitous decline because of a warming climate.
But it appears the Arctic icons aren't necessarily doomed after all, according to results of a study published in this week's issue of the journal Nature.
The findings indicate that there is no "tipping point" that would result in unstoppable loss of summer sea ice when greenhouse gas-driven warming rises above a certain threshold.
Scientists from several institutions, including the U.S. Geological Survey ...
New York, NY, December 15, 2010 – There is burgeoning public interest in possible wide-ranging health benefits from vitamin D, including cardiovascular health. In a study published in the December 2010 issue of The American Journal of Medicine, investigators found that there was no independent association between serum levels of vitamin D or parathyroid hormone and cardiovascular mortality in this prospective study, the first in a population of older community-dwelling adults with a low prevalence of vitamin D deficiency and a broad range of kidney function.
Researchers ...
Madison, WI DECEMBER 15, 2010 -- The manufacturing of nanomaterials has been steadily on the rise in the medical, industrial, and scientific fields. Nanomaterials are materials that are engineered to have dimensions less than 100 nanometers and have very unique properties as a result of their small size.
In a study funded by the U.S. Environmental Protection Agency, a team of scientists from the University of Kentucky determined that earthworms could absorb copper nanoparticles present in soil.
One crucial step in determining the uptake of nanomaterials was discerning ...
MADISON — It's one of the more frustrating parts of summer. You check the weather forecast, see nothing dramatic, and go hiking or biking. Then, four hours later, a thunderstorm appears out of nowhere and ruins your afternoon.
Thunderstorms can bring intense rain, hail, lightning and even tornadoes, but "predicting them a few hours out is one of the great problems of meteorology," says Chian-Yi Liu, a postdoctoral researcher at the University of Wisconsin-Madison.
And the consequences can be more serious than a rained-out hike — even major storms can be missed, Liu ...
