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Last Updated: Sunday, 9 July 2006, 00:19 GMT 01:19 UK
Doubt cast on body clock theory
Sleeping woman
Genes control sleep patterns
Assumptions about the way the first gene known to control the internal clock of the human body works have been turned on their head by US researchers.

The discovery means drug design for body clock disorders such as jet lag and insomnia may have to be rethought.

Researchers found a gene mutation called tau speeds up the body clock by increasing gene activity - rather than by decreasing it, as had been thought.

Details appear online in Proceedings of the National Academy of Sciences.

The key to developing treatments for problems like insomnia is being able to predict how the body's internal clock can be controlled
Dr David Virshup

The research was carried out by the University of Utah's Huntsman Cancer Institute and the University of Michigan, Ann Arbor.

Previous research had indicated that the tau mutation occurred in a gene called CK1 - and caused an 85% loss of activity in this gene.

This, it was thought, explained why the hamsters carrying the mutation had a short day, working on a 20-hour cycle instead of the usual 24-hours.

However, a computer simulation designed by mathematician Dr Daniel Forger cast doubt on this theory.

Dr Forger's simulation predicted that the shortening of the body clock was likely to be the result of the tau mutation increasing, rather than decreasing, CK1 activity.

Dr Forger's theory was put to the test by a team led by Dr David Virshup who examined the effect of a drug that inhibited CK1 on cultured rat cells.

They found that the cells had a longer day - suggesting Dr Forger was right.

Mouse cell tests

They next tested the effect of putting the normal or mutant CK1 genes into mouse cells, by measuring how quickly a protein, known to play a key role in setting the body clock, disappeared from the cells.

The faster the protein vanishes, the faster a cell's internal body clock will tick over.

The researchers found that the mutant version of CK1 cleared the protein more quickly - apparently proving that tau stimulates rather than inhibits CK1.

Dr Virshup said his team was now working on ways to monitor the tau effect on mice.

However, he said the findings so far cast doubt on the current received wisdom, and he said: "The key to developing treatments for problems like depression and insomnia - disorders influenced by circadian rhythm - is being able to predict how the body's internal clock can be controlled.

"If the working model is wrong, drugs will have the opposite effect."

Dr Neil Stanley, a sleep expert at the Human Psychopharmacology Research Unit at Surrey University, said there was still much to learn about the regulation of the human body clock.

He said: "Whilst we have made great progress in the last few years, sleep is still that mysterious third of our life."

Disruption of circadian rhythms has been linked to cancer and diabetes, as well as depression and sleep disorders.




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