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Biologist studies jet lag

Henry Gens | Wednesday, September 4, 2013

A study by a Notre Dame biologist suggests jet lag may be permanently grounded in the future. As part of a collaborative effort with scientists from the University of Oxford, Associate Professor of Biological Sciences Giles Duffield helped identify a promising target in the circadian cycle for the development of novel therapeutics to combat the common effects of jet lag. The study was published in Cell Journal on Aug. 29.

The target molecule, SIK1, is a protein kinase that was singled out for further study after exhaustive screens, Duffield said. 

“The original screen looked for roughly 100 genes that were switched on by light in the part of the brain that is the ‘master clock’ – the hypothalamus,” Duffield said. “We saw that this kinase, SIK1, was an interesting molecule. The fact that it is a kinase and that it had the potential to interact with molecular components that we have already established in the biological clock mechanism is why it became a primary target in the subsequent analysis.”

Duffield said the way the SIK1 protein kinase modulates the internal clock is different from previously researched kinases in the pathway. 

“There are other kinases that regulate the clock, but they tend to regulate the speed of the clock, making it longer or shorter,” he said. “This is actually working with the light system, and targeting SIK1 essentially ‘shifts’ the clock.”  

This particular property could be the key to producing a drug to ameliorate the negative effects of interrupted circadian rhythms, known together colloquially as jet lag, Duffield said. 

“I think that if a pharmaceutical therapeutic agent could be developed that would target SIK1, it would either deactivate it so it doesn’t phosphorylate its target or stop it being induced at some point in the pathway,” he said. “I think it’s very tangible that a therapeutic agent could be developed, unlike other compounds of the clock which are less likely to be good targets.”

Such a beneficial treatment could have a considerable impact on health, and not just for frequent flyers, he said.

“It’s not just travelers that suffer from this – anybody doing shift work is potentially undergoing the equivalent of jet lag on a weekly basis,” Duffield said. “And that’s the real problem because you’ve got 16 percent of the U.S. and European workforce doing shift work, and these people are essentially suffering from jet lag.”

Chronic health risks abound for the significant portion of the labor force employed in shift work, especially as individuals spend more time employed in these sectors, Duffield said.

“There are several studies indicating that the level of diabetes, metabolic syndromes, and obesity levels are higher in people doing shift work – removing all other factors,” he said.

Duffield said even individuals in areas other than formal shift work may be unwittingly suffering from chronic disruptions to their circadian cycle. 

“An example I like to make is that of married people with a family – they are probably not all on the same ‘shift’; they do different ‘shifts’ during the week and then during the weekend they corrupt their artificial ‘time-zones’ because they want to spend time with the family,” he said. “By the time Monday comes around they’re really out of whack, and they’re suffering from jet lag all over again.” 

Duffield said he thinks his project can help point the way toward a therapeutic treatment to benefit travelers and shift workers. 

“I actually think that this is far more tangible than anything we’ve had before, at least in the circadian system,” Duffield said.