Discovery Could Help Millions

UMKC Police Officer Boyd Breedlove works evening shifts. Photo credit: Janet Rogers, Division of Strategic Marketing and Communications

School of Biological Sciences researchers find targets to enhance sleep/wake behaviors

Those who work evening shifts – including police officers, hospital workers and manufacturers – suffer much higher rates of health problems such as heart attack and stroke. University of Missouri-Kansas City School of Biological Sciences researchers have made a discovery that could improve the lives of millions of Americans who work outside of the normal 9-5 day.

In the laboratory, UMKC collaborators found a novel class of proteins that are potential drug targets to improve sleep/wake behaviors. Their findings were published in a recent issue of Neuron, one of the most influential neuroscience journals.

“This is the most important discovery of my UMKC career because it could help so many people,” said Jeffrey Price, a UMKC associate professor of biology. “Not only does this have the potential to affect shift workers, it could improve the function of people as they age or those with neurodegenerative diseases and the blind.”

Price authored the study with Associate Professor Samuel Bouyain; Research Associate Professor Andrew Keightley, Research Assistant Professor Jin-Yuan Fan; and graduate students Boadi Agyekum and Anandakrishnan Venkatesan. The work was multidisciplinary, employing genetics, biochemistry, cell biology, structural biology and proteomics.

“This was a complicated collaboration among three labs over several years,” said Bouyain, who is the head of an X-ray crystallography lab and determined the new protein’s structure. “The parts wouldn’t have made sense on their own.”

Fan’s and Price’s research expertise centers on circadian rhythms, individuals’ 24-hour schedules influenced mainly by light. The study was conducted with fruit flies, whose sleep cycles are similar to humans.

The new protein discovered by the UMKC team has been named Bride of Doubletime. The researchers found it can bind to another already well-known protein, Doubletime (earlier in his career, Price was one of the researchers who discovered that protein). That husband-and-wife-type binding is important because it adds phosphate groups to proteins, altering the body’s internal clock. So evening employees could work with similar wakefulness as when it’s naturally light, if the Doubletime/Bride of Doubletime pair could be targeted by drugs to alter the pace or settings of the internal clock. In a similar way, drugs target a relative of Bride of Doubletime paired with another protein to suppress immune function during organ transplants, so that the organs are not rejected by the body.

About 15 million Americans work on evening, overnight or rotating shifts, according to the U.S. Bureau of Labor Statistics. Industries including health care, public safety, transportation, news media, shipping and manufacturing operate 24-7.

Health researchers have long known that shift work — regularly working outside of normal daylight hours — disrupts the body’s natural sleep cycle and can alter hormonal and metabolic balance. Some studies have associated shift work with high blood pressure, increases in illnesses and injury, mental and emotional strain, and diseases such as diabetes and cancer.

Last year, a study published in the British Medical Journal found an increased risk of major vascular problems including heart attack and stroke, among shift workers. An international team from Canada and Norway examined 34 studies involving more than 2 million people, comparing shift workers to regular day-shift workers in similar jobs.

Shift work was associated with a 23 percent increased risk of heart attack; a 24 percent increased risk of coronary events such as cardiac-related death or coronary artery disease leading to hospital admission; and a 5 percent increased risk of stroke. People who worked the night shift had the highest increased risk — 41 percent — of coronary events.

Circadian rhythms also play a role in whether you might become an evening worker in the first place. Penn State University researchers found that people’s internal body clocks determine their “morningness” or “eveningness,” influencing students’ choices of college majors.

UMKC has several other researchers with interests in circadian rhythms. Jennifer Lundgren, associate professor and chair of the Department of Psychology, examines how circadian dysfunction can lead to excessive night-eating and obesity. Bi Botti Yuan of the School of Pharmacy has an interest in chronopharmaceutics, the science and technology for circadian rhythm-guided therapies and prevention of diseases.


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