SBS professor contributes to research leading to 2017 Nobel Prize in medicine

 

Three American scientists share the 2017 Nobel Prize in physiology or medicine for their discoveries on the molecular mechanisms that control circadian rhythms.

The Nobel committee awarded the prize to Jeffrey C. Hall, 72, retired from Brandeis University in Waltham, Mass.; Michael Rosbash, 73, Brandeis University; and Michael W. Young, 68, Rockefeller University in New York.

Dr. Jeffrey Price, associate professor at the School of Biological Sciences, is the co-author of two of the seven key publications leading up to this year’s award.

Price investigates the molecular and cellular mechanisms of circadian rhythms, which have periods of about 24 hours and are found in both unicellular and multicellular organisms. For example, human sleep-and-wake behavior is a circadian rhythm.

“If you were constructing a mechanical clock, you would want to have a set of instructions,” Price said. “We are working to understand biological clock principles.”

 NoblePrize.org

Using fruit flies in their experiments, this year’s laureates of the Nobel Prize discovered “the mechanism governing the self-sustaining clockwork inside the cell.” By adapting to different phases of the day, our inner clock regulates our behavior, sleep, hormone levels and metabolism.

Research on the circadian clock has many practical applications. It contributes to better understanding of the human biological clock, which, in turn, translates into research that helps people who work night shifts and are prone to suffer psychological problems.

“The biological clock is a powerful force,” Price said. “Our research may be applicable also, for example, to patients undergoing chemotherapy. Those experienced with chemotherapy have noticed that drugs have more effect during certain times of day.”

Price is the primary author on a 1998 paper describing DBT and published in Cell. The paper mentions Price’s and Young’s analysis of DBT—the protein kinase that is still the focus of Price’s current research. Working together for six years, 1989-1995, at Rockefeller University, they demonstrated that it phosphorylates PER and causes its degradation during the day. This leads to a delay in PER’s repression of its own transcription, thereby leading to elevated levels of per mRNA during the day and declining levels at night—the oscillations of per mRNA and proteins that underlie the circadian mechanism.

Price is second author on another cited paper, published in Science, that described the timeless protein (TIM), which interacts with PER to regulate PER’s accumulation and nuclear transport. PER is destabilized during the day because TIM is degraded in response to light, and then PER is phosphorylated by DBT and degraded.

“We were lucky that the fly clock works in much the same way as the human one!” Price said.

(bl)