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Duke Research News optimizing patient care.”

eral cardiology rather than the interven-

“It’s important to be looking at this, be-

tional subspecialty nor did it explain the

cause we as a profession are not having

differences in the workload. But the study

full access to our ‘talent pool’ of qualified

In addition to Drs. Douglas and Jagsi, study

authors suggest that the differences could

internal medicine residents,” Dr. Douglas

authors include: Cathie Biga; Athena Pop-

stem from enduring gender inequities pro-

said. “That becomes a business and health

pas; George P. Rodgers; Mary N. Walsh;

fessionally and differences in choices in

care issue, as we increasingly recognize the

Patrick J. White; Colleen McKendry; Joseph

work/life balance.

importance of diversity among providers to

Sasson; and Phillip J. Schulte.

Finding Solves Circadian “Mystery” A team of scientists

adapts to diverse conditions, such as tem-

The findings have several implications. The

from Duke-NUS Gradu-

perature and metabolic changes.

phosphoswitch gives researchers and scientists a potential drug target to influence

ate Medical School Singapore (Duke-NUS) and

The research team found that the stability

the behavior of the circadian clock. This

the University of Michi-

of PER2 is dependent on a process called

new target may make it possible to counter

gan at Ann Arbor have

phosphorylation, in which phosphates are

the effects of jet lag, shift work and perhaps

discovered a molecular

added at key sites to influence the function

seasonal affective disorder.

switch that regulates the body’s circadian

of PER2. Dr. Virshup and the team discov-

clock and allows it to keep time. This switch

ered that phosphorylation acts as a switch.

The study also provides a mathematical

could be a potential drug target to treat cir-

This “phosphoswitch” leads to two alterna-

model that accurately predicts the behavior

cadian rhythm disorders caused by jet lag,

tive fates for PER2: increased stability or in-

of the clock under different circumstances.

shift work or metabolic disorders.

creased degradation.

This model will be useful in determining

David Virshup, M.D.

when drugs should be administered to Normally, the circadian body clock (24-

The researchers report that this phospho-

modify circadian rhythms, so they are most

hour cycle) is synchronized with the ris-

switch is sensitive to changes in tempera-


ing and setting of the sun, ensuring that

ture and metabolic signals, and so it fine-

we sleep at night. One of the reasons this

tunes clock speed as needed. Usually, the

The next step for the team is to test their

is possible is because the body clock is

rate of a biochemical reaction increases as

predictions in an animal model. They plan

relatively insensitive to small changes in

the temperature rises, so in this case the

to explore more about how phosphatases,

temperature. This is important, because

speed of the body clock should increase

an enzyme found in the body, and other

otherwise the body clock could run too

if the temperature rises. However, the team

kinases may be important in regulating the

fast when it is hot or too slow when it is

showed that at higher temperatures, the

circadian clock. Their current hypothesis is

cold. A long-standing scientific mystery is

phosphoswitch ensures that degradation

that the interplay of these systems will regu-

how the human body clock compensates

of PER2 is slower, therefore maintaining the

late the sleep and wake cycle.

for changes in temperature and maintains

speed of the body clock. In addition to Dr. Virshup and Dr. Forger,

its speed. “This study sheds light on one of the biggest

study authors include first author Duke-

Over the past few decades, research has

mysteries of the circadian clock in the last

NUS research fellow Min Zhou and KAIST

advanced the understanding of the circa-

60 years and has helped to explain some

(Korean Advanced Institute of Science

dian clock. One of the proteins critical for

of the basic mechanisms that govern the

and Technology) mathematician assistant

determining the timing of the clock, as well

timing of the clock,” explained Dr. Virshup,

professor Jae Kyoung Kim. This research

as the timing of sleep, is Period2 (PER2).

director of the Cancer and Stem Cell Biol-

is supported by the Singapore Ministry of

ogy Programme at Duke-NUS and professor

Health’s National Medical Research Coun-

In the current study, published Oct. 1 in

of pediatrics at the Duke University School

cil under its Investigator Research Grant.

the journal Molecular Cell and led by David

of Medicine. “By using both biochemical

Virshup, M.D., from Duke-NUS and Daniel

analysis and mathematical modeling we

For more information, please visit www.

Forger, Ph.D., from Michigan, the findings

demonstrated how the core circadian clock

shed light on how PER2 regulates our cir-

keeps to a 24-hour cycle despite tempera-

cadian clock. It also clarifies how the clock

ture changes and metabolic changes.”

january 2016


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