Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify new drug target for treating jet lag and shift work disorders

02.09.2013
University of Notre Dame researchers, as part of a collaborative effort, have identified a protein that potentially could be a target for drugs that that would help people recover faster from jet lag and better adjust their circadian rhythms during rotational shift work.

The study appears in the Aug. 29th issue of the journal Cell. It can be found at: http://www.sciencedirect.com/science/article/pii/S0092867413009616

An internal circadian body clock helps virtually all creatures synchronize their bodily functions to the 24-hour cycle of light and dark in a day. However, travel to a different time zone, or shift work, disrupts the body's clock. Furthermore, it can take up to a day for the body to adjust to each hour that the clock is shifted, resulting in several days of fatigue, indigestion, poorer cognitive performance and sleep disturbance.

Giles Duffield, associate professor of biological sciences at Notre Dame and a member of the University's Eck Institute for Global Health, and Kevin Flanagan, a University alumnus and now a doctoral student at Washington University in St. Louis, characterized the protein SIK1, revealing that it plays a pivotal role in preventing the body from adjusting too quickly to changes in the environment.

Duffield and Flanagan, along with researchers from University of Oxford and F. Hoffman La Roche, and led by senior research scientist Stuart Peirson at the Nuffield Department of Clinical Neurosciences, identified roughly 100 genes that the body switches on in response to light, initiating a series of events that help to retune the body clock. They identified one gene and its corresponding protein product, called SIK1, that limits the body clock's ability to adjust to changes in the daily patterns of light and dark. In one particular experiment, when the researchers blocked the activity of SIK1 in laboratory mice, the mice adjusted faster to changes in the light-dark cycle that mimic a time zone change. The study proposes that the light-stimulated production of SIK1 in turn switches off the molecular pathway that feeds into the clock mechanism, thereby halting the shifting response of the biological clock.

"Our key contribution to the project was to manipulate the SIK1 protein pharmacologically, and we revealed that such blockage of the protein's activity in combination with exposure to a natural clock resetting agent, such as light, enhanced the clock shifting response," Duffield said. "For example, a one hour shift of the clock became two hours. We also showed this effect in both peripheral tissues as well as in the clock in the brain.

"It would appear that SIK1 plays a common role in our circadian clocks found throughout our body, and working as a hand-brake on our ability to shift our biorhythms and adjust to new time zones, whether these are real or artificial, such as those produced during shift work schedules."

In addition to the inconvenience of jet lag, disruptions in the circadian system, such as produced during shift work, have been linked to many diseases including diabetes, heart disease and cancer. Disturbances of the circadian clock have even been linked to mental disorders, such as schizophrenia, bipolar disease and seasonal affective disorder, also known as winter depression. It is important to note that approximately 16 percent of the U.S. and European workforces undertake some form of shift work.

"Having such a hand-break on the circadian clock systems makes sense so as to prevent excessive responses to environmental change, and that it is only in our modern 24-hour society, with Thomas Edison's light bulbs, Nikola Tesla's electricity, and jet airplanes, that we begin to realize our biological limitations," Duffield said.

The researchers' identification of the role SIK1 plays in the body clock offers a tractable target for drugs that could help us adjust faster to changes in time zone and help ameliorate the effects of rotational shift work.

"The fact that it is a kinase enzyme makes it an attractive target for the design of novel therapeutics," Duffield added.

Flanagan worked on the project as an undergraduate student, writing an honor thesis on his research data and presented his work at the Society for Research on Biological Rhythms meeting in 2012.

"Being involved in this project as an undergraduate student and presenting my data at an international conference really crystalized my interest in scientific research as a career," Flanagan said.

The Wellcome Trust, F. Hoffman La Roche and the National Institute of General Medical Sciences funded the research. Flanagan's participation was funded by a National Science Foundation Research Experiences for Undergraduates (REU) grant.

Giles Duffield | EurekAlert!
Further information:
http://www.nd.edu

More articles from Life Sciences:

nachricht The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences

nachricht Transforming plant cells from generalists to specialists
07.12.2016 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>