Navigation Links
Researchers identify new drug target for treating jet lag and shift work disorders
Date:8/30/2013

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.


'/>"/>

Contact: Giles Duffield
Giles.E.Dufield.2@nd.edu
574-631-1834
University of Notre Dame
Source:Eurekalert

Related medicine news :

1. NIH awards $20 million over 5 years to train next generation of global health researchers
2. Researchers develop a new cell and animal model of inflammatory breast cancer
3. Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance
4. Researchers Find Gene Mutations That May Be a Key to Autism
5. Researchers find evidence of banned antibiotics in poultry products
6. NJ stroke researchers report advances in spatial neglect research at AAN Conference
7. Autism by the numbers: Yale researchers examine impact of new diagnostic criteria
8. Researchers Map Brain Regions Linked to Intelligence
9. Researchers ID Genes That May Determine Mental Illness
10. Researchers Develop Blood Test for Depression
11. University of Cincinnati researchers win $3.7M grant from US Department of Defense
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/20/2017)... ... 2017 , ... “The Angel”: a heartwarming and earnest tale of faith ... his children. “The Angel” is the creation of published author, Marjorie Lund-Fontaine, a former ... impassioned writer. , When asked of her new book, Marjorie says, “‘The Angel’ was ...
(Date:1/20/2017)... ... January 20, 2017 , ... “Journey to Christmas:” a beautiful and enchanting tale that teaches ... Kimberly Cordoves, a mother of three in Oklahoma City, and a devoted woman of faith. ... a book has been in the back of my mind for years, but actually doing ...
(Date:1/19/2017)... ... January 19, 2017 , ... Aerolib ... system for Clinical and Regulatory education for Physicians, Physician Advisors, Case managers, ... education methodology of Disease Specific Documentation Improvement. , The Aerolib Learning Management ...
(Date:1/19/2017)... ... 19, 2017 , ... LabRoots , the leading provider ... world, announces the launch of its newly redesigned website. The sleek new design ... and trending news, vital information on upcoming virtual events and webinars, all while ...
(Date:1/19/2017)... (PRWEB) , ... January 19, 2017 , ... ... technologies and development solutions for drugs, biologics and consumer health products, today announced ... Lipids,” with Gattefossé, the leader in innovative excipients and drug delivery solutions to ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... , Jan. 18, 2017  ViewRay, Inc. (Nasdaq: ... first and only clinical MRI-guided radiation therapy system, announced ... of approximately $26.1 million through a private placement ... Management led the financing and was joined by ... LLC and Kearny Venture Partners, and an additional ...
(Date:1/19/2017)... , Jan. 18, 2017 The drug ... billion by 2021 from USD 1,179.20 billion in 2016, ... Increasing prevalence of chronic diseases, increasing demand for ... factors driving the growth of this market. Whereas, self-administration ... generic drugs offer significant growth opportunities for players operating ...
(Date:1/18/2017)... 18, 2017  Aprima Medical Software, a leading ... management (PM) and revenue cycle management (RCM) solutions ... a former reseller Healthcare Data Solutions (HDS) of ... Aprima will assume full support for HDS,s customers, ... practices across 15 states. Financial terms were not ...
Breaking Medicine Technology: