Navigation Links
Two new studies on circadian rhythms
Date:5/15/2009

Hanover, NHDartmouth Medical School geneticists have made new inroads into understanding the regulatory circuitry of the biological clock that synchronizes the ebb and flow of daily activities, according to two studies published May 15.

Research on the relationship between clocks and temperature, reported in Cell, offers insight into a longstanding puzzle of temperature compensation: why the 24-hour circadian rhythm does not change with temperature when metabolism is so affected.

A related study, in Molecular Cell, tracks a clock protein in action, mapping hundreds of highly choreographed modifications and interactions to provide the first complete view of regulation across a day.

The new work adds clarity to the molecular underpinnings of circadian clocks, the finely tuned cellular timekeepers that drive most organisms. Circadian systems are biological oscillators that orchestrate activities through an elaborate network of interactive proteins and feedback loops. All clocks rely on transfer of phosphate groups, called phosphorylation, to clock proteins for setting the 24-hour cycle.

Both studies looked at phosphorylation of the frequency (FRQ) clock protein, a central feedback cog in the fungal clock system. They build on the research of team leaders, Drs. Jay Dunlap and Jennifer Loros, who have documented the workings of FRQ and most other components in the Neurospora clock.

"The Cell paper describes how the cell uses phosphorylation of a clock protein to keep the period length of the cycle close to the same across a range of temperatures. This phenomenon, called temperature compensation, is one of the few canonical properties of rhythms that still lack molecular description," said Dunlap.

"The one in Molecular Cell describes collaborative work with Dr. Scott Gerber in the Norris Cotton Cancer Center. We used mass spectrometry to follow the degree of phosphorylation of over 75 sites on the FRQ clock protein across the day. Most proteins have one or a few phosphorylations, so following these across time is a major technical achievement as well as being informative for the clock biology."

In Cell, the researchers suggest a new role for the clockassociated enzyme, casein kinase (CK)2 as a key control for temperature compensation. Pursuing two uncharacterized circadian protein mutants shown to affect compensation in an unusual way, the investigators identified different subunits of the same enzyme, CK2.

They developed new ways to manipulate the genome and showed, by controlling expression, that the level of CK2 dictates the form of compensation through the phosphorylation of the clock protein FRQ. The property is unique to CK2 and shared with none of the other similar enzymes implicated in clock function.

Coauthors in addition to Dunlap, professor of genetics and Loros, professor of biochemistry and of genetics, are Arun Mehra, Mi Shi, Christopher L. Baker, Hildur V. Colot.

The second study traced protein interactions throughout the cycles to demonstrate how phosphorylation controls circadian rhythm. Using a heavy isotope labeling method and quantitative mass spectrometry, the researchers pinpointed a near record number of modifications on FRQ and described how each appears and disappears over the day.

Moreover, their methods facilitated the identification of interacting proteins to track and correlate changes in the core circadian network. They determined the clusters and locations of known sites, and through mutational analysis identified novel functional domains to create a dynamic view of a clock protein in action.


'/>"/>

Contact: Sue Knapp
dms.communications@dartmouth.edu
603-650-1492
Dartmouth College
Source:Eurekalert

Related biology news :

1. New early detection studies of lung cancer in non-smokers launched today
2. Scripps studies offer new picture of Lake Tahoes earthquake potential
3. Analysis finds strong match between molecular, fossil data in evolutionary studies
4. Peregrines PS-targeting antibodies highlighted in AACR Annual Meeting studies
5. Free online toolkit provides standard measures for genome and population studies
6. GSA special paper presents new studies of Western US earth motion
7. West Nile virus studies show how star-shaped brain cells cope with infection
8. Alzheimers disease therapeutic prevents long-term damage from TBI in pre-clinical studies
9. Autism Speaks funds $5 million to studies on genetic and environmental risk factors for autism
10. New tool for genome-wide association studies
11. Execretion analysis aids primate social studies
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/6/2017)... , May 5, 2017 RAM ... announced a new breakthrough in biometric authentication based ... quantum mechanical properties to perform biometric authentication. These new ... semiconductor material created by Ram Group and its ... entertainment, transportation, supply chains and security. Ram Group ...
(Date:4/13/2017)... April 13, 2017 UBM,s Advanced Design and ... will feature emerging and evolving technology through its 3D ... will run alongside the expo portion of the event ... and demonstrations focused on trending topics within 3D printing ... and manufacturing event will take place June 13-15, 2017 at ...
(Date:4/11/2017)... MELBOURNE, Florida , April 11, 2017 ... "Company"), a security technology company, announces the appointment of independent ... John Bendheim to its Board of Directors, furthering the ... ... behalf of NXT-ID, we look forward to their guidance and ...
Breaking Biology News(10 mins):
(Date:9/19/2017)... ... 19, 2017 , ... Band-LOK, LLC, an orthopedic medical device ... new patents have been allowed by the USPTO on the proprietary Tether Clamp ... to explore additional clinically-relevant designs for both the implants and the instrumentation. ...
(Date:9/17/2017)... ... September 17, 2017 , ... ... Korean Ministry of Food and Drug Safety (KMFDS) for an Investigational New Drug ... Middle East Respiratory Syndrome coronavirus (MERS-CoV). The study in Korea represents the second ...
(Date:9/14/2017)... ... September 14, 2017 , ... Boston Strategic Partners, ... with Health Economics and Outcomes Research (HEOR) and ‘big data’ to provide in-depth ... US healthcare spending exceeded $3.0 trillion with nearly 1/3 spent on hospitalizations. BSP ...
(Date:9/13/2017)... , ... September 13, 2017 , ... ... the life sciences industry to improve patient outcomes and quality of life for ... impurities, has been named a US expert to the International Standards Organization/Technical ...
Breaking Biology Technology: