Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Two new studies on circadian rhythms

18.05.2009
Biological Timekeeper Studies Reveal New Temperature Regulator and Track Clock Protein across a Day

Dartmouth 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 clock-associated 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.

Co-authors with Dunlap, Loros, and Gerber, an assistant professor of genetics, are Christopher L. Baker,1 and Arminja N. Kettenbach.

The work was supported by National Institutes of Health grants from the National Institute of General Medical General Medical Sciences.

Sue Knapp | EurekAlert!
Further information:
http://www.dartmouth.edu

More articles from Studies and Analyses:

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>