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!
The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig
Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Physics and Astronomy
21.11.2017 | Life Sciences