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!
New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)
Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News