The researchers in the UC College of Medicine Department of Molecular and Cellular Physiology, led by Christian Hong, PhD, published their findings Monday, Jan. 13, online ahead of print in PNAS (Proceedings of the National Academy of Sciences).
"Our work has large implications for the general understanding of the connection between the cell cycle and the circadian clock,” says Hong, an assistant professor in the molecular and cellular physiology department who collaborated with an international team of researchers on the project.
Funding for Hong’s research was provided by a four-year, $3.7 million grant from the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S. Department of Defense. He also received startup funds from UC’s molecular and cellular physiology department.
The circadian rhythm, often referred to as the biological clock, is a cycle of biological activity based on a 24-hour period and generated by an internal clock synchronized to light-dark cycles and other external cues.
"Everything has a schedule, and we are interested in understanding these schedules at a molecular level,” Hong says. "We also wanted to know the components that connect two different oscillators (the circadian clock and cell division, or mitosis).”
Using the filamentous (thread-like) fungi Neurospora crassa, the researchers investigated the coupling between the cell cycle and the circadian clock using mathematical modeling and experimentally validated model-driven predictions. They demonstrated a mechanism that is conserved (constant) in Neurospora as in mammals, which results in circadian clock-gated mitotic cycles.
"The cell divisions happened during a certain time of day,” Hong says, "and they were molecularly regulated by the mechanisms of circadian rhythms.”
The researchers showed that a conserved coupling between the circadian clock and the cell cycle exists via serine/threonine protein kinase-29 (STK-29), the Neurospora homolog (possessing similar DNA sequence) of mammalian WEE1 kinase.
Additionally, the researchers conducted phase-shift experiments in which they transferred Neurospora to constant darkness, then administered a 90-minute pulse of white fluorescent light at indicated time points in order to induce phase-shift.
"We were able to show that when we phase-shift the circadian clock, we also observe phase-shifting of the cell cycle components,” Hong says.
By building on experimentally validated mathematical models from Neurospora, researchers will be able to make predictions in other Neurospora strains and mammalian cells.
As Hong puts it, "This discovery will serve as a stepping stone for further investigations to uncover conserved principles of coupled mechanisms between the cell cycle and circadian rhythms.”
Keith Herrell | EurekAlert!
Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
20.11.2018 | Life Sciences
20.11.2018 | Life Sciences
20.11.2018 | Physics and Astronomy