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!
Polymers Based on Boron?
18.01.2018 | Julius-Maximilians-Universität Würzburg
Bioengineered soft microfibers improve T-cell production
18.01.2018 | Columbia University School of Engineering and Applied Science
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
18.01.2018 | Life Sciences
18.01.2018 | Life Sciences
18.01.2018 | Earth Sciences