Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Setting the cellular clock

Synthetic genetic circuits enable researchers to uncover the mechanisms by which cells set their internal clocks

Many organisms live out their lives on schedules established by internal clock mechanisms, generated by the combined action of multiple regulatory networks that interlock like gears in a watch. The resulting circadian rhythms establish one’s internal perception of day and night, as well as numerous time-points in between.

In 2005, a team led by Hiroki Ueda of the RIKEN Center for Developmental Biology in Kobe made significant progress in identifying the core components of the complex circadian circuitry1. They found several regulatory elements that specifically mark genes for activation or inhibition in the morning, daytime or night, as well as numerous genes that mediate regulation via these elements.

“Our team identified a natural transcriptional circuit for mammalian circadian clocks,” explain Maki Ukai-Tadenuma and Takeya Kasukawa, members of Ueda’s team. “However, no one has yet confirmed the mechanism that generates practically continuous phases from these three, discrete basic phases.”

However, the investigators had ideas about how such patterns might emerge, and were able to sketch a rough map of how the various time-specific regulatory loops may interact in vivo to produce a stable day–night cycle. To test their hypotheses, they constructed a series of synthetic circadian circuits within live cells based on their models, and examined the extent to which their activity replicated natural biological cycles2.

In fact, these experimental scenarios provided strong support for their regulatory models. One of the synthetic circuits consisted of a bioluminescent indicator gene under the regulation of a morning-specific activator and a nighttime-specific repressor, and the resulting pattern of indicator activity was a cyclic oscillation that very closely matches the natural expression pattern of daytime-specific genes.

They were similarly able to replicate night-cycle activity with a daytime-specific activator and morning-specific repressor, and were even able to generate novel ‘late night’ or ‘dusk’ output peaks by further tinkering with the timing of activation and repression. Most importantly, their experimental findings were all consistent with the predictions of their previously developed theoretical models. “Both our simulation model and the derived design principles successfully recapitulated the natural transcriptional circuit in the circadian clocks,” say the researchers.

Although their modeling system has proven effective, the researchers have yet to fully reconstruct all the phases of the mammalian circadian cycle. “In our study, morning transcriptional regulation is still a ‘missing link’,” they point out. The team’s focus now is on successfully identifying the regulatory processes required to restore these final time-points to their reconstructed cellular clock.


1. Ueda, H.R., Hayashi, S., Chen, W., Sano, M., Machida, M., Shigeyoshi, Y., Iino, M. & Hashimoto, S. System-level identification of transcriptional circuits underlying mammalian circadian clocks. Nature Genetics 37, 187–192 (2005).

2. Ukai-Tadenuma, M., Kasukawa, T. & Ueda, H.R. Proof-by-synthesis of the transcriptional logic of mammalian circadian clocks. Nature Cell Biology 10, 1154–1163 (2008).

The corresponding author for this highlight is based at the RIKEN Laboratory for Systems Biology

Saeko Okada | ResearchSEA
Further information:

More articles from Life Sciences:

nachricht ‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>