Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Development of a molecular timetable by analysis of circadian gene expression

16.08.2004


A look inside a wristwatch reveals that timekeeping is a complex affair, involving the coordination of mechanical parts providing the impulses and feedback needed to achieve precisely recurring movement. Biological clocks are equally complex, regulated by a network of genes and transcriptional factors that interact to stabilize the rhythms of numerous physiological systems. Unlike the wristwatch, however, there is no visible readout or display showing an individual’s body time, a lack which has stood as one of the major barriers to realizing the promise of chronotherapy, which seeks to deliver drug treatments at optimal body times.



A new study by Hiroki R. Ueda (Laboratory for Systems Biology, RIKEN Center for Developmental Biology; Kobe, Japan) and colleagues has provided proof of principle that just such a display of individual body time may one day possible. The report, published in the August 3 issue of the Proceedings of the National Academy of Sciences, describes the analysis of the expression of more than 100 time-indicating genes in the mouse. The results of this genome-wide study enabled the authors to develop a "molecular timetable" that provides an accurate representation of the animal’s body time based on the sampling of gene expression levels at a single point in time.

Many genes exhibit variable expression cycles roughly over the course of a 24-hour day, a phenomenon known as circadian rhythmicity. In their study, Ueda et al. first identified genes that are expressed in high amplitude circadian patterns. Such genes demonstrate cyclical expression irrespective of variations in exposure to light, maintaining their amplitude and periodicity even when the animals are kept in constant darkness. The team identified 168 genes fulfilling these criteria in samples from mouse liver, and calculated their peak expression times in terms of both external time and the animal’s subjective inner clock. They found that the genes could be organized into a kind of daily schedule by their times of peak expression – some were expressed most highly at daybreak, some at dusk, some at other time-points throughout the cycle of a single day.


By plotting the expression levels of the entire set of time-indicating genes against a 24-hour curve, Ueda and colleagues found that it is possible to determine body time with a high degree of accuracy. To test the robustness of this molecular time measurement system, they measured the expression levels of the 168 genes at the lights-out phase in animals kept in conditions of alternating 12-hour periods of light and dark. This phase is presumed to be a hotbed of circadian regulatory activity, as the mouse’s internal rhythm runs in cycles that are naturally shorter than 24 hours, and darkness serves as a stimulus for resetting the circadian clock (such stimuli are referred to as Zeitgeber mechanisms, from the German word meaning "time-giver"). Their analysis of expression levels at this critical Zeitgeber hour 12 produced estimated body times to an accuracy of about 1 hour in all animals studied, indicating that the molecular timetable provided is strongly resistant to environmental noise (in this case, variation in exposure to light).

They next tested the system in mice with a homozygous mutation in the gene Clock, whose loss of function is known to perturb the natural circadian rhythm. They found rhythm disruptions in the expression profiles of all of the Clock/Clock mice, suggesting that the molecular timetable approach may also have applications in the diagnosis of circadian rhythm disorders.

This new approach to the horology of the body has been validated in mice of varying genetic backgrounds and in principle can be applied to any organism exhibiting biological clock activity, a range that spans the living world from bacteria to plants to humans. And indeed a test of the method in wild type and Clock-mutant fruit flies gave similar results to those in the mouse studies.

The development by Ueda and colleagues of a universally-applicable, specific, sensitive and accurate method capable of both detecting individual body time and of diagnosing circadian disorders represents a major step toward the fulfillment of the longstanding dream of scientists and physicians: to put a readable face on the body’s clock. Its application in medical treatment may one day allow doctors to tailor drug administration to a patient’s body time, which promises to optimize efficacy and reduce adverse effects.

Doug Sipp | EurekAlert!
Further information:
http://www.riken.jp

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>