Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Insight into how the body tells time

25.06.2002


You may feel different at the dreary hour of 4 a.m. than you do mid-afternoon at 4 p.m. Now, researchers might understand why. A study from Washington University School of Medicine in St. Louis helps explain how genes dictate our biological clock.



Nearly all living things have a natural rhythm that influences their behavior and physiology. This rhythm typically is "circadian", following a near 24-hour cycle. Driven by an internal clock, a creature’s natural rhythm is synchronized to the outside world by external cues, like the sun. So far, the products of eight different genes have been discovered to be essential to the operations of this clock. Scientists believe that these genes, in turn, somehow influence the expression of other genes throughout the body in order to control the timing of behaviors like sleep and wakefulness.

Researchers from three laboratories at the School of Medicine, in collaboration with a team at Affymetrix, have identified 22 genes that appear to be rhythmically regulated by the internal clock of the Drosophila fly and found hundreds more genes that are regulated by both light and the internal clock. The study appears in the June 24 issue of the Proceedings of the National Academy of Sciences.


"Understanding how our internal environment responds to our innate biological clock could help us develop better ways of adjusting to challenging circumstances, like unusual work shifts or jet lag following a long journey," says lead investigator Paul H. Taghert, Ph.D., professor of anatomy and neurobiology.

The fruit fly Drosophila melanogaster is one of the most commonly studied organisms, particularly in the pursuit of understanding biological clocks. In the past, researchers only could estimate the number of genes affected by the eight clock genes. But now that the fly’s genome has been fully sequenced, scientists can scrutinize nearly all of the animal’s 14,000 genes.

The Washington University team capitalized on the genome database now available. Using a relatively new technology called DNA microarrays – comprehensive lists of all the active genes in a tissue sample – they measured the expression levels of nearly 14,000 genes at various time-points in the heads of normal flies and in flies missing one of the clock genes, called period.

All flies were exposed to light for 12 hours, followed by dark for 12 hours. The cycle continued for a total of 96 hours. Genetic analyses were performed on half of the flies at six different time-points on the fifth day.

The remaining flies were transferred into complete darkness for 48 hours. On the third day of darkness, the team again analyzed gene expression at each of six time-points. By exposing flies to constant darkness, the team hoped to detect genetic changes that are regulated by the internal circadian timekeeping system, rather than by external cues.

Overall, the researchers obtained over 70 readings for each of the nearly 14,000 genes, generating about a million individual measurements.

Using sophisticated computer-based statistical analyses, the team determined that between 72 and 200 of the flies’ 14,000 genes showed significant rhythms of gene expression in normal flies living in a daily light-dark cycle. Of these 72 genes, 22 continued to fluctuate when flies were collected after three days of complete darkness. This implies that these 22 genes are driven by the internal, circadian clock, not by external cues such as light.

Mutant flies lacking the period gene also were placed into the same two experimental conditions – light and dark fluctuations compared with complete darkness. The flies exposed to alternating light and dark still showed 18 genes with persistent, rhythmic oscillations, demonstrating that light and dark can directly drive rhythmic gene expression.

The remaining 32 of the 72 oscillating genes only fluctuated rhythmically in animals that still had the period gene and who were exposed to light and dark conditions. The biologic functions of most of these oscillating genes are unknown.

One of the most surprising results of the study was the discovery of hundreds of genes whose levels did not fluctuate with time of day, but responded drastically to different lighting conditions or to the presence or absence of a circadian clock.

"The fly’s ability to regulate a large fraction of all its genes depending on a combination of day length and the circadian clock gives us an attractive model for understanding seasonal timekeeping," says co-author Russell N. Van Gelder, M.D., Ph.D., assistant professor of ophthalmology and visual sciences. "Defects in seasonal timekeeping are thought to be related to seasonal affective disorder (SAD), in which individuals experience recurrent depression during the short days of winter."

Three similar studies were published immediately preceding this paper, each estimating the number of genes controlled by the internal clock to be more than 100. Eighteen of the 22 genes identified in this study also were identified by one of the other three studies. However, the majority (84 percent) of the remaining genes identified by the other three groups were not included in any of the other lists.

"We feel that our analysis provides a minimal set of circadian genes about which we can feel fairly confident," says Taghert.

In an effort to optimize research initiatives, the School of Medicine team has posted all of their raw data on the Internet at http://circadian.wustl.edu.


Lin Y, Han M, Shimada B, Wang L, Gibler TM, Amarakone A, Awad TA, Stormo GD, Van Gelder RN, Taghert PH. Influence of the period-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in Drosophila melanogaster. Proceedings of the National Academy of Sciences, June 24, 2002.

Funding from the National Institutes of Health, the Medical Scientist Training Program, the Research to Prevent Blindness Career Development Award, the Becker/AUPO/RPB Clinician-Scientist Award and from the Human Frontier Science Program Organization supported this research.


Gila Z. Reckess | EurekAlert!

More articles from Life Sciences:

nachricht Bacteria as pacemaker for the intestine
22.11.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia 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: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Corporate coworking as a driver of innovation

22.11.2017 | Business and Finance

PPPL scientists deliver new high-resolution diagnostic to national laser facility

22.11.2017 | Physics and Astronomy

Quantum optics allows us to abandon expensive lasers in spectroscopy

22.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>