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 Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)

nachricht Self-assembled nanostructures hit their target
23.09.2016 | King Abdullah University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Chains of nanogold – forged with atomic precision

23.09.2016 | Life Sciences

New leukemia treatment offers hope

23.09.2016 | Health and Medicine

Self-assembled nanostructures hit their target

23.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>