Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

’Timeless’ gene found to play key role as timekeeper in mammals

17.10.2003


In 1998, scientists found the mammalian version of a gene, known as timeless, which in flies is crucial for the biological clock. However, all but one of the research groups involved determined that timeless did not have such a role in mammals. Now that research group says timeless is indeed a key timekeeper in mammals.



In a new complex molecular study of rats, published in the Oct. 17 issue of Science, researchers at the University of Illinois at Urbana-Champaign blocked the functional ability of timeless, leaving the circadian clock in disarray.

The key difference between the previous studies and this new one was the identification of two timeless proteins -- one a full-length protein and the other a shorter, incomplete version.


"There has been a lot of dispute about the role of timeless, and timeless has been generally excluded in research done since 1998," said Martha U. Gillette, the head of the department of cell and structural biology at Illinois. In the initial studies, her lab had seen differences in timeless RNA expression. The other labs had not.

The research in Gillette’s lab, led by Jessica W. Barnes and Jeffrey A. Barnes, both doctoral students, and Shelley A. Tischkau, a professor of veterinary biosciences, continued with the goal to decipher the previously conflicting findings.

"This paper has substantial supportive data that provides definitive evidence that timeless needs to be back in the loop," Gillette said. Much of the supporting data, in fact, is presented online to complement the material appearing in the Science paper.

The "loop" is the 24-hour circadian rhythm in the brain and cells. It consists of an automatically regulated loop of transcription and translation of gene products important for many diverse physiological functions such as sleep, metabolism and reproduction.

The earlier findings had led to the conclusion that timeless was vital only to cellular development in mammals but not to the clock. "The other labs had targeted their reagents at the end of the gene where changes in only full-length timeless are difficult to isolate due to the over-abundance of the short isoform," Jessica Barnes said. "So their results were being confounded."

Working with the whole molecule, the interaction of timeless with the five other mammalian clock genes (three forms of mPER, mClk and bmal) became clear.

In normal and control-treated brain slices from the rats’ suprachiasmatic nucleus, the site of the circadian clock, normal activity occurred in the presence of timeless. When specially designed antisense molecules were added to block it, electrical rhythms were disrupted. "When you have really low levels of timeless, you also disrupt the other clock genes," Barnes said. "You get an uncoupling. The clock is very much in disarray."

Some clock genes send positive signals, triggering mRNA production. The Illinois team theorizes that timeless and another clock gene (mPER2) work in tandem as negative signals to shut down mRNA production during the 24-hour cycle. With timeless back in the mammalian equation, it means that the clock genes of Drosophila and mammals correspond and function similarly.

"This conservation of timeless is very important, that what is happening in Drosophila is holding true in the mammal," Gillette said. "Without timeless, you are missing a whole set of gears in an intricate mechanism."

Other contributors to the paper were postdoctoral researchers Jennifer W. Mitchell and Penny W. Burgoon, both in cell and structural biology, and Jason R. Hickok, a doctoral student in cell and structural biology.


The U.S. Department of Health and Human Services, the University of Illinois Scholars Program and the Illinois Governor’s Venture Technology Fund/Molecular & Endrocrine Pharmacology Program supported the research.

Jim Barlow | EurekAlert!
Further information:
http://www.uiuc.edu/

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>