Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cellular pathway includes a ’clock’ that steers gene activity

08.11.2002


Understanding the timed messages within cells could lead to new medical treatments



Researchers from The Johns Hopkins University and other institutions have discovered a biochemical "clock" that appears to play a crucial role in the way information is sent from the surface of a cell to its nucleus. These messages can cause the cell to thrive or commit suicide, and manipulating them could lead to new treatments for cancer and other diseases, the researchers say.

The findings, based on lab experiments conducted at Cal Tech and computer models developed at Johns Hopkins, are reported in the Nov. 8 issue of the journal "Science."


Scientists have known that living cells send messages from their surfaces to their nuclei by setting off a chain of chemical reactions that pass the information along like signals traveling over a telephone wire. Such reaction chains are called signaling pathways. But while studying one such reaction chain called the NF-kappaB pathway within mouse cells, the university researchers learned that the signal transmission process is even more complicated.

"We found that if the pathway was activated for a short time, a single pulse of activity was delivered to the nucleus, like a single tick of a clock, activating a set of genes," said Andre Levchenko, assistant professor in the Department of Biomedical Engineering at Johns Hopkins. "But longer activation could produce more pulses and induce a larger gene set. We believe that the timing between pulses is critical. If too much or too little time elapsed, the genetic machinery would not respond properly."

Levchenko, a lead author on the "Science" paper, and his colleagues concluded that the signaling pathway inside a cell was serving as much more than a simple wire. "It was not just carrying the information, it was processing it," he said. "The pathway was operating like a clock with a pendulum, delivering the signal at particular intervals of time in a way that could resonate with the behavior of the genes in the nucleus."

When information moves through a cell pathway to genes in the nucleus, it prompts the genes to send out their own instructions, directing the cell to assemble proteins to carry out various tasks. By developing a better understanding of the way information travels along a pathway, Levchenko said, researchers may be able to create drugs that disrupt or change this line of communication, and in turn affect overall functioning within the cell. For example, a drug designed to shut down the NF-kappaB pathway might cause a cancer cell to commit suicide through a biological process called apoptosis. "We know that cancer cells use this pathway," he said. "If we can find a smart way to cut this ’wire,’ it will be much easier to kill the cancer cells."

Levchenko and his colleagues made their discovery by first developing a computer model showing how they believed the pathway operates. Then they verified their results by studying live cells in the lab. Finally, they used the validated model to guide further experiments. Although mouse cells called fibroblasts were used, Levchenko said the findings should also hold true for human fibroblasts and other cell types.

Because the computer model has been validated, it could be used to speed up the development of pharmaceuticals that might affect the cell pathway, said Levchenko, who is a part of a computational biology research team based at the Whitaker Biomedical Engineering Institute at Johns Hopkins. He said drug developers could use the computer model to quickly test how various compounds may affect the cell behavior before launching more time-consuming lab tests with live cells. "This has given us a very good tool to predict things that may happen when the pathway properties are altered, reducing the need to engage in exhaustive animal tests," Levchenko said.


The other lead author of the Science paper was Alexander Hoffman, who engaged in the research as a postdoctoral scholar at Cal Tech and now is an assistant professor of biology at the University of California, San Diego. The co-authors were Martin L. Scott, who conducted research at MIT and who now is employed by Biogen Inc.; and David Baltimore, president of Cal Tech.

Color Image of Andre Levchenko available; Contact Phil Sneiderman Related Links:

Andre Levchenko’s Web page: http://www.bme.jhu.edu/~alev
Johns Hopkins Department of Biomedical Engineering: http://www.bme.jhu.edu

THE JOHNS HOPKINS UNIVERSITY
OFFICE OF NEWS AND INFORMATION
3003 N. Charles Street, Suite 100
Baltimore, Maryland 21218-3843
Phone: (410) 516-7160 / Fax (410) 516-5251


Phil Sneiderman | EurekAlert!
Further information:
http://www.jhu.edu/

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

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

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>