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 The hidden structure of the periodic system
17.06.2019 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht Tiny probe that senses deep in the lung set to shed light on disease
17.06.2019 | University of Edinburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

Im Focus: Tube anemone has the largest animal mitochondrial genome ever sequenced

Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.

The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....

Im Focus: Tiny light box opens new doors into the nanoworld

Researchers at Chalmers University of Technology, Sweden, have discovered a completely new way of capturing, amplifying and linking light to matter at the nanolevel. Using a tiny box, built from stacked atomically thin material, they have succeeded in creating a type of feedback loop in which light and matter become one. The discovery, which was recently published in Nature Nanotechnology, opens up new possibilities in the world of nanophotonics.

Photonics is concerned with various means of using light. Fibre-optic communication is an example of photonics, as is the technology behind photodetectors and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Novel communications architecture for future ultra-high speed wireless networks

17.06.2019 | Information Technology

Climate Change in West Africa

17.06.2019 | Earth Sciences

Robotic fish to replace animal testing

17.06.2019 | Ecology, The Environment and Conservation

VideoLinks
Science & Research
Overview of more VideoLinks >>>