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 Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

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 pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>