Featured Research

from universities, journals, and other organizations

Work With Power Grids Leads To Cell Biology Discovery

Date:
March 19, 2008
Source:
Northwestern University
Summary:
Gene therapy is a promising experimental technique for the prevention and treatment of disease. Now a research team reports that a counterintuitive approach also holds promise. The targeted removal of genes can restore cellular function in cells with genetic defects, such as mutations. The results have ramifications for medical research as well as for optimizing certain metabolic processes used in the production of biofuels, such as ethanol.

Gene therapy, in which a working gene is inserted into a cell to replace a faulty or absent gene, is a promising experimental technique for the prevention and treatment of disease.

Now a research team led by a Northwestern University physicist reports that a counterintuitive approach also holds promise. The targeted removal of genes -- the exact opposite of what a gene therapist would do -- can restore cellular function in cells with genetic defects, such as mutations.

Published online in the journal Molecular Systems Biology, the results have ramifications for medical research as well as for optimizing certain metabolic processes used in the production of biofuels, such as ethanol.

After gathering extensive experimental information on the metabolic networks of three different single-celled organisms, the researchers built a general quantitative model that can be used to control and restore biological function to cells impaired by a genetic defect or by other factors that compromise gene activity. Their network-based method does this by targeted deletion of genes, forcing the cell to either bypass the functions affected by the defective gene or to compensate for the lost function.

The research, led by Adilson E. Motter, assistant professor of physics and astronomy in Northwestern's Weinberg College of Arts and Sciences and the paper's lead author, grew out of Motter's earlier work on the U.S. power grid -- another complex system that is very different from biological systems but also with many similarities.

After the 2003 Northeast blackout, where a sequence of failures in the power grid led to the largest outage in U.S. history, experts determined that the event could have been reduced or avoided by instigating small intentional blackouts in the system during the initial hours of instability.

"And the same could be valid in biology, where a defective gene may trigger a cascade of 'failures' along the cellular network," said Motter, whose interest and expertise lie in complex systems and understanding how the structure and dynamics of a high-dimensional system, such as an intracellular network or a power grid, relate to its function.

"Our recent research shows that what is true in power networks is also true in biological networks. Inflicting a small amount of damage can control what otherwise would be much more significant damage."

With the experimental information assembled, the researchers used their computer model to simulate the organism and its function. They started with a perfect cell and then, with a key gene deletion, damaged the cell so that it was unable to grow or had a significantly reduced growth rate.

Next, the researchers restored growth by deleting additional genes, which stimulated the cell to make a different choice and use different pathways. Interestingly, the cell's recovery was stronger when more genes were deleted. They could even restore growth to non-growing mutant cells; the researchers dubbed this the "Lazarus effect."

"Our research is based on optimizing the use of resources already available in the cell," said Motter. "We are exploring existing reactions and genes in the cell that the cell would not use or use to a lesser degree under normal conditions. This is different from traditional gene therapy, which is based on introducing new genes into the cell -- with its own advantages and problems because of that."

The team's use of predictive models is similar to how physicists use models, for example, to determine the position of the moon tomorrow at a specific time. Thanks to the recent wealth of available biological information, computational scientists now are beginning to develop quantitative models of biological systems that allow them to predict cellular behavior.

In one in silico experiment (via computer simulation) with E. coli, the researchers found that the deletion of one gene is lethal to the cell but when that same gene is removed along with other genes, it is not lethal. The gene, it turns out, is only essential in the presence of other genes. This touches the issue, says Motter, of whether organisms have an unconditional set of essential genes.

While Motter's team has not done actual laboratory experiments, they have used their computational results to re-interpret and explain specific recent experimental results. They have applied physics methods to solve a biological problem. Their method, for example, can identify the genes whose removal restores growth in gene-deficient mutants of E. coli and S. cerevisiae, a type of yeast.

"From a phylogenetic viewpoint, yeast is more similar to humans than E. coli," said Motter, a member of the Northwestern Institute on Complex Systems. "Of course, there is a distance between single-celled organisms and human cells, but our results should be seen as proof of principle. Many experimentalists are interested in our work, and part of this interest comes from its potential for disease treatment research. This work is a concrete application of complex networks to solve a real problem, and, as such, also requires substantial involvement of network theorists."

"Needless to say, this work is built on previous research and would not have been possible without the very significant contribution of my collaborators," said Motter.

In addition to Motter, other authors of the paper, titled "Predicting synthetic rescues in metabolic networks," are Natali Gulbahce, of Los Alamos National Laboratory and Dana Farber Cancer Institute; Eivind Almaas, of Lawrence Livermore National Laboratory; and Albert-Lαszlσ Barabαsi, of Northeastern University. (http://www.nature.com/msb/journal/v4/n1/full/msb20081.html)


Story Source:

The above story is based on materials provided by Northwestern University. Note: Materials may be edited for content and length.


Cite This Page:

Northwestern University. "Work With Power Grids Leads To Cell Biology Discovery." ScienceDaily. ScienceDaily, 19 March 2008. <www.sciencedaily.com/releases/2008/03/080317164339.htm>.
Northwestern University. (2008, March 19). Work With Power Grids Leads To Cell Biology Discovery. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2008/03/080317164339.htm
Northwestern University. "Work With Power Grids Leads To Cell Biology Discovery." ScienceDaily. www.sciencedaily.com/releases/2008/03/080317164339.htm (accessed August 28, 2014).

Share This




More Plants & Animals News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Australian Sheep Gets Long Overdue Haircut

Raw: Australian Sheep Gets Long Overdue Haircut

AP (Aug. 28, 2014) — Hoping to break the record for world's wooliest, Shaun the sheep came up 10 pounds shy with his fleece weighing over 50 pounds after being shorn for the first time in years. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Minds Blown: Scientists Develop Fish That Walk On Land

Minds Blown: Scientists Develop Fish That Walk On Land

Newsy (Aug. 28, 2014) — Canadian scientists looking into the very first land animals took a fish out of water and forced it to walk. Video provided by Newsy
Powered by NewsLook.com
Super Healthful Fruits and Vegetables: Which Are Best?

Super Healthful Fruits and Vegetables: Which Are Best?

Ivanhoe (Aug. 27, 2014) — We all know that it is important to eat our fruits and vegetables but do you know which ones are the best for you? Video provided by Ivanhoe
Powered by NewsLook.com
Bad Memories Turn Good In Weird Mouse Brain Study

Bad Memories Turn Good In Weird Mouse Brain Study

Newsy (Aug. 27, 2014) — MIT researchers were able to change whether bad memories in mice made them anxious by flicking an emotional switch in the brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins