Navigation Links
Work with power grids leads to cell biology discovery
Date:3/17/2008

EVANSTON, Ill. --- 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 Northwesterns Weinberg College of Arts and Sciences and the papers lead author, grew out of Motters 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 cells 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 teams 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 Motters 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.


'/>"/>

Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
Source:Eurekalert

Related biology news :

1. New twist on lifes power source
2. U of I researcher develops power-packed soy breakfast cereal
3. Genetic tags reveal secrets of memories staying power in mice
4. Powerful yet reliable proteomics techniques are the focus of a new methods book
5. Gene discovery made easier with powerful new networking technique
6. Department of Energy putting power in the hands of consumers through technology
7. There is powerful evidence of evolution in human DNA
8. Blood pressure drug telmisartan shows powerful activity against stroke
9. Wind power explored off Californias coast
10. Smarter energy storage for solar and wind power
11. The power of multiples: Connecting wind farms can make a more reliable - and cheaper - power source
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/5/2017)... 2017  The Allen Institute for Cell Science today ... one-of-a-kind portal and dynamic digital window into the human ... first application of deep learning to create predictive models ... and a growing suite of powerful tools. The Allen ... future publicly available resources created and shared by the ...
(Date:3/30/2017)... , March 30, 2017  On April 6-7, ... Hack the Genome hackathon at Microsoft,s headquarters ... two-day competition will focus on developing health and wellness ... Hack the Genome is the first ... tremendous. The world,s largest companies in the genomics, tech ...
(Date:3/27/2017)... , March 27, 2017  Catholic Health ... and Management Systems Society (HIMSS) Analytics for achieving ... Adoption Model sm . In addition, CHS previously ... U.S. hospitals using an electronic medical record (EMR). ... its high level of EMR usage in an ...
Breaking Biology News(10 mins):
(Date:4/27/2017)... ... ... Mitotech S.A, a Luxembourg based clinical stage biotechnology company, announced positive results of ... devastating genetic disease that leads to a sudden and rapid loss of central vision. ... 11778, 14484 and 3460 mutations and having experienced the onset of symptoms more than ...
(Date:4/27/2017)... ... April 27, 2017 , ... ... rebrand and a name change to Fluence Analytics. , Fluence Analytics ... of polymer and biopharmaceutical manufacturing processes and R&D applications. The company’s patented ...
(Date:4/26/2017)... ... April 26, 2017 , ... Looking ... team-building and cooking events company, offers one-of-a-kind gifts, ranging from gourmet cooking experiences ... California cuisine, and guests leave inspired with new cooking tips and techniques, thanks ...
(Date:4/26/2017)... ... April 26, 2017 , ... NextSteps 2017, NetDimensions’ annual global ... this May on the following dates: , ?    London, UK from May 10-11, ... Learning and Performance Institute will be the opening keynote speaker at the ...
Breaking Biology Technology: