Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New tool in the fight against tuberculosis

08.10.2010
Algorithm that integrates genomic and metabolic data enables cell-scale simulations and ultimately, biological strain design

Researchers at the Institute for Genomic Biology at the University of Illinois have developed a way to harness the prodigious quantities of both genomic and metabolic data being generated with high-throughput genomics and other techniques.

They have developed an algorithm that automatically integrates both data sets. The model, called probabilistic regulation of metabolism (PROM), enables researchers to perturb a given regulatory gene or metabolic process and see how that affects the entire network.

"PROM provides a platform for studying the behavior of networks in a wide range of different conditions," says principal investigator Nathan Price, an associate professor of chemical and biomolecular engineering at Illinois.

Using this model the researchers have created the first genome-scale, regulatory-metabolic network of Mycobacterium tuberculosis. Their results were published online by PNAS on September 27.

Using E. Coli as a benchmark, Price and graduate student Sriram Chandrasekaran showed that PROM was more accurate and comprehensive than the previous model for E. Coli, which had been done by hand and published in 2004.

After using E. Coli as a proof of principle, they targeted tuberculosis, a bacterium that has not been as thoroughly studied as E. Coli. Price and Chandrasekaran had less than half the amount of data then they had for E. Coli and were still able to create a model that predicted knockout phenotypes 95 percent of the time, says Price.

Price and Chandrasekaran built the algorithm using microarray data, transcription-factor interactions that regulate metabolic reactions, and knock-out phenotypes. The method is both accurate and fast. PROM may prove particularly helpful to tuberculosis researchers because, although when tuberculosis is growing it can be killed, the real challenge is to target the bacterium during its dormant or quiescent stage. PROM may enable researchers to identify and target the pathways keeping the cells alive during dormancy.

PROM also represents a major advance because it successfully integrates the statistically derived transcriptional regulatory network with a biochemically derived metabolic network.

"That is the new part," says Price. "People have created regulatory models and metabolic models. But there has been nothing before that could combine them in this automated fashion. It is difficult to get these two to talk to each other in the right way."

Price and Chandrasekaran created an algorithm that makes use of probability. Earlier models used a Boolean or a binary approach, in which a gene is either on or off. PROM can account for a gene or enzyme that can also be part way on or part way off, so it acts more like a rheostat than a toggle switch.

"People were stuck here for a long time. That's why PROM is such a nice method. It's sort of Boolean but it's probabilistic Boolean. It does allow us to have a continuous variation," says Price.

"These models can guide genome-scale synthetic biology," he adds. "And understanding how the networks are put together lays the foundation for us to design genomes that encode for networks that behave in the way we want them to, such as engineering microbes to convert environmental toxins into biofuels, for example."

Melissa Edwards | EurekAlert!
Further information:
http://www.illinois.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

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

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>