Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCSD bioengineers develop first genome-scale computational model of gene regulation

06.05.2004


Results published in May 6 Issue of Nature



It has taken more than 50 years to accumulate the current body of knowledge on Escherichia coli, a bacterium which is one of the best studied organisms in biology. Now, bioengineers at the University of California San Diego have integrated this knowledge into the first genome-scale model of the gene regulatory system in E. coli. The computational model helps to define the rules governing cell function and quickly enabled an exponential increase in the understanding of the regulatory system in E. coli. Their work, which is published in the May 6, 2004 issue of Nature, represents a new way to systematically drive biological discovery.

"This research is evidence of how much more quickly biological discovery is going to progress now, given that we have high-throughput experimental tools for gathering large volumes of data, and the use of these tools can be guided by computer models," said Bernhard Palsson, professor of bioengineering at the UCSD Jacobs School of Engineering. Palsson co-authored the study with his UCSD bioengineering student Markus Covert, who is now a post-doctoral researcher at the California Institute of Technology.


"We have demonstrated that we can reverse-engineer a cellular regulatory system at the genome scale, and then use that model to systematically gain new knowledge about how the cell functions," said Palsson.

In 2000, Palsson completed an in silico (computational) model of E. coli metabolism that is now being used by scientists worldwide to design and interpret laboratory experiments as well as engineer strains for industrial purposes. In this more recent work, Covert modeled the regulatory network in E. coli representing how the cell responds to environmental cues and expresses genes involved in cellular metabolism. He scoured the scientific literature to reconstruct an E. coli model incorporating all known data about regulatory network components, their functions and their actions.

The UCSD model now includes a network for 1,010 genes, including 104 regulatory genes, whose products together with other molecules regulate the expression of 479 of the 906 genes known to be involved in metabolism.

The team conducted a series of experiments focused on E. coli’s response to oxygen deprivation. They made predictions of cellular behavior through simulations with the in silico model. These predictions guided high-throughput data-gathering experiments using gene chip technology. In the laboratory, the team created strains of E. coli in which genes involved in oxygen regulation were deleted, and then subjected the strains to experiments both with and without oxygen. When the predicted outcomes did not match the experimental outcomes, the experimental data was used to update the in silico model.

Through this process, the team uncovered surprising new details about how E. coli responds to oxygen deprivation.

"We went into the experiments thinking that oxygen regulation is fairly well understood. But in one fell swoop, we identified 115 previously unknown regulatory mechanisms," said Covert. "For example, one interesting finding was that in several cases when a protein that transcribes a gene is active, the expression level of that gene is actually reduced. We also identified new regulatory interactions for genes that no one previously had described, basically opening up a whole new research frontier in terms of characterizing regulatory networks in E. coli."

Another observation by the team was that E. coli’s regulatory network is much more complex than might be expected for such a relatively simple single-cell microbe. And that, Covert says, means that lessons learned through the E. coli modeling process will help scientists model much more advanced organisms such as mice and even humans.

UCSD has filed a patent on the model and is negotiating a license agreement. Palsson’s group at UCSD will continue to develop the E. coli model, and is also beginning to model the regulatory network in yeast, a single-cell organism more closely related to human cells. Meanwhile Covert at Caltech is focusing on signaling transduction pathways in the mouse.

In addition to Palsson and Covert, the other researchers involved in the study include Eric M. Knight, Jennifer L. Reed, and Markus J. Herrgard.


Funding was provided through the National Institutes of Health.

Denine Hagen | EurekAlert!
Further information:
http://gcrg.ucsd.edu/
http://www.jacobsschool.ucsd.edu

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>