To: Owl_Eagle
10 posted on 11/14/2002 8:28 AM PST by Stand Watch Listen
Posted on 11/14/2002 9:19:45 PM PST by Nebullis
For more than a decade, researchers have been trying to create accurate computer models of Escherichia coli (E. coli), a bacterium that makes headlines for its varied roles in food poisoning, drug manufacture and biological research.
By combining laboratory data with recently completed genetic databases, researchers can craft digital colonies of organisms that mimic, and even predict, some behaviors of living cells to an accuracy of about 75 percent.
Now, NSF-supported researchers at the University of California at San Diego have created a computer model that accurately predicts how E. coli metabolic systems adapt and evolve when the bacteria are placed under environmental constraints. Bernhard Palsson, Rafael Ibarra (now at GenVault Corporation in Carlsbad, California) and Jeremy Edwards (now at the University of Delaware at Newark) report their findings in the November 14 issue of Nature.
"Ours is the only existing genome-scale model of E. coli," says Palsson. In addition, while many approaches to genetics experiments "knock out" individual genes and track the results, the new model takes a whole-system approach. Changing one aspect of a genetic code could be irrelevant if an organism adapts and evolves, says Palsson. The constraints-based models allow the E. coli to evolve more naturally along several possible paths.
Scientists may use the approach to design new bacterial strains on the computer by controlling environmental parameters and predicting how microorganisms adapt over time. Then, by recreating the environment in a laboratory, researchers may be able to coax living bacteria into evolving into the new strain.
The resulting strains may be more efficient at producing insulin or cancer-fighting drugs than existing bacterial colonies engineered by researchers using standard techniques.
"Now we have a better tool to predict how bacteria evolve and adapt to changes," says National Science Foundation program director Fred Heineken. "As a result, this constraints-based approach could lead to better custom-built organisms," he says.
The researchers based their digital bacteria on earlier laboratory studies and E. coli genome sequences, detailed genetic codes that have been augmented with experimental information about the function of every gene.
Such digital models are known as "in silico" experiments.
In the first days of testing on living organisms, the bacteria did not adapt into the strain predicted by the simulation. Yet, with more time (40 days, or 500-1000 generations), the E. coli growing in the laboratory flasks adapted and evolved into a strain like the one the in silico model predicted.
"The novelty of the constraints-based approach is that it accounts for changes in cellular properties over time," says Palsson. "Fortunately," he adds, "the other advantage is that it actually works surprisingly often."
For many years, drug manufacturers have manipulated the genetic code in E. coli strains, creating species that can produce important substances, such as the hormone insulin for use by people with diabetes or the experimental cancer drug angiostatin.
Using the new constraints-based techniques Palsson and his colleagues developed, drug manufacturers and bioprocessing companies could use computers to determine the genetic code that could yield the most efficient and productive versions of E. coli, and then use adaptive evolution to create bacterial strains that have the desired properties.
Says Palsson, "This development potentially opens up a revolutionary new direction in the design of new production strains." In addition, says Palsson, "now that we have gained a greater understanding of this process in E. coli, developing similar simulations of other organisms should take less time."
The left turning proteins found in E. Carville are unnatural.
10 posted on 11/14/2002 8:28 AM PST by Stand Watch Listen
Annotated genome sequences can be used to reconstruct whole-cell metabolic networks. These metabolic networks can be modelled and analysed (computed) to study complex biological functions. In particular, constraints-based in silico models have been used to calculate optimal growth rates on common carbon substrates, and the results were found to be consistent with experimental data under many but not all conditions. Optimal biological functions are acquired through an evolutionary process. Thus, incorrect predictions of in silico models based on optimal performance criteria may be due to incomplete adaptive evolution under the conditions examined. Escherichia coli K-12 MG1655 grows sub-optimally on glycerol as the sole carbon source. Here we show that when placed under growth selection pressure, the growth rate of E. coli on glycerol reproducibly evolved over 40 days, or about 700 generations, from a sub-optimal value to the optimal growth rate predicted from a whole-cell in silico model. These results open the possibility of using adaptive evolution of entire metabolic networks to realize metabolic states that have been determined a priori based on in silico analysis.
Better than average teaser!
I want to see the program evidence.
Are they saying that they can predict what are the most viable evolutionary paths - such as which metabolic systems are more likely to change in what ways - in response to a given environment change?
And you make this claim based upon what? Seems to me, personal incredulity does not an argument make.
Well, there goes ID.
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