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Systems Studies Reveal Regulatory Networks in Bacterial Species

NEW YORK (GenomeWeb News) – A pair of studies by researchers involved in the Bacillus Systems Biology, or BaSysBio, project are providing an exceptional level of detail into the networks regulating transcriptional and metabolic pathways in Bacillus subtilis under different environmental and nutritional circumstances. Both studies were published online today in Science.

The findings are of interest not only for understanding bacterial adaptation and evolution, researchers explained, but also from a manufacturing point of view, since the soil bacteria species is used to produce vitamins, enzymes, and other metabolites in the pharmaceutical, agricultural, and food production industries.

"Besides their scientific novelty, these two studies also represent a potential blueprint for bacterial systems biology," INRA researcher Philippe Noirot, senior author on one of the studies and co-author on the other, said in a statement. "Our work will potentially make B. subtilis an even more efficient producer of enzymes."

"The results and approaches used in our studies suggest it is now possible to design specific experiments to unravel other, previously more intractable, cellular processes," he added.

In the first of the studies, Noirot and his colleagues used tiling microarrays to look at the collection of sense and antisense transcripts expressed by B. subtilis bacteria grown in 104 different conditions. They found that while some 85 percent of the bug's annotated coding sequences were highly expressed in at least one of the conditions tested, for instance, just 3 percent or so had pronounced expression under all of the conditions.

From there, the team went on to define and map transcription units and so-called regulons involving almost 3,000 promoters and an arsenal of sigma factor proteins that mediate RNA polymerase binding to gene promoters.

Along with the 4,200 or so known genes in the B. subtilis genome, the group also found transcripts representing more than 500 possible new genes as well new regulatory RNA candidates.

For a second BaSysBio study, a team led by investigators in Switzerland and France profiled gene expression, promoter activity, chromatin binding patterns, metabolite concentrations, protein levels, and more in B. subtilis cultures that were switched back and forth between two different carbon sources.

"To elucidate the dynamic interplay between metabolic and regulatory networks systematically, we investigated dynamic shifts in availability of the preferred carbon sources, glucose and malate, of the bacterium Bacillus subtilis," Swiss Federal Institute of Technology Zurich researcher Uwe Sauer, co-corresponding author on that study, and colleagues explained.

That group used computational analyses and modeling to bring their data together in a way that allowed them to discern everything from gene regulatory networks to shifts in transcription and metabolic output.

"Our systems approach helps reveal how previously known regulatory mechanisms are combined to effect nutritional transitions," the study's authors wrote. "Despite more than half of the B. subtilis gene complement being involved in the adaptive response to glucose, our methodology could discern key regulatory events."

"The work represents a conceptual step forward in how to assess and understand cellular adaptation to new situations that is fundamental to basic science as well as applications in biotech and medical research," Sauer said in a statement.

In a perspectives article in the current issue of Science, researchers from the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, said the new studies "describe how the bacterium Bacillus subtilis achieves adaptation at an unprecedented level of detail and breadth."

"Similar studies in other organisms will be imperative to understanding long-standing fundamental questions in biology," corresponding author Madan Babu and colleagues concluded.

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