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CSIRO-Led Team Adopts Biolog's Cell-Array Platform for Wheat Toxin Study


Researchers at Australia's Commonwealth Scientific and Research Organization this month published a pair of papers in two separate journals describing how they used Biolog's cell-based microarray assays to study a fungal toxin that commonly attacks wheat.

Appearing in the online editions of Fungal Genetics and Biology and Microbiology, the papers describe the use of Hayward, Calif.-based Biolog's Phenotype Microarray platform to research secondary pathways in Fusarium graminearum, a wheat pathogen responsible for head blight and worldwide crop losses.

During the infection process, the fungus produces a trichothecene toxin called deoxynivalenol. Though the toxin is produced at high levels during wheat infection, researchers were previously unable to reproduce it in the lab.

Using Biolog's platform and a fluorescent protein label, the CSIRO group, led by Donald Gardiner, cultured the fungus in a variety of different stress and nutritional conditions. They were able to determine that the factors for inducing toxin synthesis are made possible by the presence of specific nitrogen compounds and low extracellular pH.

Biolog CEO Barry Bochner told BioArray News this week that the study demonstrates the adoption of the firm's cell-screening platform by agricultural biotechnology customers and, more generally, by laboratories performing research studies of toxin production by secondary microbial pathways.

The CSIRO researchers, based in the organization's labs at the University of Queensland in Brisbane, "were asking a very specific question to understand what the magical conditions are that turn on production of toxin in a fungus are," said Bochner.

"Our products are well known and widely utilized in agbio microbiology. The PM platform provides scientists with a way to put a cell into 2,000 different culture conditions where you can screen for induction of secondary pathways," he said. This particular capability has "important implications also for biodefense research, antibiotic research, and, more generally, bioprocess development where laboratories are trying to coax cells to produce higher levels of some chemical of value or importance."

Biolog launched its Phenotype Microarray cell-screening platform in 2001. The platform consists of microarray plates that allow users to culture and screen up to 2,000 cell assays, a bifunctional incubator and reader, and software analysis tools.

"We measure whether cells produce energy with colorimetric readout and with our technology you can measure [the] level or activity of thousands of cell pathways," Bochner said of the platform.

Since the launch, Biolog has progressively evolved from studying "easy bacteria" to "more difficult bacteria" like Mycobacterium tuberculosis, Bochner said. In recent years, the firm has also expanded its assay capabilities to facilitate studies of fungal as well as mammalian cells, including human cells, he said.

The CSIRO study is one example of using PM technology to study secondary pathways. Another example, published in April, a group at Wyeth Research published a paper in the Journal of Microbiological Methods by a scientist at Wyeth Research, used Biolog's array platform to determine culture conditions that yielded for higher levels of antibacterial chemical production by fungi.

Biolog has ongoing efforts to reach groups from academia and industry that are seeking answers to such biological questions. When Biolog launched its Phenotype Microarrays, most early adopters were researchers at universities and government labs, Bochner said.

The platform has also been embraced by institutions with large culture collections, primarily in the food safety area, such as the US Food and Drug Administration, the US Department of Agriculture, and the Veterinary Laboratories Agency in the UK. "They have large collections of microbial cells from food poisoning outbreaks that they wanted to compare," he said.

During the last year, though, he said the company has seen adoption from groups like those at CSIRO and Wyeth. "We are making major efforts to get our technology known in the bioprocess development space," Bochner said. "We are talking to some large agbio companies that are doing everything from specialty chemicals to biofuels, and we are increasingly working with government-funded labs and small biotechs as well."

The CSIRO study is also an example of the firm's presence outside its US base. According to Bochner, in 2008 more than half of the sales recorded by the privately held company came from outside the US, especially in China and India.

This year, hoping to capitalize on that trend, the firm will attend agbio and microbiology events across the Asia-Pacific region, including meetings in Korea, Japan, Australia, the Philippines, and Malaysia. "We have always been very strong in Asia," he noted. While Biolog sells direct in North America, it is represented by distributors in other regions.

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Rival Technologies

Though Biolog is a platform provider, Bochner said the firm is now putting its resources into "educating the scientific community towards the many important uses" of its technology. It is also trying to attract customers doing studies on human cells. He noted that Biolog has a project with Cambridge, UK-based Horizon Discovery studying metabolic and other phenotypic changes in isogenic cell lines containing cancer mutations.

Describing the phenotype microarray platform, Bochner said that Biolog is "looking into miniaturization to increase speed and throughput," and said that miniaturizing the firm's microarray plates is "probably the next direction" Biolog will take in "evolving the technology." He did not elaborate.

Companies such as Promega, Beckman Coulter, and Genomic Solutions also provide platforms to screen cells in high-throughput assays. Genomic microarray research tools, such as those sold by Affymetrix, Agilent Technologies, Illumina, or Roche NimbleGen, are seen by Biolog as complementary, rather than rival, technologies.

"Our technology is designed to provide information that is different and complementary to gene chips," Bochner said. "Gene chips provide genotypes, [whereas] our product produces phenotypes."

A "major difference" between genomic arrays and Biolog's Phenotype Microarrays is that "gene chips provide a snapshot of a cell in one instant in time and under one culture condition" Bochner said. Biolog's platform, meantime, enables users to measure phenotype and pathway activity over hours or days. "It's more like a motion picture than a snapshot," said Bochner of the difference between the research tools.