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Aided by Yates and $3.7M in Biodefense Bucks, Diversa Wields Proteomics to Pin Down Targets

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Microbial Biotech company Diversa has been using proteomics for several years. But in February 2003, its proteomics group got a boost when it was joined by about a dozen researchers — including John Yates — from the Torrey Mesa Research Institute, parts of which the San Diego-based company acquired from its partner Syngenta at the end of 2002.

Yates, who was leading the TMRI proteomics group, now heads Diversa’s proteomics effort, spending half of his time at the company, and the other half at the Scripps Research Institute, where he is a professor of cell biology. “He is the strategic leader of the group,” said Paul Oeller, who runs the day-to-day operations of Diversa’s proteomics and metabolomics department.

“At Diversa, I get to learn about the process of commercialization and what it takes to create products," Yates told ProteoMonitor in an e-mail message. The company has two product-driven divisions: bioscience products and pharma. Proteomics supports research efforts in both divisions. Bioscience focuses on bulk enzymes for agriculture, animal health, and fine chemical production. These serve “to drive our revenues and profitability forward and support the pharma products,” said Dan Robertson, a senior research fellow in Diversa’s department of enzyme technology. The pharma division seeks to develop protein therapeutics focusing on antiinfectives.

The Diversa proteomics group — which numbers 15 people, including three bioinformaticists — helps with internal research projects as well as external collaborations, in “any way that we can use this technology to generate information faster, to generate the right information more quickly,” said Oeller.

It appears to be well equipped to do so: The group boasts nine Thermo Finnigan LCQs mass spectrometers, a Micromass Q-TOF, an ABI Q-STAR, a MALDI-TOF, and a Thermo Quantum. In addition, it acquired a Thermo LTQ-FT last fall, as one of the first customers in North America, according to Oeller.

Yates said he provides technical oversight to the proteomics group, helps to decide approaches to scientific problems, and follows the field in general. However, Oeller said that “we don’t use our relationship with John as an inside track to get anything that’s ongoing in his lab [at Scripps].”

One of the group’s projects is to characterize the proteomes of Bacillus anthracis and Yersinia pestis. It is a collaboration with the US Army Medical Research Institute of Infectious Diseases and the University of North Dakota, funded with up to $3.7 million from the National Institute of Allergy and Infectious Diseases.

For the last year or so, the researchers have been characterizing proteins from several hundred membrane samples prepared from anthrax and plague bacteria grown under different conditions, said Oeller. The goal is to find surface-exposed proteins that would make good targets for antibodies, which could serve as vaccines or therapeutics. The next step will be to validate these targets by making knockouts and seeing how that affects the pathogenicity of the organisms.

But the group is also trying to push core proteomics technologies forward, he said, for example in the area of differential expression profiling. Scientists have been working on a non-labeling approach to determine quickly which peptide ions are different between two samples — using electrospray mass spec — and to identify the peptides in a second step, Oeller said.

Even before the TMRI researchers joined, the Diversa proteomics group developed a “very elegant refinement to the MudPIT technique,” said Oeller. This involves using an additional reverse phase matrix in front of the standard two resins during fractionation, which produces a 3D LC set-up instead of the usual 2D. “The number of proteins that can be identified using this method is significantly better than MudPIT in most cases,” he said.

Although no expansion of the group is planned in the foreseeable future, it remains an integral part of the company. “If you look at Diversa, we are basically a protein company,” Oeller said. “We see both proteomics and metabolomics as extremely important technologies.”

— JK

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