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Academic-Industry Initiative Will Develop Bioinformatics Tools to Model Living Cell

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SEATTLE--A team of researchers led by Bob Franza of the University of Washington here is developing bioinformatics tools to create a quantitative model of the living cell.

The Cell Systems Initiative was launched late last year, and thus far has attracted the support of two corporate backers who would like to mine the data it generates to identify new drug targets. Franza, a research professor in the School of Medicine's molecular biotechnology department, is discussing potential collaborations with several other companies.

The goal, according to Franza, is to understand the stages of a cell's development. "How does one stage know when it's supposed to start and stop?" Franza asked. "How do we reconstruct the temporal process?" A complete model of the living cell will need to be understood not as parts, but as components of a continuous system, he said. To that end, the initiative also aims to build a computational infrastructure that can manage the entire dynamic system of data collection and integration.

Industry support

In February, Seattle-based Immunex pledged $2.1 million to the initiative and access to several senior scientists over the course of three years. A month later, Isis Pharmaceuticals of Carlsbad, Calif., said that it would contribute bioinformatics tools and intellectual and financial resources. Isis would not disclose the amount of its financial investment, but Franza acknowledged it is substantial.

The most important contributions, he stressed, are the scientific collaborations these companies can provide. While eight people are presently working at the project's rented lab space, several Immunex researchers are collaborating with the initiative's systems specialists to develop a representation of T-cell/dendritic cell interactions, and about 12 Isis bioinformaticists divide their time between the initiative and their employer's own projects.

Isis has "exactly the right kind of high-quality bioinformatics tools to study how RNA is being made, how much, and at what rate," Franza said. Such tools can be helpful to researchers looking to contrast the effects of a subtle disturbance to a cell with the blunt blow that gene removal causes.

Bioinformaticists from Isis will work with scientists at the University of Washington to adapt MetaGraph--the company's proprietary bioinformatics database--to assimilate and manage large quantities of genomic data and find relationships in complex data arrays. Metagraph will sit on top of Moulage, a system already developed by the Cell Systems Initiative's computer scientists (http://cellworks. washington.edu/pub/docs/systems.html).

Their system will also automate data collection in a "pervasive but not intrusive" way. A researcher should not have to run to a keyboard or take a separate step to record when the experiment was performed or by whom, Franza said. Data and environmental circumstances will be recorded as work is done, so that when scientists have results that don't match, "we'll be able to say more than just, But I did the same thing," Franza said.

"No current tool sufficiently describes the complex phenomenon of biological life," said David Ecker, VP and managing director at Ibis Therapeutics, a division of Isis. "What we're doing is a step beyond anything that exists."

Franza concurred: "If a bioinformatics tool exists off-the-shelf that works, we use it. But we looked far and wide, and we realized we were going to have to build many of our own tools."

Franza noted that the tools developed by the initiative team will be made freely available on the web. But, he added, if someone wanted to commercialize them, "we'd readily negotiate fair licensing agreements."

--Melissa Mertl

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