Systems biology meets technology

SANTA CLARA, Calif.—Basic science and analytical technology are searching for new synergies at the University of Michigan'sCenter for Translational Pathology (MCTP) through a grant of instruments and funding from Agilent Technologies. The initial target is prostate cancer, but according to the U-M's Dr. Christopher Beecher, the mechanism of action under investigation could have broad application to many solid tumor types.

MCTP is led by director Dr. Arul Chinnaiyan, whose research has already revealed metabolomic profiles of prostate cancer progression by looking at 1,126 metabolites across 262 samples of tissue, blood and urine. Now, the lab is trying to unlock the secrets of how prostate tumors gain the ability to spread. The MCTP houses cutting-edge facilities for genomic, proteomic and metabolomic analyses, the three main disciplines used in systems biology.

"We take the systems biology approach and analyze for potential new diagnostics and pathology itself," says Dr. Christopher Beecher, professor of pathology at the U-M Medical School, who came to the center from Metabolon in 2003 at Dr. Chinnaiyan's urging. The group earlier identified ETS-fusion proteins as diagnostic markers for prostate cancer and has extended this finding to all cancers.

In February 2009, Beecher co-authored a paper based on the center's metabolomic work.

"We discovered we could differentiate at the biochemical level between normal, cancerous and metastatic cells," he says. "Concentrating on sarcosine—an obscure but normal cell metabolite—the group performed a series of transformations to prove that sarcosine could induce cells to 'move'—that is, metastasize."

The collaboration between MCTP and Agilent is a result of Agilent's University Relations Program, which is based on building technology connections between the company and researchers worldwide, director Jack Wenstrand explains. Of its 100 active projects, approximately 50 are with U.S.-based partners, 25 located in Europe and 25 in Asia.

Agilent staff members—referred to as mentors—participate in writing proposals with their academic peers, after which a grants board selects those most likely to create value for the company. The program evaluates proposals based on four criteria: relationship value; relevance—is work related to one of Agilent's 13 priorities, taking the long view; thought leadership—what can be learned from the grant experience of working with a world leader; and efficiency—research results versus cost. In this case, Wenstrand notes, "The University of Michigan is doing exceptional work in systems biology."

U-M's metabolomic platform is based on mass spectroscopy, Beecher explains. Agilent is contributing a 1200 Series liquid chromatography (LC) system to be used to separate metabolites from human plasma, and a 1200 Series Rapid Resolution LC coupled to a 6530 Accurate Mass quadrupole time-of-flight mass spectrometer (Q-TOF MS) for the identification of those metabolites.

"Agilent had been looking for a specific situation involving systems biology," says Ken Miller, senior marketing director for the company's LC/MS group. "We started talking with U-M and found a huge cross-section of interest between their research and our technology."

Agilent's LC/MS instrumentation provides high-resolution data to identify differences in sample populations. The company's software tools process this information to identify metabolites or proteins.

"Agilent instrumentation is stunning in its abilities," Beecher says, "but theoretically, it can do more. With the close relationship we now have, we think we can help effect improvements in the equipment."

The focus within the center, Dr. Beecher summarizes, is to translate the work of the discovery labs into clinically useful technology to help patients. There is even a state-licensed, board-certified lab within the center to test discoveries in a broader context. "We expect to be able to make a number of discoveries in prostate cancer and to develop new techniques that will be useful universally," he adds.