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Vanderbilt Awarded $16.5M to Determine how Toxic Agents Affect Human Cells

Published: Friday, March 07, 2014
Last Updated: Wednesday, March 12, 2014
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As part of the Rapid Threat Assessment program, the team will seek to develop mass spec methods for quickly determining how potentially toxic agents affect human cells.

Vanderbilt University has been awarded a Cooperative Agreement with the Defense Advanced Research Projects Agency (DARPA) and the Army Research Office (ARO) that is worth up to $16.5 million over five years.

The Vanderbilt Agreement is led by Richard Caprioli, Ph.D., Stanford Moore Professor of Biochemistry, director of the Mass Spectrometry Research Center (MSRC), and principal investigator of a National Institutes of Health grant (GM103391) that in 2011 established a National Resource in Imaging Mass Spectrometry.

“In the second half of my career, I want to take some of the … really extraordinary things that can be done in research labs, and … bring them into the public domain on problems that can directly help (people),” said Caprioli, who joined the Vanderbilt faculty in 1998.

The Vanderbilt Agreement governs research that will be conducted in up to four phases. At the end of each one, the milestones and the metrics “get tougher and tougher,” said Caprioli, a pioneer in mass spectrometry techniques who also is professor of Medicine, Chemistry and Pharmacology.

A trans-institutional effort, the Vanderbilt project consists of three teams:

The analytics team – co-led by Jeremy Norris, Ph.D., research assistant professor of Biochemistry who also serves as project manager, and John McLean, Ph.D., Stevenson Associate Professor of Chemistry in the College of Arts and Science.

Other faculty team members include Kevin Schey, Ph.D., professor of Biochemistry and director of the MSRC Proteomics Lab, and Brian Bachmann, Ph.D., associate professor of Chemistry and Biochemistry.

The biology team – led by Eric Skaar, Ph.D., MPH, Ernest W. Goodpasture Professor of Pathology, director of the Division of Host-Pathogen Interactions and director of the Program in Microbial Pathogenesis in the Department of Pathology, Microbiology and Immunology.

Borden Lacy, Ph.D., associate professor of Pathology, Microbiology and Immunology and of Biochemistry, is a faculty member of this team.

The cell automation team – led by John Wikswo, Ph.D., the Gordon A. Cain University Professor and director of the Vanderbilt Institute for Integrative Biosystems Research and Education, who also is leading a multi-institutional, federally-funded effort to develop a “microbrain bioreactor” to aid drug development.

The cell automation team will develop methods for freezing cells exposed to toxic agents “very fast … in 50 milliseconds in some experiments,” Caprioli said.

“We’re going to grow human cells on slides … and they’re going to be exposed to the toxins and will be analyzed using our scanning, laser-based mass spectrometry technologies … to get a very rapid assessment of what’s going on in those cells at the molecular level,” he said.

These include MALDI IMS, an imaging mass spectrometry technology developed at Vanderbilt that is being used to study how changing gene expression affects production of proteins and metabolites important in cellular function and regulation.

Instrumentation that will be used for these studies includes a new 15.5 tesla FTICR mass spectrometer that was installed in Caprioli’s lab on the ninth floor of MRB III last fall (15.5 tesla is roughly 200,000 times the strength of the earth’s magnetic field), and a 9.4 tesla instrument.

“The opportunity is amazing,” Caprioli said. “It makes you get up in the morning with great enthusiasm and say, ‘Let’s get there and do this. This is worth doing.’”

The Vanderbilt Agreement is one of three awarded recently through DARPA’s Rapid Threat Assessment program. The other institutions are the University of Colorado Boulder, and George Washington University in Washington, D.C.

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