Device to Give Peek into Protein Structures

September 11, 2009

BY: BILL SNYDER

Vanderbilt University researchers have received a $3.9 million federal stimulus grant to purchase a powerful analytical instrument that will greatly accelerate their studies of complex protein structures.

The ultra-high field, 900 megahertz nuclear magnetic resonance (NMR) spectrometer is a much more powerful version of instruments that have been used for years to determine the three-dimensional structures of proteins and protein complexes.

“This will enable a substantial advance in analyzing the structure, dynamics and function of large membrane and soluble proteins, multi-protein cellular machinery and DNA damaged by environmental toxins,” said Walter Chazin, Ph.D., director of the Vanderbilt Center for Structural Biology and one of several faculty members who will use the new instrument.

Charles Sanders, Ph.D.

Charles Sanders, Ph.D.

“The impact will be felt broadly,” he added, “not only within the center, but also across the biomedical research community (at Vanderbilt). A wide range of investigators are studying cancer, diabetes, heart ailments, and many others diseases.”

Charles Sanders, Ph.D., is principal investigator of the grant, one of 13 stimulus grants, totaling $8.9 million, which have been awarded to Vanderbilt by the National Science Foundation (NSF) since June.

Sanders, professor of Biochemistry, uses NMR methods to determine the structure of large membrane proteins such as G protein-coupled receptors, which are targets for about half of all pharmaceuticals.

Chazin, Chancellor’s Professor of Biochemistry and Chemistry, is applying NMR methods to better understand signaling pathways, protein turnover and multi-protein machines responsible for DNA replication, damage response and repair.

Other co-investigators of the NSF grant are:

• Brandt Eichman, Ph.D., assistant professor of Biological Sciences and Biochemistry, who studies proteins involved in DNA replication and repair;

• Stephen Fesik, Ph.D., professor of Biochemistry, who is leading a new cancer drug discovery program;

• Billy Hudson, Ph.D., Elliott V. Newman Professor of Medicine, who is using NMR to determine the structures of novel protein cross-links in collagen proteins in the kidney;

• Andrzej Krezel, Ph.D., associate professor of Biological Sciences, who is focusing his structural and biochemical inquiries on the bacterium Helicobacter pylori, the strongest known risk factor for stomach ulcers and gastric cancer;

• Jens Meiler, Ph.D., assistant professor of Chemistry and Pharmacology, who is studying the relation between chemical structure and biological activity in order to design more efficient and more specific drugs; and

• Michael Stone, Ph.D., chair of Chemistry, who uses NMR to study DNA damage induced by mutagenic chemicals, a major cause of genetic abnormalities that contribute to human cancers.

“This new instrumentation will facilitate new avenues of research … particularly with regard to delineating the chemistry of complex structure-activity relationships in biological macromolecules,” Stone said.

It also “will open the door for recruitment of outstanding new investigators to our research community,” added Michael Waterman, Ph.D., chair of the Department of Biochemistry, and it will improve the quality of research training for students pursuing advanced degrees.

Other NSF stimulus grants have been awarded to researchers in the departments of Physics and Astronomy, Electrical Engineering and Computer Science, Mathematics, and Earth and Environmental Sciences.

Vanderbilt researchers also have received 90 stimulus grants from the National Institutes of Health (NIH), totaling more than $25 million for the current fiscal year.

The funding is being provided through the American Recovery and Reinvestment Act, signed into law by President Obama on Feb. 17, which is designed to help stimulate the national economy through, in part, “the support and advancement of scientific research.”

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