Spectrometer penetrates molecular-level mysteries

New $5 million device will enable Jim Prestegard and researchers at UGA’s Complex Carbohydrate Research Center to do groundbreaking work on diseases such as cancer

B Y - S H A R R O N - H A N N O N

he Complex Carbohydrate Research Center is tucked along a curve of land that slopes down to the Oconee River. Past the expanse of glass at the far end of the lobby, a granite terrace with benches provides a view of the river below, brown and narrow as it snakes its way through the trees. The setting is impressively tranquil, belying the fact that the building is less than half a mile from the Athens Perimeter exit for College Station Road—and that science, not nature, is the focus here.
The Georgia Research Alliance helped recruit Prestegard to UGA from Yale and contributes funds to support his research.
The mammoth new facility—three stories high and nearly 140,000 square feet—provides an anchor for what one day may be a vast research park along the aptly named Riverbend Road, just south of the main UGA campus. The first large-scale research building to be funded by the UGA Real Estate Foundation, the new CCRC was completed in fall 2003 and officially dedicated on Feb. 11 (see p. 1). But the move-in process is still under way.

“It’s a good lesson in patience,” says Jim Prestegard, a Georgia Research Alliance Eminent Scholar who works with nuclear magnetic resonance (NMR) spectrometers. Prestegard is awaiting the arrival of a 900-megahertz spectrometer that is slated for shipment from England in late March or early April. It will come by boat and take three weeks to get to Athens, then at least another month to set up.

There’s also the matter of getting the spectrometer into the building. On the second floor of the CCRC is a small windowed landing labeled “NMR overlook.” From there, visitors can look down into the large hall where the spectrometer will be installed. In the tiled ceiling high above that room is the massive panel that will be removed to allow the spectrometer to be lowered by crane—very carefully—into the facility.

The 900-MHz spectrometer is one of only four funded in an initial round of competition for grants from the National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health. Only a few such spectrometers are currently being installed around the world.

As might be expected, such a piece of equipment comes with a hefty price tag. To obtain the spectrometer, Prestegard made a presentation to the Georgia Research Alliance board of trustees, which includes prominent business leaders and the presidents of the state’s research universities. Prestegard made the case that a $1 million investment by GRA would make UGA competitive for external funding for the remainder of the $5 million cost.

“I knew this would be an important step in keeping research at the cutting edge in Georgia,” says Prestegard, “and I am delighted the GRA board felt the same way.”

After securing GRA support, Prestegard was able to land the NIGMS grant for $4 million with an additional $1.5 million operating budget over the next five years, thus establishing the Southeast Collaboratory for Biomedical NMR.

“We’ll be working with 30 investigators at 18 institutions in the Southeast,” says Prestegard. “This is a very skilled group of researchers and we’ll pool our expertise to accelerate the development of new technologies.” Support from the Georgia Research Alliance also was key in drawing Prestegard to UGA in the first place. A noted researcher in structural biology, he had enjoyed a 27-year career at Yale when he was lured to Athens in 1998 as UGA’s 6th GRA Eminent Scholar (there are now 12).

“Jim is a team player and team builder who enjoys the respect and admiration of his colleagues,” says UGA Vice President for Research Gordhan Patel. “He helped create programs that bring in significant funding and he also made it easier for the commercial sector to interact with the University. The Georgia Research Alliance plays a crucial role in helping us compete for and hire faculty of his ability.”

What attracted Prestegard to UGA and the CCRC was the chance to work within a scientific community with a high degree of interdisciplinary collaboration.

Scientists at UGA’s Complex Carbohydrate Research Center recently relocated their offices and labs to a new and significantly larger facility on Riverbend Road. Though not an easy move, the gain in space is worth it.

At nearly 140,000 square feet, the new CCRC building is more than three times the size of the original CCRC building that opened in 1989. The size of the new facility reflects the growth in scope of the research being carried out there. When UGA recruited Peter Albersheim and Alan Darvill to establish the CCRC, they brought with them a 16-member research team from the University of Colorado. Today, more than 200 scientists, students, and staff work in 15 interdisciplinary research groups.

CCRC scientists study the structures and functions of the complex carbohydrates of plants, microbes, and animals to determine the role of carbohydrates in growth and development, host-pathogen interactions and disease processes. Ultimately, such research can lead to advances in diagnostic techniques, vaccines and remedies for disease.

The CCRC research groups develop and use advanced analytical techniques–among them nuclear magnetic resonance (NMR) spectroscopy. The new building contains an NMR spectrometer “suite” designed to accommodate a new Varian Unity Inova 900-megahertz spectrometer–one of the few to be found anywhere in the world.

“Much of academe is very focused in pursuit of intellectual goals by individuals,” he says. “Places like Yale emphasize that. But I saw the move to Georgia as an opportunity to build my area of science in a way that involved a broader community. I thought I could have more impact in this kind of environment.”

Prestegard is involved in several important research partnerships. He is one of a team of scientists led by B.C. Wang, another of UGA’s GRA eminent scholars, working on a pilot program to analyze proteins coded by part of the human genome and the entire genomes of two representative organisms. The project is funded under a major initiative developed by NIGMS.

He is also working with UGA colleague Michael Pierce, a professor of biochemistry and molecular biology, on research to further the development of new—and potentially revolutionary—cancer treatments. The research is funded by the American Cancer Society and the National Cancer Institute.

In his work with Pierce, Prestegard uses NMR techniques to provide detailed information on how potential building blocks for drugs bind to proteins that Pierce identifies and isolates. The information will help scientists design molecules that could prevent the spread of cancer in humans.

“The way to make an effective disease inhibitor is to know structural information about the interaction between proteins and potential drug candidates,” says Prestegard. “The NMR technique presents information that will enable scientists to develop drugs that bind more tightly to proteins and, therefore, devise faster and more effective treatments for disease.”

Nuclear magnetic resonance spectroscopy is a diagnostic tool that operates on the same principle as magnetic resonance imaging (MRI). But instead of looking at structures on the anatomical level, researchers use NMR spectroscopy to study structures at atomic levels.

“I’ve never found a perfect way to explain my work,” Prestegard admits. “I use NMR to get atomic-level pictures of biologically important molecules including proteins, nucleic acids and carbohydrates. We want to gain an understanding of how molecules function—for example, how proteins recognize and interact with carbohydrates on the surfaces of cells.”

The power of NMR spectrometers increases with the magnetic fields at which they operate and the radio frequencies used to observe magnetic nuclei within proteins at these fields. “There are tremendous advantages to working at higher and higher magnetic fields,” says Prestegard.

An 800-MHz spectrometer—which creates a magnetic field strong enough to erase credit cards and pull keys from pockets—is already set up in the new CCRC, in one wing of the L-shaped room where the 900-MHz spectrometer also will be housed. The room is currently littered with boxes of partially unpacked equipment that will be used to install the larger spectrometer, which, according to Prestegard, looks something like a “lunar lander” (see photo on p. 28) and weighs three times as much as the smaller version.

While awaiting the new spectrometer, Prestegard is busy teaching and traveling. Within the first few months of the year, he will have been to a conference, delivered major lectures at UC-San Diego and UNC-Chapel Hill, and attended the annual meeting of the American Chemical Society. He is team-teaching a graduate course in biomolecular nuclear magnetic resonance to students at UGA, Georgia Tech, and Georgia State via a teleconferencing network. He is also, for the first time, teaching an Honors biology seminar on how new proteins are discovered and characterized.

“The course helps me look beyond the constricting boundaries of a lower-level biology course and ask how and why,” says one of his Honors seminar students, Kurinji Pandiyan, a freshman with a double major in genetics and chemistry. “It has helped me appreciate biology as a science that can stimulate one intellectually.”

Anita Kishore, a Ph.D. student in chemistry who came to UGA to join Prestegard’s lab, confirms his ability to get others excited about research. “It’s like his mind never turns off,” she says. “He has this amazing ability to generate scientific ideas—and even if they don’t all work out, the fact that he has so many just blows us all away sometimes.”

Where Prestegard’s ideas will eventually lead is hard to predict. “The things we do with NMR technologies,” he says, “tend to have an impact 10 years down the road.”

But the importance of such research is being increasingly recognized. The 2002 Nobel Prize in chemistry was shared by Kurt Wuthrich, a professor of biophysics at the Swiss Federal Institute of Technology in Zurich, who uses NMR to map the structure of proteins. Prestegard pulls a thank-you card from Wuthrich from a shelf in his office to illustrate the worldwide network of those engaged in the field.

“Georgia really has national and international visibility,” he says. “Thanks to the Georgia Research Alliance, others see this state as a place with a very sound investment in high technology.”

Sharron Hannon is special assistant to the UGA provost. A similar version of this story appeared in the 2003 Georgia Research Alliance Annual Report.

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