November 15, 2004

Nuclear Magnetic Resonance Facility Opens
by Lucinda Weiss

A new Nuclear Magnetic Resonance (NMR) facility at UConn is providing powerful research tools for biologists, chemists, and pharmaceutical scientists, and supporting a growing collaboration in structural biology between the Storrs campus and the Health Center.

The facility, which opened Nov. 4, is housed in the Chemistry Building and operated by the Biotechnology and Bioservices Center. It has three NMR spectrometers, ranging in magnetic field strength from 300 MHz to 600 MHz. Biologists use NMR instruments, which are likened to big superconducting magnets, to study the properties of molecules.

With this technology they can see in high resolution and great detail the workings, three-dimensional structures, and dynamics of molecules ranging from small organic compounds to biological polymers, such as proteins and nucleic acids.

“It’s a very important technique to have,” says Andrei Alexandrescu, assistant professor of molecular and cell biology and one of three heads of the facility.

Super High Resolution

The NMR works by magnetizing the nuclei of atoms that have spin, a physical property that makes them behave like tiny bar magnets. Scientists can deduce their properties based on interactions in the strong magnetic field provided by the NMR instrument.

Martha Morton operates the new Nuclear Magnetic Resonance Facility, which opened Nov. 4 in the Chemistry Building. NMR is a powerful research tool for biologists, chemists, and pharmaceutical scientists.

Photo by Dollie Harvey

In structural biology, a growing field at UConn and nationally, scientists are using increasingly larger and more powerful NMR’s to learn about the structure of very large biomolecules, which could not easily be studied before.

Martha Morton, NMR facility scientist, says there are as many as 80 regular NMR users now in different research groups on the Storrs campus.

“NMR gives you super high resolution,” says Philip Marcus, Board of Trustees Distinguished Professor of Molecular and Cell Biology and director of the Biotechnology and Bioservices Center.

With NMR, it’s possible to look at a molecule of the influenza virus, for example, and learn from its structure whether it could infect avian or mammalian cells.

“You could only see this resolution in an NMR, not electron microscopy,” Marcus says.

“It’s an essential pillar. Without that, you’re nothing in structural biology,” says Philip Yeagle, professor and head of the Department of Molecular and Cell Biology.

For the past few years, Storrs researchers who needed NMR for their research have traveled to Farmington to the Health Center’s structural biology facility, a biological research NMR facility, separate from the magnetic resonance used at the Health Center for body imaging.

Two years ago, Janet Greger, vice provost for research and graduate education, appointed a committee headed by Yeagle to update and refocus the activities of what was then called the Biotechnology Center.

One of the needs identified was for NMR’s that would be available to all active and funded researchers. Other NMR’s on the Storrs campus – three at the Institute of Materials Science and one in chemistry, for instance – weren’t tailored for biological experiments, which are conducted with liquid rather than solid samples.

Establishing the new NMR facility – an example of the services added by the Biotechnology Center when it changed its name in June to Biotechnology and Bioservices – was a collaborative effort. Arlene Albert, professor of molecular and cell biology, and Alexandros Makriyannis, Board of Trustees Distinguished Professor of Medicinal Chemistry and Molecular and Cell Biology, obtained research grants that helped pay for the instrumentation. The University provided the facility, which was designed for the new Chemistry Building, and the School of Pharmacy and indirect grant costs provided matching funds.

“Many faculty participated in this effort,” says Greger. “Then Purchasing worked with the faculty so that three NMR’s could be purchased with funds that initially looked sufficient to purchase only two. The net result is that we have the array of NMR’s necessary, particularly in cooperation with NMR’s at the Health Center, so that faculty can be competitive in their grants.”

In addition, a cryoprobe for the 600 MHz NMR at the new facility is due for delivery in December. Cryoprobes, a recent advance in NMR technology, are used to cool the electronics used to detect the NMR signal to minus 269 degrees Celsius and offer a four-fold improvement in the instrument’s sensitivity.

Chemistry has already added to the facility its own 300 Mhz NMR instrument, which will be used to train undergraduates in the technology. Alexandrescu is teaching two graduate courses on the higher power instruments used for biomolecular NMR, including one that is taught at Storrs and relayed by televised link to the Health Center.

Complementary Research

The partnership between the Health Center and Storrs structural biologists now involves nearly two dozen investigators on both campuses, says Yeagle, director of the group.

“We’re all interested in one way or another in the architecture and action of the molecules of life,” he says, adding that this “critical mass” of researchers can establish a leadership role for UConn in structural biology.

What makes the UConn group stand out, Yeagle said, are its strengths in membrane protein structure research; a strong program of cluster computing that allows biologists to simulate molecular structures on a computer; and having the National Center for Analytical Ultracentrifugation at the Storrs campus.

A pending NIH grant application headed by Jeffrey Hoch, associate professor of molecular, microbial, and structural biology and director of the Gregory P. Mullen NMR Structural Biology Facility at the Health Center, requests an 800 MHz NMR. It would be housed at Farmington and linked electronically to Storrs.

The collaborations fostered among users of the new NMR facility reflect “the paradigm for structure biology these days,” says Alexandrescu. “It has become more integrated, with various disciplines and techniques complementing each other.” Alexandrescu works on protein structure and folding, and studies the interactions of proteins through NMR.

Amy Howell, associate professor of chemistry and another head of the NMR facility, studies small molecules that have interesting biological activity. In one study, her group tried to improve on some of the biological features of ocetanocin, an antiviral compound that has shown anti-HIV activity in models, although not clinically. They ended up with a totally unrelated compound. The NMR helped them identify the unexpected product and understand why the reaction behaved differently than expected, she says.

Spiro Pavlopoulos, assistant professor of pharmacy and the third head of the facility, says the new NMR facility has enabled his group to obtain in 30 minutes far more data in an experiment than they were able to generate in 16 hours before.

There are plans to add a Bio- informatics Facility to the center that will aid in the analysis of the huge amounts of data generated by the NMR’s.