Big magnet to bolster lab

The hidden world of biological macromolecules — the proteins, enzymes, nucleic acids, complex carbohydrates, and hormones that underpin all life — will soon become a little less murky with the help of the mother of all NMR magnets.

In biology, an increasingly important window to the chemical interactions of the molecules responsible for everything from muscle contraction to antibiotic activity is nuclear magnetic resonance (NMR) spectroscopy. NMR technology depends on large magnets to listen in on the chemical cross talk between molecules at work, and the stronger the magnetic field the more detail can be gleaned from these conversations.

Now, with support from the National Institutes of Health, UW–Madison’s National Magnetic Resonance Facility will be home to a machine capable of generating the largest NMR-quality magnetic field possible with current technology.

A $5 million award from NIH’s National Institute of General Medical Sciences paves the way for the fall deployment of an 11-ton, 900-megahertz NMR magnet that will position the lab to remain as one of the top NMR research facilities in the world, says biochemistry professor John Markley,

“This system will enable us to examine biological processes we haven’t been able to attack before,” Markley says.

Markley, who led the effort to bring this technology to Wisconsin, is one of 36 researchers from around the country with grant funding from the National Institute of General Medical Sciences who plan to use the power of the new instrument to advance their research.

The projects span a range from more applied to fully basic research. For example, one scientist hopes to use the new spectrometer to determine the structure of an abnormal protein that predisposes some people to cancer. The hope is that knowledge of the structure will suggest approaches to controlling the disease. Another scientist will use the machine to investigate one of the fundamental reactions involved in RNA splicing. “This study could yield information for the next generation of biochemistry textbooks,” Markley says.

The power of the new machine, Markley says, resides in its ability to help scientists determine the three-dimensional structures of biomolecules and understand how they work. Many proteins of interest to these scientists are potential drug targets,” says Markley, and the 900-MHz device holds the potential to reveal subtle structural nuances, insight that could pave the way for new drugs to treat human and animal diseases.

“You can find out what part of the protein a drug binds to, or see how the drug changes the protein,” Markley says.

NMR spectroscopy works by using radio waves to excite transitions in the spins of nuclei in the atoms that make up molecules. “Molecules contain nuclei that can be thought of as tiny spinning magnets,” Markley explained. “A magnetic field causes the nuclei in the molecule to rotate around that field, just like a gyroscope rotates in the Earth’s gravitational field. If we excite with the frequency of this rotation, we gain the information needed to determine the chemical environments of the nuclei and the overall structure of the molecule and how it is folded up. With the new magnet, the radio frequencies we will be using are 900 MHz, a frequency commonly used in cordless telephones.”

After delivery in September, the new machine will be the eighth operational device in the lab used by scientists from around the country.

“This new grant enables us to hire additional staff members to support an enlarged user base,” Markley says. “The technology is driven by the needs of our users, and these visiting scientists keep us on our toes. They’re interested in using the latest data collection methods, and they bring us their toughest and most important research problems. This is a great source of excitement and intellectual challenge for me and our staff.”