Symposium honors career of UW-Madison biochemist

Biochemists will gather on the UW-Madison campus for the 35th Steenbock Symposium on June 26-28 to discuss advances in nuclear magnetic resonance (NMR) spectroscopy, a laboratory technique that gives scientists important structural information about biological molecules.

The theme of the symposium, hosted by the Biochemistry Department, honors the career of UW-Madison biochemist John Markley, director of the National Magnetic Resonance Facility at Madison (NMRFAM). Markley, who is the university’s Steenbock Professor of Biomolecular Structure, is known internationally for his work advancing this powerful scientific tool.

“NMR spectroscopy has undergone an enormous transformation since John started his career in the early 1970s. It’s basically been revolutionized during that period,” says senior scientist Milo Westler, who manages the NMRFAM and helped organize the symposium. “The plan for the symposium is to follow the course of John’s career, highlighting the advances in the various areas of NMR spectroscopy that he’s been involved in.”

Biochemists, geneticists and other scientists routinely use NMR spectroscopy to visualize the biological molecules that underpin life-our proteins, nucleic acids and small metabolites. The technique relies on a very large magnet and radio waves to deduce the location of a molecule’s atoms and thus its shape. It’s a popular method for solving the three-dimensional structure of proteins, but it’s also used to monitor protein folding reactions and observe the interaction of proteins and other biomolecules.

But NMR’s capabilities have not always been so vast. One of its chief limitations is that it can only detect atoms with a nuclear spin. When Markley began his career, NMR was virtually useless for observing the most common forms of carbon and nitrogen in the environment, carbon-12 and nitrogen-14. As a young faculty member at Purdue University, Markley figured out ways to grow organisms in the presence of NMR-observable isotopes-carbon-13 (13C) and nitrogen-15 (15N)-to produce biomolecules that were easy to visualize through NMR, a process known as isotope labeling.

“Now people do isotope labeling all the time,” says Westler, who was one of Markley’s first graduate students at Purdue. “John has contributed in a lot of ways, but I really think that was one of his major contributions.”

Probably equally important, notes Westler, is that Markley founded two NMR facilities during his career, the first at Purdue in 1977, the second at UW-Madison when he joined the biochemistry faculty in 1984. Establishing and maintaining this sort of facility is no easy task. NMR machines can cost upwards of $5 million, and the most powerful ones are so large researchers must climb a spiral staircase to get to the sample chamber at the top. Yet Markley has managed to win impressive grants that have enabled the NMRFAM facility-and its staff of 11-to participate in important national initiatives to solve protein structures and understand the human metabolome.

In 1988, Markley also founded the Biological Magnetic Resonance Data Bank (BMRB), which serves as the worldwide repository for biomolecular NMR data and is a partner in the Worldwide Protein Data Bank. Eldon Ulrich, the BMRB Director, is the other co-organizer of the symposium.

These facilities represent tremendous resources for scientists on campus and off. Industry and academic scientists regularly send samples to the NMRFAM for analysis, and Markley participates in an ever-shifting array of research collaborations with faculty from around the world.

“John has contributed to the career of so many young scientists just because the facility is here,” explains Westler. “When an assistant professor gets started, they don’t have an NMR machine. But they come through here, get the data they need and publish papers so that they can write grants, get their own machines and move on.”

Established scientists tap into the facility, too. One of the speakers at the upcoming Steenbock Symposium, UW-Madison biochemist Hector DeLuca, will discuss how his lab is using NMR spectroscopy to look for changes in the shape of the vitamin D receptor protein when it binds to different vitamin D analogs created in his lab, information that will help DeLuca better understand how these promising drug candidates function in the human body.

Like DeLuca, all of the speakers at the Steenbock Symposium have a connection to Markley. They are his collaborators — old and new — and his former graduate students and postdocs. “Everybody we invited to speak said they’d be happy to do it,” says Westler. “John is very well liked in the community.”