November 12, 1999

Major structural biology initiative launched

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Walter Chazin, Ph.D., directs the new Vanderbilt Structural Biology Program. (photo by Dana Johnson)

Major structural biology initiative launched

Walter J. Chazin, Ph.D., plans to put Vanderbilt on the map as a premier site for structural biology research.

There is broad excitement across the Vanderbilt campus that Chazin has joined the faculty as professor of Biochemistry and director of the new Structural Biology Program, a major initiative that bridges the university and the medical center. He comes to Vanderbilt from the Scripps Research Institute.

"Not only does Walter Chazin bring a world-class research program to Vanderbilt, but he also will provide dynamic leadership for the Structural Biology Program," said John H. Venable, Ph.D., associate provost. "The program and facilities he develops will serve the interests of many departments and bring prominence to the university."

Michael R. Waterman, Ph.D., Natalie Overall Warren Distinguished Professor and Chair of Biochemistry echoed those sentiments.

"Walter Chazin is a well-known scientist and leader in the study of protein structure by NMR. This alone makes him a valuable addition to our campus. But in addition to that, Walter's vision for the development of the Structural Biology Program made him irresistible as the top candidate for the director position."

That vision includes two main elements consisting of a core of approximately 12 investigators focusing on atomic resolution structural biology — getting molecular structures down to the atom level — and a resource center to promote molecular research across the campus.

Chazin explains that being able to "see" the location of atoms that make up each molecule leads to understanding, at the most fundamental level, how molecules work when they perform biological functions in the body.

"Only by understanding how biological molecules work, how they interact with each other and with drugs, can we make rational choices in the development of new therapeutics that affect these molecules and their functions," Chazin said.

Think about trying to fix an engine without knowing anything about the parts inside; what they look like, how they fit together, what they do. Structural biologists are working to answer these kinds of questions for the engine parts of life.

The dozen researchers in the Structural Biology Program core will include investigators from each of the three primary disciplines of atomic resolution structural biology: x-ray crystallography; NMR spectroscopy; and computational biology. The faculty currently includes three x-ray crystallographers and three (including Chazin) researchers who use NMR. Chazin will recruit the rest of the core group during the next five years.

The resource center will have expertise in the three primary disciplines as well as in sample production — making protein of appropriate quantity and quality for structural biology experiments. Four Ph.D.-level scientists will run the resource center and work as a team to assist other investigators in developing structural biology projects.

"The resource center is like a belt around the central core and will act as the interface between the core researchers and the rest of the campus," Chazin said. "It will have a mandate to stimulate molecular-level thinking and promote the development of structural biology projects throughout the campus.

"There's a long way to go to take a project from its conception in a biology lab to actually realizing a structural biology result. Any researcher on the campus will be able to meet with the resource center team for advice on how to proceed with a project idea."

After talking to an investigator to understand the biological questions and the protein material starting point, the team will determine whether the questions require a computational or experimental approach, and what type of experimental approach would be best.

"Through the resource center, the Structural Biology Program will let those investigators who are currently inexperienced with structural tools begin to address biological problems at the level of single molecules or molecular complexes," said Lee E. Limbird, Ph.D., associate vice chancellor for Research. "It will offer the opportunity for strategic design of structural experiments, overproduction and purification of molecules to be analyzed by x-ray crystallography or NMR spectroscopy, and the much-needed computational tools to analyze, interpret, and work further with the data developed."

The Structural Biology Program will bring, for the first time, computational biology expertise to Vanderbilt. Jarrod Smith, Ph.D., one of Chazin's former graduate students, is already on board to run the computational biology division of the resource center.

"I think the computational part of the resource center will be the most actively and widely used, because it's not only for structural biology, it's for molecular thinking in general. I see it as a clearinghouse for finding out where to go for computational resources, both within the structural biology resource center and elsewhere on campus," Chazin said.

"The intent is for the resource center to draw investigators in. Students, postdocs, and faculty will be able to learn how to run programs where they can pull up coordinates of a structure, manipulate it on screen, and use the analysis to design their own experiments. That's really an important part of how we will bring a greater sense of molecular thinking to the campus."

The Structural Biology Program will occupy space in Medical Research Buildings I and II until it finds a permanent home in a new research building with shared space for university and medical center investigators. The round building outside Stevenson Center is being renovated to house the Vanderbilt Biomolecular NMR Center.

In the current floor plans for the new research building, Chazin points out how the large space will be shared by the resource center and several of the core investigators.

"I'm pushing a whole new concept — that because the disciplines of structural biology are so very complementary, they need to be better integrated with each other. I'm convinced that the structural biology of the future will not be based on the technique per se," Chazin said. "This idea will be fostered by the space itself, with different research groups being pell-mell in the same laboratory space.

"This level of cooperation and interaction will really make the Vanderbilt Structural Biology Program unique, and I think it will be one of the things that puts us on the map."

Others agree.

"We are optimistic that within five years, Vanderbilt will be well established as a major player in structural biology," Waterman said.

As Chazin implements his vision for the Structural Biology Program, he continues to run his own active research program. Chazin is well known for structural studies of molecules involved in calcium signal transduction. He has also analyzed the Holliday junction in DNA recombination and the interaction of anti-tumor drugs with DNA.

A new focus in his laboratory is the repair of damaged DNA. He is particularly interested in the role of the molecule replication protein A as a coordinator of the stepwise repair process. Understanding DNA damage and repair will yield important insights to what goes wrong in cancerous cells and could point to new therapeutic possibilities.

Chazin received his Ph.D. degree in Chemistry in 1983 from Concordia University in Montréal. He was awarded a Québec Ministry of Education Postdoctoral Fellowship to extend his research training at the Biophysics Institute in Zürich, Switzerland. In 1986, he joined The Scripps Research Institute as a research associate and advanced to the tenured associate professor II level.

He is excited about the possibilities for the Structural Biology Program.

"Vanderbilt is the ideal place to try and realize this vision and my dream for this kind of integrated program. There's a tradition of collaboration here. It's built into the culture," Chazin said.