By Dan Hogan

Photos by Alisa Machalek

On the Front Page...

Dr. Jeremy M. Berg became director of the National Institute of General Medical Sciences in November, after serving most recently as director of the Institute for Basic Biomedical Sciences and professor and director of the department of biophysics and biophysical chemistry at Johns Hopkins University School of Medicine. The following interview with him took place after his first month on the job.

Continued...

What were your motivations for accepting the offer to become NIGMS director at this point in your career?

On a personal level, it seemed like a whole new set of challenges. Every day there's something new to learn and think about. That's what I hoped would be true, and it's surpassed my expectations.

Second, I'm a strong believer in the importance of basic research. NIGMS has done more than any other organization to foster basic research in biomedical fields. Having a chance to participate in decisions about how to make the institute as effective as possible and figuring out which directions are exciting is what I thought would be fun. And it is.

Dr. Jeremy Berg holds wire model of nucleosome core particle, one of many models he has made.

And the third reason is public service. I feel that if people benefit from the system, they have to give back. There are some significant challenges, though. There are so many things that could be done, you have to pick carefully what you decide to do. And you have to balance the long view of basic research that's relatively untargeted — that is, figuring out fundamental mechanisms of biological processes — with more directed efforts where you know what you want to know.

In addition to serving as director of NIGMS, you'll be continuing your own research here at NIH. Tell us about this part of your work.

My lab will be within the Laboratory of Molecular Biology in the National Institute of Diabetes and Digestive and Kidney Diseases. Both this lab and NIDDK's Laboratory of Chemical Physics have had a strong basic science bent over their entire existence. It seemed like the natural place, and I'm delighted that they were pleased to have me on board.

In terms of research areas, the overarching theme of my research is molecular recognition — that is, how do molecules recognize specific binding partners, where does this specificity come from on a biophysical level, and can you understand those things well enough that you can predict what binds to what or design things for particular targets?

For me, this started off with zinc finger proteins. My training is as an inorganic chemist. But I decided as a postdoc to change direction completely and work on DNA binding proteins. I was trying to figure out how to combine inorganic chemistry and DNA binding proteins at just about the right moment, to within a week of when zinc-containing DNA binding proteins were discovered. And I thought, "Cool." That was in 1985, when that paper got things going.

The other nice thing was that the protein I was studying was from Xenopus — from frogs — which seemed to me to be pretty obscure. So I thought I would have this whole area to myself for a while. And it turned out that these zinc finger motifs are the most abundant motifs encoded in the human genome. There are 700 or 800 zinc finger genes, and literally thousands of zinc finger domains, in the human genome and other eukaryotic genomes. So it's been the tip of a very big iceberg, which has been stimulating in all sorts of ways.

NIH director Dr. Elias Zerhouni recently unveiled the NIH Roadmap for Medical Research. How do you see NIGMS's role in the Roadmap?

The Roadmap is an attempt to find areas that cut across all of NIH and aren't disease-specific, but where techniques or technologies or other sorts of infrastructure are needed to address problems in a broad sense. In a lot of ways, the Roadmap overlaps substantially with the NIGMS mission of supporting fundamental biological processes that are not specific to a particular disease.

NIGMS has clearly been ahead of the curve in several Roadmap areas. For example, NIGMS has been doing more and more interdisciplinary training programs — molecular biophysics, the chemistry-biology interface, and so on. Also, the institute has supported interdisciplinary research teams — through its "glue grants," for example — that are right along the lines of what Dr. Zerhouni was thinking about in the Roadmap.

I think the Roadmap initiatives are very exciting. The science will be good. It will help the image of NIH, in terms of making people realize how much already goes on between institutes. But it will also help the institutes work together better than they ever have.

In what directions would you like to steer NIGMS over the next 5 to 10 years? Are there any research areas in particular that need more support?

A lot of things in the Roadmap or pre-existing programs at NIGMS are pointed in the right direction. But from the broadest perspective, I think the key — although it's getting to be an overused term today — is systems biology. We spent the last few decades effectively looking at all the little pieces that make up biology, from identifying 35,000 or so genes to trying to determine 3-D structures of as many proteins as we can.

But biology takes place in a lot of interacting components — proteins bind to DNA, proteins form simple or complicated complexes where the function is really not the sum of the parts but is much bigger. By working both directions #151; from individual molecules to complexes to macromolecular machines to organelles, on up, as well as from organisms to cells to structures within cells, organelles, and so on — you can start seeing individual molecules inside cells doing things.

Berg uses wire models he constructed to show how a zinc finger protein fits into the major groove of double-helical DNA. He has been fascinated with molecular structures since his youth.

Everything is ripe to meet in the middle. It's sort of like the transcontinental railroad, where the two directions are going to start meeting pretty soon. And you have to make sure that the necessary technologies are being fostered, and that the human resources — the people — are being trained well enough to understand how things work.

If you could write your own job review, how would you like it to read a year from now, or a decade from now?

I guess, "good listener, creative problem-solver." With NIGMS, it's not too different from how I felt when I was working on the fifth edition of Lubert Stryer's Biochemistry textbook. You know, it was so effective at what it does that I didn't want to be known as "the person who ruined Stryer's Biochemistry book." So, likewise, I don't want to be known as "the guy who ruined NIGMS." [laughs]

I've been incredibly impressed with how wise the leadership of NIGMS has been in the past. And the fact that NIGMS is well positioned for the Roadmap initiatives is reflective of that. So, I'd also like my job performance review to read: "Continued in the fine tradition of NIGMS leaders, from Ruth Kirschstein through Marvin Cassman to Judith Greenberg as acting director in the last couple of years."

Ten years from now, hopefully it would read something like: "Charted new directions, integrating basic research and practical applications." To some extent, I think it's a case of "If I knew, I'd be working on it now." There are going to be discoveries that we can't anticipate that will give us ideas about what directions to go.

For a longer version of this interview, visit http://www.nigms.nih.gov/news/features/berg-interview.html.