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James Berger on Tiny Protein Machines

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James Berger on Tiny Protein Machines

By Catherine Kolf

James Berger on Tiny Protein Machines

James Berger is a professor of biophysics and biophysical chemistry and of oncology. His lab studies biological nanomachines — proteins that carry out mechanical tasks. 

How did you become interested in science?

BERGER: I grew up in the Santa Fe area, and both of my parents worked at Los Alamos National Laboratory, the nuclear research facility. My first taste of research came in high school, when my AP biology teacher helped me get a summer internship in a lab at Los Alamos. I studied how certain plants break down toxic organic compounds like TNT and survive in soils with high concentrations of toxic metals like cadmium. I was hooked! That love for research is still what keeps me going.

You just left a full professorship at the University of California, Berkeley to come here a year ago. California is not often a state people like to leave. What made you come here?

BERGER: My wife’s family lives in this area, and we wanted our kids to be able to visit with their grandparents and cousins more. Plus, we both liked the career opportunities here. She’s a professor of art history and Near Eastern studies at Homewood. It’s nice to be on the East Coast, where there are so many great museums. And I actually enjoy the warm summer evenings here. I could do without the mosquitoes, but the fireflies make up for them!

What does your lab study?

BERGER: We study biological nanomachines: proteins that carry out mechanical tasks by moving various parts together in a concerted and coordinated manner. For example, one of the enzymes we study forms a six-membered ring that spins like a rotary engine to pull RNA through the center of the complex.

Like any motor, these nanomachines need fuel. A very common fuel is the molecule ATP. When you digest your food, it’s broken down into sugars and other energy-storing molecules that are then turned into ATP. The little protein motors can use the chemical energy in ATP to do mechanical tasks, the same way a car uses the energy in gas to turn its gears and go. We try to understand how the proteins use ATP and what their functions are.

The shape of a protein determines its function. We try to figure out the shape of these proteins, where each atom is and how they work together. It's like looking at the engine of a car with X-ray vision. You'd see the shape of the parts and where they are located, and then you'd guess what the function of each part was. You could then confirm or refute your guess with a few tests, like pulling out a part and seeing what happens to the activity of the motor.

Why do these proteins capture your imagination?

BERGER: There are about 2 meters of DNA in every cell of our bodies, but the cells are only 2 to 10 millionths of a meter wide! Stuffing all of that DNA into a cell is akin to stuffing holiday lights into a box without winding them first—they don’t fit well, and they tangle easily. How does the body do it? It turns out that there are proteins that loop, twist and compact DNA to fit it neatly into cells. But solving that problem introduces another one: When the DNA needs to be read, how do the reading proteins get at it now that it’s so tightly coiled? How do they open the double strands without the DNA getting coiled and twisting up on itself like a telephone cord? I think this balancing act is just fascinating.

1976 Triumph TR6 A 1976 Triumph TR6

What do you say to students interested in the sciences?

BERGER: I don’t think, as some do, that we are training too many graduate students. There has never been a better time to do science. The tools that are available now allow us to ask questions we could never ask before. It is truly exciting, and there are innumerable opportunities for post-Ph.D. individuals within and outside of science. In addition to needing research scientists to continue to drive discovery, we also desperately need science-educated lawyers, politicians and entrepreneurs to drive public policy and the economy forward.

Do you have any hobbies outside of science?

BERGER: My kids keep me pretty busy, but I do have an old British roadster, a 1976 Triumph TR6, that I’ve been working on restoring little by little since high school!