Biophysicist honored by prestigious Howard Hughes Medical Institute

Released on March 22, 2005
Contact: Laura Gardner 781-736-4204

The Howard Hughes Medical Institute has recognized Brandeis University biophysicist Dorothee Kern as one of the nation's most promising biomedical scientists. Kern's pioneering work in protein dynamics is setting the stage for the development of novel drugs to treat diseases such as cancer, AIDS and Alzheimer's.

HHMI, a leading biomedical research organization, selected Kern, who grew up behind the Iron Curtain in the former East Germany, in a nationwide competition involving about 300 nominated scientists from 200 universities, medical schools and institutes. Of the 11 faculty members in the Brandeis biochemistry department, Kern is the fourth to be named an HHMI investigator, demonstrating the depth of the department's pioneering research and nationally recognized scientific talent.

The funding provides the underpinnings of intellectual freedom and creativity that can translate scientific understanding into medical breakthrough. Kern, along with 42 other scientists, was named an HHMI investigator because she has "demonstrated exceptional promise within four to 10 years of becoming an independent scientist," according to HHMI, which spent $573 million supporting biomedical research last year. "We are committed to providing these scientists...with the freedom and flexibility they need in order to make lasting contributions to mankind," said Thomas R. Cech, HHMI's president.

Kern will continue her research, but won't be under pressure to meet conservative guidelines or specific deadlines. "You need a free mind and a free spirit to do science; creativity is incompatible with pressure," says Kern. "The most fun moments in science are when you get a result you didn't predict or a result you can't explain - that's where discovery comes in."

Discovering how and why enzymes move during the chemical reactions of catalysis is the key to predicting how the thousands of proteins function in our bodies. Ultimately, scientists say, this knowledge will lead the rational design of drugs that can interrupt malfunction or restore normal function without causing other chemical reactions to go awry.

Kern played professional basketball on both the East German and the United German Basketball National Team, for many years as team captain, before coming to the U.S. a decade ago. Just starting as an independent investigator at Brandeis she made a great slam-dunk in the research lab. Kern was the first biophysicist to use nuclear magnetic resonance (NMR) spectroscopy to observe and record the motions of atoms inside proteins during catalysis. NMR is based on the same physical principle as magnetic resonance imaging (MRI), however it allows scientists to "see" proteins in action in unprecedented detail, to atomic resolution, while MRI provides images of whole body parts.

At the time, the field of structural biology was dominated by x-ray crystallography, a technology which can depict the three-dimensional structure of a protein and even a few of its motions during catalysis, but frozen in time, not dynamically.

"I realized early on that showing all these beautiful structures doesn't tell us how these proteins move or function - to learn that I knew we had to move to the fourth dimension." That dimension is the time domain of protein dynamics during catalysis. "It was so surprising that people hadn't done it and I thought of using NMR because I had the knowledge of both physics and enzymology. Scientists told me that my idea of studying enzymes in action was a bit crazy; but if you think it's a cool idea, then you just go for it," says Kern.

The rest is history - in the making. The brilliance of Kern's insight has pushed back the boundaries of knowledge about proteins and their function. Using NMR technology, Kern has been able to show the dynamics of catalysis, as if looking at a film in progress, instead of individual frames stopped in time. The ability to see the dynamic personality of proteins is critical because it is the motions of the molecule that determine its function. Says Kern: "the magic is in the motion."

he implications of Kern's research are breathtaking. The Brandeis scientist was able to characterize the intimate engagement between the human enzyme cyclophilin A and a protein from the HIV virus. This interaction is essential to the virulence of HIV. When the virus is present, it "highjacks" the enzyme within the body, binding to it and enabling HIV to replicate. Kern and others still don't know why cyclophilin is essential to HIV replication, but an understanding of how to disrupt the interaction of the molecule and HIV - without interfering with normal function - would be the first step to developing drugs that might treat or even prevent HIV infection.

Cyclophilin A is just one of the enzymes Kern is researching, along with proteins associated with cancer and Alzheimer's. "The ultimate goal is to understand proteins so well we can predict their structure and movement, and that will help us design drugs that inhibit disease," says Kern.

While Kern's pursuit of stubborn scientific questions takes place on an atomic level in microseconds, using the most advanced technology available, her drive to make discoveries is fueled by simple intellectual hunger: "I can't stop asking how and why - I just want to know all the details, down to what the last atom is doing."

Links

The Boston Globe

submitted by David Nathan