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Roderick MacKinnon in his lab.

 

Roderick MacKinnon, a Professor of Molecular Neurobiology and Biophysics at the Rockefeller University, was attracted to scientific inquiry from his earliest years. As one of seven children growing up in Burlington, Mass., outside Boston, he distinguished himself from his siblings and friends by his love of solving puzzles.

This trait persists to this day and has driven him to tackle some of the thorniest problems of neurobiology. Last year, MacKinnon was praised by colleagues when he solved the molecular structure of the potassium ion channel--an accomplishment hailed by Science magazine as one of its "Breakthroughs of the Year," and described in a commentary by a fellow scientist as "a remarkable achievement."

MacKinnon is acclaimed in his field for his penetrating ability to make sense of technical information and bring it to a clear resolution in his mind. "I've always been better at analysis than memorization," he says. He has always had a fascination observing the intricacies of the natural world. He recalls as a boy wanting to go to summer school because students were allowed to take home their own microscope--an instrument MacKinnon eagerly put to use studying grass, leaves and insects. "I loved watching the tiniest things swim and move," he says.

His interest in science did not waver as he grew older, and he benefited from parents who did not attempt to steer him toward any particular occupation.

"I was never pressured into science or any other particular field by my parents," he says. "All they expected was that we attend college and then make the career decisions ourselves."

MacKinnon decided to attend nearby Brandeis University and majored in biochemistry, receiving a B.A. in 1978. He moved on to study medicine at Tufts University, securing his M.D. in 1982, and did a residency at Beth Israel Hospital at Harvard Medical School.

In 1986, however, he abandoned his plans to practice medicine in order to pursue postdoctoral studies back at Brandeis in the laboratory of his undergraduate mentor Christopher Miller. "My scientific career in effect began at the age of 30," he says. "My wife was very understanding and supportive of my decision, given that it meant additional years as a student rather than the financial stability a medical practice would offer."

MacKinnon also is very grateful to Miller for taking him under his wing and helping him develop a fuller understanding in physics and chemistry. "Chris Miller exemplified the spirit of science and the approach to figuring out answers to very difficult questions," he says. "That is what attracted me to his laboratory and has guided my scientific career."

Under Miller, MacKinnon began working on the biophysical aspects of ion channel function. Shaped like tiny doughnuts floating in oil, ion channels perform the dual functions of gateway and gatekeeper. The holes in the doughnut form the gateway through which the ions flow. However, these holes, or pores, are endowed with special properties that enable different channel proteins to be selective as to which ions they allow passage.

In Miller's lab and then in his own laboratory at Harvard Medical School, MacKinnon sought to understand the structure of the protein and the answers to two compelling questions: What do these channels look like? And how are they able to allow passage of potassium ions while blocking other ions that are similar?

Using electrophysiological and biochemical approaches at Harvard, MacKinnon studied the interaction of the potassium channel with a specific toxin derived from scorpion venom and figured out that the toxin blocked the flow of ions by sitting directly on the pore of the channel. He then exploited the toxin to analyze the subunit structure, the moving gates and the ion conduction pathway of potassium channels.

Upon realizing he needed a better understanding of structural biology, MacKinnon moved to Rockefeller University in 1996 as a professor and head of the Laboratory of Molecular Neurobiology and Biophysics. Despite the expertise and insight he had gained at Brandeis and Harvard, solving the channel structure was a daunting task-too daunting, in the minds of some people.

"When I was at Harvard, friends and colleagues were telling me it would take 10 years to figure out the ion channel structure, but I was determined to try," MacKinnon says. "Rockefeller said to me, in essence, that they like scientists who take risks and they were willing to take me on in that attempt. It is nice when an institution can offer that kind of support. In addition, it has been tremendously helpful to my research to be able to confer with the experts at Rockefeller in related fields."

At Rockefeller, MacKinnon learned X-ray crystallography, a skill he realized he would need in order to directly visualize a potassium channel in a way that previous experiments could not accomplish. This newly acquired proficiency led to the first structure of the potassium channel, which was published in Science in April 1998.

Many questions remain unanswered. MacKinnon suspects that ions in the pore interact with one another through the structure of the protein, but establishing this will require higher-resolution data. The ability to actually look at ion channel structures has already begun to stimulate new directions in ion channel research. His laboratory recently solved the structure of the channel's Beta subunit, which regulates when the channel opens and closes.

These new discoveries keep him fascinated and looking forward to what lies ahead in the field he so enjoys. The occupation that he finds so rewarding has recognized MacKinnon's contributions and bestowed upon him some of its highest honors: MacKinnon is a member of Alpha Omega Alpha Medical Honors Society, a PEW scholar in the Biomedical Sciences and the recipient of the Mcknight Scholars Award, the Biophysical Society Young Investigator Award, the Mcknight Investigator Award, the W. Alden Spencer Award and the AAAS Newcomb Cleveland Prize.

"My belief is that if you do good science, science will take care of you," he says. "If you tackle a problem and keep working on it, eventually you will find some kind of outcome.

 

 
 

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