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NIH Record

Grantees Win 'America's Nobels,' Lasker Awards

By Shannon E. Garnett

Three NIH-supported researchers recently won the 1999 Albert Lasker Award for Basic Medical Research, the nation's most distinguished honor for outstanding contributions to medical research.

Dr. Clay M. Armstrong, a professor in the department of physiology at the University of Pennsylvania School of Medicine, Dr. Bertil Hille, a professor of physiology and biophysics at the University of Washington, and Dr. Roderick MacKinnon, a professor in the laboratory of molecular neurobiology and biophysics at the Rockefeller University, were recognized for their pioneering research on the functional and structural architecture of ion channel proteins. These proteins govern the electrical potential of membranes throughout the body, thereby generating nerve impulses and controlling muscle contraction, cardiac rhythm and hormone secretion.

Dr. Seymour S. Kety

In addition, Dr. Seymour S. Kety, who became the first scientific director of NIMH in 1951, received the Lasker Award for Special Achievement in Medical Science for his lifetime of contributions to neuroscience, including the discovery of methods for measuring cerebral blood flow that led to current brain imaging techniques and his visionary leadership in mental health that ushered psychiatry into the molecular era.

Kety, who currently serves as a senior psychobiologist at McLean Hospital in Belmont, Mass., and professor emeritus of neuroscience in the department of psychiatry at Harvard Medical School, was also recognized for bringing valuable scientific perspective to the etiology of schizophrenia. Through a series of landmark studies of adopted individuals with schizophrenia, Kety established the importance of genetics in causing the disease.

For more than 30 years Armstrong and Hille have sought to understand electrical signals in the nervous system. Electrical signals enable the brain to receive information from nerves throughout the body and allow muscles to contract.

Their work, and that of Mackinnon, is significant because ion channels are the basic components of the body's electrical system. "Ion channels are little holes in the membranes of all cells," says Armstrong. "The channels open and close to either permit or block certain ions from crossing the membrane. Sodium, potassium and chloride channels are among the most important molecules in the electrical signaling system."

Armstrong was recognized for his work in cell membrane excitability, and for elucidating ion channel gating kinetics. He demonstrated that ion channels have gates that control the movement of ions into or out of a cell in response to small changes in voltage across the membrane. His current research focuses on the idea that proteins in solution are key to understanding ion channel gates at a more basic level.

Hille's research proved that channels are independent physical entities in the membrane, each site generating electrical signals that make it possible for cells to talk to one another. In addition, he demonstrated that the channels are sized to accept one kind of ion or another. Their pores have the capacity to act as a molecular sieve. He established that the pores contain water molecules, which also contribute to the ion selectivity.

Currently Hille, who wrote Ionic Channels in Excitable Membranes — a classic text that is considered the scholarly bible of ion channels — is studying the role of ion channels in a variety of cell systems, particularly G-protein signaling and the control of neurotransmitters such as adrenaline, acetylcholine, serotonin and dopamine.

Dr. Roderick MacKinnon

MacKinnon was honored for his elucidation of the structure and function of potassium channels. His work provided the first molecular description of an ion selective channel.

"The high-resolution structure of the potassium channel determined by MacKinnon and his colleagues provides a clear basis for understanding one of the important problems of biology — how ions are selected for transport across membranes. The opportunity now exists for a detailed mechanistic understanding of the way such channels are controlled in normal and aberrant cells," said NIGMS director Dr. Marvin Cassman.

"The work of Armstrong, Hille and MacKinnon is a wonderful extension of work begun 50 years ago by A. Hodgkin, A. Huxley and B. Katz in England. Studies of ion channels have benefited since that time from the work of superb scientists in this country and abroad," said NINDS director Dr. Gerald Fischbach.

The Lasker Awards, often called "America's Nobels," were presented last month at a luncheon in New York City.

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