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February 7, 2001For immediate release:

MOLECULAR STUDY AMES FOR CLUES TO RETINA DECLINE

ROCKVILLE, Md.-A molecular study that could lead to a remedy for poor eyesight caused by a degenerating retina is the focus of a new $200,000 grant from the Arnold and Mabel Beckman Foundation.

James B. Ames, research scientist at the University of Maryland Biotechnology Institute (UMBI), has received the foundation's Young Investigator Award Grant to support his work in determining the three-dimensional molecular structure of key signaling proteins in the retina at UMBI's Center for Advanced Research in Biotechnology (CARB). The three-year grant will enable Ames, a molecular biologist, to simulate in the laboratory how such retinal proteins sometimes malfunction. The most common cause of degenerating retinas is defective genes that code for the signaling proteins. "In the retina, rod-shaped cells act as exquisitely sensitive light detectors that depend on a critical balance of the element calcium," explains Ames. He has learned the molecular structure of a protein called recoverin that helps keep calcium levels in balance in both retinal rod and cone cells, as they accept light streaming through the iris.

"It is very expensive to determine the structure of an eye protein," Ames comments. "In recoverin there are about 10,000 atoms. We used NMR spectroscopy to measure the distances between the atoms, one by one, to determine their three-dimensional spacing. Once we know the shape, we can study how the proteins attach to the surface of the rod cell membranes."

To clarify how the proteins interact with the cell membranes, Ames will next experiment with artificial rod cell membranes--a necessary step before medical researchers can design new drugs to correct defects in the signaling protein systems. Says Ames, "We want to see how these proteins attach to a two-dimensional surface--a snapshot of the protein structure docking to a rod membrane."

So far, Ames has learned that a fatty acid molecule, wedged deep inside the core of the much larger recoverin molecule, seems to be a hands-on manager of calcium in the retinal cells. When calcium binds to recoverin, the fatty acid is thrust out. "I originally picked recoverin to study because I was intrigued to find out how the attached fatty acid works in concert with the calcium binding sites to guide the protein to membrane-bound targets," he reports.

New technology at CARB allows researchers to piece together molecular puzzle parts of the signaling proteins to learn how light generates a signal, how the system is excited, and how each light excitation is regulated against a constant background of light stimuli into the eyes. Light energy as low as a single photon will trigger a nerve impulse that is then translated and processed in the brain.

The Beckman Foundation was established in September 1977 to support basic scientific research, primarily in the fields of chemistry, biochemistry and medicine. The mission of the foundation is to support leading edge research and particularly to foster the invention of methods, instruments and materials that open up new avenues of research and applications.

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