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In the cold ocean current off the San Juan Islands, a graceful Pacific
Northwest jellyfish, Aequorea victoria, hypnotically undulates like a
shaggy parasol, softly emitting a green, other-worldly glow. The cause of the
glow--green fluorescent portein, or GFP--is the only known spontaneously
fluorescent protein in all of nature. In the past five years, thousands of
biomedical researchers around the world have begun using this exotic jellyfish
protein (now cultured in bacteria) as a tiny lantern illuminating important
biological processes previously hidden from view. Groundbreaking work to expand
dramatically the usefulness of this remarkable protein is taking place at the
University of Oregon in the lab of molecular biologist
Jim Remington.
"This unique characteristic of GFP makes it extremely useful for biomedical
researchers," says Remington, an associate professor of
physics. "It gives them
a window through which to peer at the inner workings of any type of living
cell."
For example, by using genetic engineering techniques researchers can splice
GFP onto other proteins of interest--say, a therapeutic hormone--so that where
the hormone goes, the GFP goes. Shining a certain kind of light on the cell
causes the GFP to glow and allows a scientist to see where the hormone lodges
and where it has the most potent effect. Similarly, a researcher studying a
particular gene can replace part of that gene with GFP so that when the gene
"turns on" the GFP also lights up.
"Scientists were finding new uses and even more interesting properties of the
protein on nearly a daily basis," Remington asserts. "But curiously, no one
knew exactly how the GFP worked--they didn't know how it hung together."
An expert in cracking the molecular codes of complex proteins, Remington
decided to decipher the enigmatic molecule. In a concentrated nine-month
effort, he and two fellow UO researchers determined GFP's structure. They
discovered the elegant assemblage is composed of 238 amino acids arranged in a
stable birdcage-shaped structure with a small glowing strand of matter
suspended within like an incandescent parakeet on a perch.
"Now that we know the structure, we can begin modifying it for additional
uses," Remington says. His research team has already changed one of GFP's 238
amino acids to create a protein with a yellow glow; now they are working on a
blue-green variant. Other labs have created blue- and red-glowing versions of
GFP.
What use are these differently glowing GFPs?
"By itself, GFP provides a simple on-off test," Remington explains. "But
researchers could use a variety of colored GFPs to test for a number of
different possibilities at one time. This makes it a much more useful tool."
Remington's team is working on one version of the protein that responds to
changes in pH--the chemical scale of alkalinity and acidity--that are
associated with a wide range of cellular activities.
Another modified version under study signals changes in calcium
concentration. Calcium levels fluctuate just before a nerve cell fires, so an
indicator of when this takes place could be very useful in research into nerve
tissue regeneration.
Remington also notes that since GFP fluorescence can be turned on and off with
light, it is easy to envision using it as a bio-optical data storage device. A
CD-sized storage disc, Remington calculates, could potentially hold ten
thousand times the data of one of today's CD-ROMs.
"This protein is a key," he says. "It is already unlocking many doors, and it
promises to unlock others that we've been well aware of but have been unable to
open."
