Hold for NATURE
Embargo: JULY 24, 1997
Media Contact: Warren R. Froelich, (619) 534-8564, [email protected]
GLOW OF JELLYFISH MAY LIGHT WAY TOWARD NEW OPTICAL STORAGE DEVICE
Like a searchlight that, with the flip of a switch, illuminates a path in the dark, a team of researchers at the University of California, San Diego has found a way of controlling a tailor-made version of a protein that gives the glow to the Pacific Northwest jellyfish.
The discovery, described in the current issue of the British journal Nature, not only sheds light on the inner workings of the green fluorescent protein (GFP) of the jellyfish Aequorea victoria, it also suggests a potential new way for one day storing and accessing computer memories in packages the size of a single molecule.
"It's a radical proposal to think of doing optical storage in a single individual molecule," said W.E. Moerner, professor of chemistry and biochemistry at UCSD. "What we've discovered is the nucleus, the essential element, for this type of optical storage device."
The research could have more immediate use for biological markers. By linking GFP genes to those encoding other proteins, and then switching them on at precise moments, molecular biologists should be able to track when and where those genes are expressed inside living cells and tissues.
"Essentially, you'll be able to follow a protein around a cell and see whatever it is doing, whether it's an antibody attaching to an antigen, or a protein exchanging messages with another protein," said Robert M. Dickson, a postdoctoral researcher in Moerner's laboratory.
Briefly, the UCSD researchers describe a unique switching mechanism, based on alternating wavelengths of light, which brings out the glow in a single molecule of a GFP mutant. Initially, the molecule is excited by a green laser beam with a wavelength of 488 nanometers. After releasing its energy in the form of yellow light particles for a while, the molecule subsequently darkens, only to be re-awakened with the help of a mercury lamp (which irradiates at a blue wavelength of 405 nanometers). The process was repeated several times, with the same results.
"Presumably, the glow will turn off, or bleach out permanently, at some time," said Dickson. "However, we have not investigated how long that would take."
Theoretically, by alternating the wavelengths of the external light source, information could one day be read or written to a single GFP molecule, or bit. In computer parlance, data is stored in a series of bits--1's and 0's--which now are written on the magnetic surface of tape or disks as a pattern of alternating magnetic orientations. With this biomolecular approach, for example, a single glowing molecule could correspond to a bit value of 1, while a single darkened molecule might suggest a bit value of 0.
"If you can address each individual molecule, then you can store a lot more data in a smaller data storage device," said Dickson. "You get much more storage bang for your buck."
Currently, a light-sensitive protein made by saltwater bacteria called bacteriorhodopsin is the only other protein being investigated as the basis for a new generation of optical storage devices. Researchers appreciate bacteriorhodopsin's potential because it exists in two stable forms, one purple and the other yellow. Shining two lasers of different wavelengths alternately on the protein flips it back and forth between the two colors.
"However, bacteriorhodopsin cannot be addressable as a single molecule," said Dickson. "With GFP we can exploit the power of a single molecule for this purpose."
The ability to harness the glow of GFP for optical storage devices and other potential applications stems, in part, from research by Roger Tsien, a UCSD professor of pharmacology, chemistry and biochemistry, and an investigator with the Howard Hughes Medical Institute.
Last year, Tsien and other scientists took the first look at the three-dimensional structure of a GFP molecule and a mutant form of the protein; each bore a likeness to a covered barrel housing a glow-producing dye, or fluorophore.
By helping to explain the properties of the fluorescent protein, the 3D map provides a guide for modifying it. In the normal protein, the green glow comes from a structure formed by three amino acids--serine-65, tyrosine-66, and glycine-67.
Knowledge of the three-dimensional structure of the protein means researchers not only can change the fluorophore, they can also alter the amino acids that come into contact with it. For example, Tsien and Andrew B. Cubitt, a researcher with Aurora Biosciences in La Jolla, Calif., replaced tyrosine-203--which resides near the light-producing fluorophore--with phenylalanine or tyrosine. Tsien and Cubitt gave the resulting mutants, which radiate a more yellowish color than any of the previous types of GFP, to Dickson and Moerner, who trapped the proteins inside a porous gel whose matrix is bathed in water at room temperature. This gel, called polyacrylamide or PAA, was recently found by Moerner and Dickson to be an ideal substance for confining molecules in surroundings that mimic their natural environment.
"The fact that we can detect the glow from single GFP molecules at room temperature is significant since the only other molecular switches that rely on a single molecule require very low temperatures, liquid helium temperatures, of about 2 degrees K.," said Moerner. "For routine applications, that type of environment would not be practical."
Although the researchers discovered how to repeatedly switch on the protein's glow after it had darkened, they also noticed that the protein would periodically light up and darken on its own, a phenomenon called "blinking."
Before mutant GFPs could be made available for practical optical storage, the researchers say they must reduce or eliminate these blinking episodes.
"Presumably, through biochemical techniques, one could engineer out this blinking state, so you're left only with switching, where the molecule is turned off and then turned on through external excitations," said Dickson.
Indeed, one of the advantages of working with a protein is the ability to genetically alter its structure, and its immediate surroundings, to create new and improved versions.
"You can do mutations and then screen them for this optical switching feature," said Dickson.
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