Los Angeles Times, October 09, 2008

Three U.S.-based scientists share Nobel chemistry prize

Roger Y. Tsien of UC San Diego, Martin Chalfie of Columbia University and researcher Osamu Shimomura developed a fluorescent jellyfish protein that allows researchers to trace cell molecules.

By Thomas H. Maugh

Three U.S.-based scientists will share the 2008 Nobel Prize in chemistry for their development of a green fluorescent protein from jellyfish that has provided researchers their first new window into the workings of the cell since the development of the microscope.
Roger Y. Tsien, 56, of UC San Diego, Martin Chalfie, 61, of Columbia University, and Osamu Shimomura, 80, a Japanese-born researcher who works at the Marine Biological Laboratory in Woods Hole, Mass., will share the $1.4-million prize for developing the protein that the Nobel committee called "a guiding star for biochemists, biologists, medical scientists and other researchers."
The protein can be attached to any of the 10,000 individual molecules within a living cell, allowing researchers for the first time to trace the paths of the molecules as they wind through the complex pathways of life.
In a hastily arranged news conference Wednesday morning, Chalfie said he had slept through early morning phone calls from Sweden and did not know about the prize until he woke up and checked his laptop to see who had won.
"It's not something out of the blue, but you never know when it's going to come or if it's going to come, so it's always a big surprise when it actually happens," he said.
In a telephone news conference, Tsien said he too was surprised. "There had been some rumors, but from sources whose reliability was questionable," he said.
The story starts with Shimomura, whose education was disrupted by World War II. In 1953, he was hired as an assistant in the Nagoya University laboratory of biologist Yashimasa Hirata, who assigned him to discover what made the remains of a crushed mollusk glow when it was moistened with sea water.
The project was considered so difficult that Hirata had not wanted to give it to a student who would need to succeed to obtain his degree. Nonetheless, within three years, Shimomura had isolated the protein. When Shimomura was recruited to join Frank Johnson at Princeton University, Hirata arranged for Nagoya to award him his doctorate, even though he was not enrolled as a student.
In the summer of 1961, Shimomura and Johnson began collecting bioluminescent jellyfish in Friday Harbor in the San Juan Islands of Washington State, returning to Princeton with extracts from 10,000 of them.
In 1988, Chalfie heard about GFP and thought it would be useful for tracing the fate of proteins in the roundworm, Caenorhabditis elegans, which is widely used in biological studies because it is transparent, allowing researchers to study its organs under a microscope.
When Douglas Prasher of the Woods Hole Oceanographic Institution isolated the gene for GFP, Chalfie assigned graduate student Ghia Euskirchen to insert the gene into the bacterium Escherichia coli. Within a month, she had produced a bacterium that glowed green.
Next, Chalfie attached the gene to receptors in C. elegans that are involved in the sensation of touch. The cover of the journal Science in February 1994 showed a picture of the organism with the touch neurons glowing bright green.
Tsien, meanwhile, studied how the color-producing part of GFP works and devised ways to alter its gene to produce variants that glowed cyan, blue and yellow. Eventually, he and other researchers produced a family of proteins that glowed in a whole spectrum of colors, allowing researchers to follow the path of several different proteins simultaneously.
One memorable experiment tagged mouse brain proteins yellow, cyan and red, producing a mouse whose brain glowed in the colors of a rainbow -- a "brainbow," as it was tagged.
Researchers have subsequently adapted the technology so that microorganisms will glow in the presence of heavy metals, explosives such as TNT and other chemicals, allowing the mircoorganisms to be uses as sensors to find the materials in the environment.
GFP is now used in some toys and even in art. In 2000, Chicago artist Eduardo Kac commissioned the creation of a green-glowing bunny named Alba.
But there still remains one major mystery, according to the Nobel committee. No one knows yet why the jellyfish glows in the first place.

thomas.maugh@latimes.com

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