7.15 2008 Chemistry Nobel Prize goes to those who lit up cells

http://arstechnica.com/news.ars/post/20081008-2008-chemistry-nobel-prize-goes-those-who-lit-up-cells.html

By John Timmer | Published: October 08, 2008 - 04:47PM CT

Many of the techniques that biologists use for looking at cells and organisms involve taking the equivalent of a static snapshot of the state of these systems. But life isn't a photo; it's a movie, dynamic and changing. This year's chemistry Nobel Prize goes to a trio of researchers that found and developed an obscure protein from a jellyfish and developed it into a system that has given us an unprecedented view of the movie of life.

The protein has a name, Green Fluorescent Protein (GFP), that tells you everything significant about it. Lots of organisms have some sort of bioluminescent capacity, but most of these tend to involve several proteins and/or additional chemicals. The firefly protein, luciferase, is an example of this: it glows, but only if provided with a very specific chemical, which gets used up in the process.

GFP is different. Once a cell produces it, some of the amino acids that make up the core of the protein undergo a series of spontaneous reactions that require only oxygen. This ultimately produces a structure in the protein that can absorb ultraviolet light and emit a bright shade of green in response. Because only oxygen is required for this reaction, any cell that can produce GFP, from bacteria to humans, can potentially glow green. Because no extra processing is needed, even living cells can be imaged using GFP.

GFP expressed in nerve cells lights up the
axons they extend from the developing
spinal cord. Credit: me.

The prize recognizes three key steps in the development of GFP as a biological tool. One of the three Laureates, Osamu Shimomura of Woods Hole's Marine Biological Lab, is cited for his isolation and basic characterization of the protein. Shimomura's careful characterization of the chemistry of the protein ultimately allowed other researchers to clone the gene that encoded the protein. Both Shimomura and the cloners, however, never looked into the origin of its fluorescent properties; a paper describing the gene contains the quote, "It is very unlikely that the chromophore forms spontaneously."

The second Laureate, Columbia University's Marty Chalfie, gets credit for that. When not distracted by teaching this author undergrad genetics, Chalfie obtained a copy of the DNA encoding the gene and found that it happily glowed green when expressed in bacteria, even though these cells lacked the jellyfish enzymes and chemicals that were still thought to be needed. Correctly recognizing that the protein could glow on its own, Chalfie expressed it in his experimental organism of choice, the transparent roundworm C. elegans. The worms also glowed, and soon Chalfie was imaging individual cells as the organisms developed.

The original GFP wasn't perfect, however, as it had a tendency to lose its ability to glow, and, for technical reasons, green isn't the most convenient color. Roger Tsien of UCSD received a Nobel for the various improvements he made to GFP. By making various mutations in the gene, he improved its stability and altered the wavelength of the light it emits, creating Cyan-FP and Yellow-FP variants, among others. Tsien has also looked further afield, developing Red-FPs based on a protein isolated from corals.

In the mean time, the various FPs have changed the way we look at cells. Hook them up to DNA sequences that cause the gene to be expressed in specific cells, and those cells glow, allowing their development to be tracked in real time in everything from worms to mice. Fuse GFP to a protein that binds to DNA, and the chromosomes can be tracked as cells duplicate their DNA and divide. Individual cells, proteins, parts of cells—basically, any place you can attach or ship GFP to—can be imaged in living cells and organisms.

For their part in making life into a movie, these scientists are taking home a well-deserved Nobel Prize.

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