The discoveries awarded the 2008 Nobel Prize in Chemistry are a shining example of how fundamental research in one area of science can sometimes lead to highly beneficial applications in another. In this case, finding the key to how a marine organism produces light unexpectedly ended-up providing researchers with a powerful array of tools with which to visualize cell biology in action.
The story begins with Osamu Shimomura’s research into the phenomenon of bioluminescence, in which chemical reactions within living organisms give off light. While studying a glowing jellyfish in the early 1960s he isolated a bioluminescent protein that gave off blue light. But the jellyfish glowed green. Further studies revealed that the protein’s blue light was absorbed by a second jellyfish protein, later called green fluorescent protein (GFP), which in turn re-emitted green light. The ability of GFP to process blue light to green (its fluorescence) was found to be integral to its structure, occurring without the need for any accompanying factors.
In 1988, Martin Chalfie heard about GFP for the first time, and realized that its ability for independent fluorescence could perhaps make it an ideal cellular beacon for the model organisms he studied. Using molecular biological techniques, Chalfie succeeded in introducing the gene for GFP into the DNA of the small, almost transparent worm C. elegans. GFP was produced by the cells, giving off its green glow without the need for the addition of any extra components, and without any indication of causing damage to the worms. Subsequent work showed that it was possible to fuse the gene for GFP to genes for other proteins, opening-up a world of possibilities for tracking the localization of specific proteins in living organisms.
The opportunities offered by GFP were immediately obvious to many, as was the desirability of extending the range of available tags. Roger Tsien first studied precisely how GFP’s structure produces the observed green fluorescence, and then used this knowledge to tweak the structure to produce molecules that emit light at slightly different wavelengths, which gave tags of different colours. In time, his group added further fluorescent molecules from other natural sources to the tag collection, which continues to expand. Complex biological networks can now be labelled in an array of different colours, allowing visualization of a multitude of processes previously hidden from view.
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