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Highlights in Chemical Biology

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Instant insight: Lighting up biology


04 September 2009

Jellyfish have changed science. Marc Zimmer of Connecticut College, New London, US, explains

Over a period of thirty years Osamu Shimomura caught at least 800 000 jellyfish. Although this feat did not get him into the Guinness World Records, his jellyfish research did earn him a third of 2008's Nobel Prize in Chemistry. The prize was well deserved, for the product of the research has been cited in more than 20 000 publications. Shimomura found that in the jellyfish, Aequorea victoria, a protein called aequorin produces blue light. However, instead of emitting blue light the light is absorbed by green fluorescent protein (GFP) and emitted as green light. 

Jellyfish Aequorea victoria

Fluorescent protein aequorin produces blue light in jellyfish Aequorea victoria

© Credit: Missouri University Extension and Agricultural Information

GFP belongs to a unique class of proteins. Once expressed it folds into a soda-can shape and attacks itself to form the chromophore that is responsible for its green fluorescence. It is this self-propagating characteristic that makes GFP and GFP-like proteins so very useful. No matter which organism or cell type it is expressed in, GFP can form its fluorescent chromophore. 

Applying Shimomura's findings, Martin Chalfie was the first to make use of known promoters - DNA regions that assist gene expression - to express GFP in Escherichia coli and in neurons of Caenorhabditis elegans. That work led to Chalfie being awarded his share of the Nobel Prize. Soon after it was shown that fusion proteins could be created between GFP and proteins whose genes were known, thereby allowing researchers to monitor a fusion protein's production and movement in a living cell. Surprisingly, the proteins still function despite being attached to the 238 amino acid long GFP.

"GFP has developed into a tremendously useful molecule with applications in many areas of science and medicine"
The Nobel triumvirate was completed by Roger Tsien. He was the first to create a wavelength mutant of GFP (a blue fluorescent protein); the first to use fluorescence energy transfer (FRET) measurements between fluorescent proteins; and the first to find an enhanced mutant of GFP (EGFP) and to crystallise it. In 2004 Tsien also produced the mFruits, a palette of new fluorescent proteins, and created a series of genetically encoded FRET sensors to detect calcium, protease, phosphorylation and cAMP (cyclic adenosine monophosphate - a signalling molecule used in many biological processes).

The Nobel Prize cannot be shared by more than three people and they all have to be living at the time the prize is awarded. This invariably means that some very worthy researchers will miss a share in the Nobel glory. William McElroy, Douglas Prasher and Sergey Lukyanov were also influential in making fluorescent proteins one of the most useful tools in biotechnology. William McElroy and his wife, Marlene DeLuca, laid the early groundwork for 2008's Nobelists. They studied firefly bioluminescence and exploited the insect's luciferase enzyme in monitoring gene activity. Both had died by the time the Nobel Prize was awarded. Doug Prasher first conceived the idea of using GFP as a genetic tracer and cloned the GFP gene; however, he was unable to express a chromophore-forming version of GFP. In 1999, Sergey Lukyanov was the first to find a red fluorescent GFP-like protein, which led to the discovery of GFP-like proteins in more than 120 different species.

GFP has developed into a tremendously useful molecule with applications in many areas of science and medicine. It is a molecular microscope that allows scientists to follow in vivo processes that were hidden before the advent of GFP-based techniques. These methods include the cell cycle indicator FUCCI (fluorescent, ubiquitination-based cell cycle indicator); Brainbow, which allows researchers to follow individual neurons in the neuronal spaghetti that is the brain; and the optical highlighters that have resulted in super resolution microscopy techniques. Fluorescent proteins have become routine in many laboratories, and like optical microscopes and spectroscopic methods, descriptions of their use are now relegated to the experimental section of publications. 

"These futurist applications and the beautiful images that fluorescent proteins can trigger create an excellent opportunity for scientists to inform the public about new advances in cloning, stem cell technology and creating genetically modified organisms, and to initiate a debate about the responsible use of these techniques."
Yet in some cases fluorescent proteins can propel scientific publications into the public arena. It is not surprising that news of Ruppy, the ruby fluorescent cloned beagles, circulated the globe earlier this year. So too did reports of the marmoset monkeys that pass GFP expressing ability onto their offspring. These futurist applications and the beautiful images that fluorescent proteins can trigger create an excellent opportunity for scientists to inform the public about new advances in cloning, stem cell technology and creating genetically modified organisms, and to initiate a debate about the responsible use of these techniques.

Read more in the highlight 'GFP: From jellyfish to the Nobel Prize and beyond' in Chemical Society Reviews.

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Link to journal article

GFP: from jellyfish to the Nobel prize and beyond
Marc Zimmer, Chem. Soc. Rev., 2009, 38, 2823
DOI: 10.1039/b904023d

Related Links

Link icon Green Fluorescent Protein website
Green Fluorescent Protein website

Link icon Nobel Prize Website
Nobel Prize Website


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