Saturday 11 October 2008

GFP is awesome, and the Nobel committee agrees

First isolated and purified in the 1960s and 1970 green fluorescent protein (GFP) has become a remarkable tool in the understanding of cellular biology and gene expression. It's found in glowing jellyfish, notably Aequorea victoria. The energy for their glow actually comes from an interaction between another protein, aequorin and calcium ions, Ca2+. Binding to calcium pushes aequorin into an excited configuration which relaxes by giving off a photon of blue light. That's bioluminescence. Fireflies do it too and many deep sea fish and plankton, each in their own way.

Now here's the interesting bit, GFP absorbs the blue light from aequorin and re-emits it as green light. It fluoresces; shine a blue light on GFP, it glows green.

In 1992 the gene for GFP was cloned by Douglas Prasher and a new branch of science took off. Get the gene for GFP into about the right place and it will be expressed alongside a normal gene. Then by shining a blue light you have a measure for that gene's activity, observe the green glow. Get the GFP gene into exactly the right place and you can tag a protein with a fluorescent marker, and then follow it's movements by its glow.


As an example I was going to include a video of the nematode Caenorhabditis elegans* expressing GFP in it's nervous system, but the poster at YouTube won't let me! Come on, it's 11 seconds long man, get real... anyway you'll have to click this link.

In the main, I was surprised by the lack of GFP videos on YouTube. GFP is cool, get posting your work guys...

Among the few is another video of C. elegans, this time there are two of them and they are very young. I don't know what protein they are expressing but watch it dissipate and re-group during cell division.


Of course technology and understanding move on over the years. Now it is not just green fluorescent protein but a spectrum of colour.

Here's the Brainbow mouse -->



As Roger Tsien wrote in 1998**

In just three years, the green fluorescent protein (GFP) from the jellyfish Aequorea victoria has vaulted from obscurity to become one of the most widely studied and exploited proteins in biochemistry and cell biology. Its amazing ability to generate a highly visible, efficiently emitting internal fluorophore is both intrinsically fascinating and tremendously valuable. High-resolution crystal structures of GFP offer unprecedented opportunities to understand and manipulate the relation between protein structure and spectroscopic function. GFP has become well established as a marker of gene expression and protein targeting in intact cells and organisms. Mutagenesis and engineering of GFP into chimeric proteins are opening new vistas in physiological indicators, biosensors, and photochemical memories.
Martin Chalfie, Osamu Shimomura and Roger Y. Tsien share the 2008 Nobel Prize in Chemistry for their discovery and development of the green fluorescent protein***.
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*I can't pronounce it either. Say C. elegans and it's OK.
**Tsien RY. Annu Rev Biochem. 1998; 67:509-44.
***And why not Douglas Prasher?

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