2008 Nobel Prize in Chemistry to GFP

8 10 2008

This morning, the Nobel committee recognized the work of Osamu Shimomura, Martin Chalfie and Roger Tsien “for the discovery and development of the green fluorescent protein, GFP” by awarding them the Nobel Prize in Chemistry for 2008.  A video of a great lecture on fluorescent proteins by Roger Tsien is available here.

Green Fluorescent Protein

Green Fluorescent Protein

Shimomura first discovered GFP during the study of the bioluminescent protein aequorin, the mechanism by which certain jellyfish glow.  In the footnote to his seminal paper on aequorin purification, he noted the additional presence of “a protein giving solutions that look slightly greenish in sunlight through only yellowish under tungsten lights, and exhibiting a very bright, greenish fluorescence in the ultraviolet of a Mineralite, has also been isolated from squeezates.” 

Aequorea Victoria

Aequorea Victoria

Chalfie took the cDNA of GFP and first expressed it bacteria and worms.  He demonstrated GFP could be used as a molecular tag. Surprisingly, the protein folded and functioned without the use of co-factors specific to the jellyfish.

Tsien developed GFP into the many useful variants we use today.  He reported the S65T point mutation that greatly improved its fluorescent characteristics. His lab also evolved GFP into many other color variants, and demonstrated that these variants could be used as genetically-encoded intracellular sensors for calcium, enzyme action, and glutamate.

Chromophore of the S65T mutant of GFP

The odd man out in this triumvirate is Douglas Prasher.  With a tiny lab and budget, Prasher discovered the primary sequence of GFP and cloned the cDNA of GFP. Unfortunately, around the time of his work’s publication, his grant ran out. Prasher sent out DNA samples to Chalfie, Tsien and others, shut down his lab and left science. Prasher’s contribution was the essential foundation for the explosion of developments in the field.

Some argue that Tsien would have already won the Nobel prize for calcium signaling if not for his contribution to GFP. As a graduate student, he invented the high affinity calcium chelator BAPTA. Using BAPTA as a foundation, he created a large family of fast, bright calcium dyes, including fura-2.  Nearly every fluorescent dye for calcium was either his invention or a close variant of one of these. The importance of these tools for understanding intracellular communication cannot be overstated.

Transgenic GFP mouse


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8 responses

8 10 2008
2008 Nobel Prize in Chemistry goes to the GFP | En.dogeno.us

[…] 2008 Nobel Prize in Chemistry to GFP from Brain Windows […]

1 11 2008
28 11 2008
Graham Ellis-Davies

Andrew, did Roger make BAPTA and quin2 and a PhD student or as a postdoc?

28 11 2008
andrewhires

BAPTA was his Ph.D. thesis. He likes to tell the story that he had 3 failed projects and BAPTA was his last chance project that only had a few weeks to make it work before he’d have to give up…

Quin-2 was in the same paper. But I’m not sure the exact timing relative to post-doc beginning.

29 11 2008
Graham Ellis-Davies

Andrew
thanks for the historical info, and check out footnote 2 in JBC (1985) 260:3440 for dye nomenclature😉

30 11 2008
andrewhires

Thanks G.

By far the best review of the history of calcium dyes I have read is this book chapter.
Tsien, R.Y. 1999. Monitoring Cell Calcium. In Calcium as a Cellular Regulator, ed. by E. Carafoli and C. Klee. New York: Oxford University Press, pp. 28-54.

Can’t find it on pubmed, but it’s hosted on the Tsien Lab website.

22 03 2010
austin

that is cool

26 01 2013
Gui Blame

where can i buy one of these rats?

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