Glowing proteins lead the way to the Chemistry Nobel Prize

The 2008 Nobel Prize for Chemistry has been awarded equally to three chemists "for the discovery and development of the green fluorescent protein (GFP),” one of the most important tools in bioscience.

This year’s prize winners are Professor Osamu Shimomura of the Marine Biological Laboratory, in Massachusetts US, Professor Martin Chalfie of Columbia University, New York, US and Professor Roger Y. Tsien of the University of California, California US.

GFP and related proteins can be tagged to proteins of interest and used to monitor the biochemical processes occurring within living cells and organisms using various fluorescence microscopy techniques.

Phenomena such as gene expression, protein localisation, protein-protein interactions, cell division, chromosome replication and intracellular transport pathways have all been studied using GFP tagging experiments and dramatically increased our understanding of the molecular mechanisms occurring in biological systems.

Prof. Shimomura first isolated GFP in 1962 from the jellyfish Aequorea victoria whose outer edge glows green when the jellyfish is agitated.

It was isolated along with the bioluminescent protein aequorin that reacts with calcium ions and releases blue light.

When the Aequorea victoria is agitated it releases calcium ions which react with the aequorin to release a blue flash of light which excites the GFP and causes it to fluoresce.

Prof. Chalfie first heard about GFP during a seminar in 1988 and realised it would be a fantastic tool for mapping organism if only it could be connected to the various proteins in the cell.

After one of Prof. Chalfie’s graduate students managed to get Escherichia coli (E. coli) bacteria to produce GFP, the team placed the GFP-expressing gene behind a promoter that is active in six touch receptor neurons in the roundworm Caenorhabditis elegans (C. elegans) so that the neurons could be seen under UV light.

This technique was then used by various researchers to study a myriad of other systems and processes.

Prof. Tsien charted the chemical structure of the GFP chromophore unit and showed that three of the protein’s amino acids react with each other to form the chromophore in the presence of oxygen.

He then modified GFP-encoding gene to produce various GFP mutations that absorb and emit light at different wavelengths.

While he created GFP mutants that emit various colours such as cyan, blue and yellow he struggled to produce a red GFP mutant unit.

However, two Russian researchers discovered a fluorescent red protein DsRED and this helped Prof. Tsien’s group develop a kaleidoscope of GFP-like proteins that shine with all the colours of the rainbow.

"As a whole, fluorescent proteins have had a huge impact on many areas of biological sciences because they gave [scientists] a direct link from genes and DNA to something you can see inside a cell or inside any organism," Prof. Tsien is quoted as saying on his website.