Jellies to GFP
The Story: Drifting along the currents off the west coast of N. America, the jellyfish Aequoria victoria gives off bursts of blue luminescence when a protein called aequorin binds calcium. The blue light is absorbed by another protein with the unimaginative name of green fluorescent protein (GFP), and the jellyfish now glows…surprise…green! After scientist Osamu Shimomura first observed that GFP could fluoresce independently of any added factors, Doug Prasher cloned the GFP gene and worked out its DNA sequence. At Prasher’s seminar, Martin Chalfie realized the potential of GFP: he could insert the gene behind any promoter (on switch) and the cell would glow green when the gene was turned on. Prasher handed out the cloned gene to Chalfie and hundreds of labs. This led to a multitude of uses of GFP, now a favorite workhorse in any research lab. Roger Tsien tinkered with the gene to generate a rainbow of different colors. Sadly, when Shimomura, Chalfie and Tsien were awarded a Nobel (in 2008) for their work, Prasher was conspicuously omitted, because no more than 3 can share the prize. Worse, he was out of a job by then, driving a courtesy shuttle bus for Toyota (apparently he is back in lab now). Still, Prasher expressed his delight over the Nobel, and he was invited to the ceremony and publicly thanked by his more fortunate colleagues.To paraphrase Newton, if we have seen further, it is by standing on the shoulders of giants.
The Science: GFP is built like a barrel of crisscrossing ribbons known as beta strands. Nestled in the middle, is a strange cyclical arrangement that spontaneously forms from three consecutive amino acids (Serine, Tyrosine, Glycine or SYG in their single letter code). It is this cyclical arrangement that gives GFP the ability to fluoresce. The same sequence in other proteins does not cyclize or fluoresce. Adjusting the environment around this changes the spectral properties (color), stability (so it can be used in warm blooded animals), and regulation (by pH or ions).
The Gift: Oh GFP, how do I love thee? Let me count the ways. Care to snoop on the business of your favorite protein? Tag it with GFP and become a video voyeur, watching it move in a living cell. Want to measure the pH (acidity) of a cell? There’s a pH-sensitive GFP mutant named pHluorin for that. Curious if two proteins interact? Tag one with YFP (glows yellow), another with CFP (glows cyan). When they come together, the emission from CFP activates YFP and you get a yellow signal. Create a Brainbow by genetically mixing GFP variants so each neuron is colored differently. Can you blame me for the bad poetry? 🙂
Pop Sci: http://imgur.com/gallery/krNEH
Nobel Lectures: Follow the links in http://goo.gl/51d40L #ScienceEveryday