In the summers of the 1960s, a biologist called Osamu Shimomura discovered a glowing jellyfish on one of his fishing trips in the Pacific ocean. This jellyfish glowed green when agitated, which triggered Prof. Shimomura to find out what protein was responsible. He isolated the protein, and noted that it glowed under ultraviolet light. He called it the Green Flourescent Protein (GFP), and the rest, as they say, is history. Shimomura went on to win a Nobel Prize in Chemistry in 2008 for his work in the discovery of GFP, along with two other scientists, Martin Chalfie and Roger Y. Tsien.
Today GFP is one of the most used tool to visualize structures in cells under the microscope. In cell biology, it is important to be able to see cells and microbes under the microscope, since most forms of life are transparent and fairly colorless. GFP has been used since its discovery to do just this. The most exciting discovery that has made GFP the staple of cell biology is its ability to be used as a fluorescent tag for proteins within the cell. The GFP protein is so small that its sequence can be glued together with the sequence of another protein, producing a fluorescent version of the protein of interest. In this way, scientists can watch the behavior of their protein of interest in its natural environment under the microscope.
In the beginning however, there were serious problems. The protein was not stable enough. It faded quickly under the intensity of the UV light illumination. It could not be produced at the temperature that most cells live in. So scientists began to make small mutations in the sequence of the protein to see how this would affect it. One mutation resulted in a much stronger, more stable green color. Another changed the color of GFP from green to cyan, yellow and blue, giving rise to Cyan FP, Yellow FP and Blue FP. These days, many more mutations have resulted in even more colors.
Assistant Professor Joachim Goedhart is a researcher who has developed these colored variants of the GFP protein at the University of Amsterdam in The Netherlands. I had the pleasure of interviewing him at his lab, where he showed us Esterichia coli cultures which contained different forms of fluorescent protein, resulting in spectacular colored bacterial colonies that are viewed under UV light. Joachim hopes that his plasmids help other researchers in visualizing their favorite proteins, either on one their own or in combination with other proteins.
These bacteria were featured over the holidays in 2018 during our lab talks. Our audience was wowed by bacteria on plates glowing green, red, yellow, and blue Christmas trees, snowflakes and even the Grinch.
Take a look at the video of Joachim making these plates.