Colorful creature: This sleeping baby monkey expresses GFP with the gene for the mutant Huntington protein. These animals are being used by researchers to study Huntington’s disease.
Martin Chalfie, now chair of the biological sciences department at Columbia University, was the first to demonstrate GFP’s value as a genetic tag. Chalfie realized that if the gene for GFP could be connected to the gene for another protein, then it would be possible to watch that gene switch on under the microscope. In 1994, Chalfie demonstrated the technique in a tiny worm called C. elegans, which has fewer than a thousand cells. He attached the GFP gene to part of a C. elegans gene that’s only expressed in six of the animal’s cells; under a microscope, these six cells glowed green.
Chalfie’s work demonstrated that GFP could tell biologists if a cell was expressing a particular gene. Roger Y. Tsien, a professor of biochemistry at the University of California, San Diego, built on the work of both Shimomura and Chalfie by developing many variations on GFP, each of which glows a different color, allowing researchers to track different biological processes within the same cell. By experimenting with variations in the sequence of the GFP gene, Tsien developed proteins that fluoresce in shades of blue and yellow. After Russian researchers developed a complex red fluorescent protein, Tsien also created a simpler-to-use version.
“It is imperative for researchers to map and understand the role of different proteins and their interactions in real time in the body,” says Elias Zerhouni, director of the National Institutes of Health, in a statement. “Understanding how this protein machinery malfunctions will increase our knowledge about potential causes of illness and disease and perhaps lead to better treatments.”