WE CAN now spy on the very molecules of life with unprecedented precision. By tagging proteins with a burst of light, researchers have found they can track their hectic movements.
“It isn’t often appreciated how dynamic proteins are or how important that is,” says Jennifer Lippincott-Schwartz, who developed the technique with George Patterson at the National Institutes of Health near Washington DC. Far from being mere bags of fluid, our cells have complex structures and internal highways. Many proteins move between compartments, interact with other proteins or even leave the cell to rush elsewhere in the body.
The usual way to track the movements of a particular protein – let’s call it X – is to fuse it with a green fluorescent protein from a jellyfish that glows when light hits it. This allows X to be seen under the microscope, wherever it is. The trouble is that every X molecule lights up at once, making it hard to follow single molecules over time.
Advertisement
But the NIH team has discovered a mutant form of the fluorescent protein that normally hardly glows at all. If it is hit by a burst of blue laser light, however, the protein fluoresces 100 times as brightly when light is shone on it. This activation is permanent, so if a laser is used to “paint” proteins in one area of the cell, they can then be followed for as long as they survive (Science, vol 297, 1873).
“It’s the most important innovation in the field since green fluorescent protein itself was introduced,” says Thomas Jovin of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany. He says it could be used to screen drugs to see if they can disrupt protein movements linked with disease.
The technique should also lead to many new insights. Already, the NIH team has discovered that there’s surprisingly rapid exchange of proteins between lysosomes, the compartments that act as the garbage disposal of cells. And Jovin’s team is now adapting the system to study growth factors that play a role in animal development and cancer biology.