Alice Ting’s movies won’t fill any theaters, but they are breaking ground in using what’s called “fluorescence imaging” to reveal the minute inner workings of cells in unprecedented cinematic detail.
To make her biology-in-action movies, Ting, an assistant professor of chemistry at MIT, needed a bright and efficient light source. So her lab developed a way to, effectively, glue superbright fluorescent “tags” directly to proteins of interest. The standard way to make proteins glow is to use green fluorescent protein (GFP), originally isolated from jellyfish, and cousins that fluoresce in different colors. But these proteins produce relatively dim light, making it difficult to see single molecules or in vivo processes. They also have to be genetically fused to the proteins being studied; this can alter the proteins’ behavior and prevent them from freely moving around and into cells. In contrast, Ting used quantum-dot tags that are up to 100 times brighter than GFP and interfere less with the observed proteins.
Other labs had labeled proteins with quantum dots–nanocrystals that fluoresce in different colors depending on their size–but attached them with the help of bulky antibodies. Ting’s lab did away with these clunky connectors and, at the same time, created far more secure ones, fusing small protein “linkers” to both the quantum dots and the proteins of interest. Ting then used an enzyme to join her two linkers, and voilà–she could observe a living cell in action. Nor is the linking system limited to quantum dots: it can be used for any tag.
“Alice Ting is a true innovator and is one of the best chemists of her generation,” says Timothy Swager, chair of MIT’s chemistry department. “Scores of research groups around the world are already applying her methods.” One of Ting’s latest projects is to fluorescently image the junction between nerve cells, illuminating a biochemical process that appears to play a key role in learning and memory. So it may be possible one day to see an actual film of how a brain learns. “Mammalian cells are so beautiful and funky,” says Ting–with the appreciation of a true director.