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Researchers often want to know when and where a particular gene is “turned on” inside an organism. How do they accomplish such a feat? When genes are on, they produce telltale proteins. Unfortunately, it’s no good looking for these directly; proteins are much too small to see, even with the most powerful microscopes. Over the years, scientists have come up with a number of innovative workarounds. Here’s a particularly bright (green) one:

Illustrations by H. Adam Steinberg

Tag the gene. Scientists splice the gene for Green Fluorescent Protein (GFP) to the end of their gene of interest. This way, when the gene is expressed, it will produce a protein with a GFP “tail” attached to its end.

Transfer the tagged gene. The methods used to deliver this extra DNA vary from organism to organism. For the common fruit fly, by way of example, a tiny needle is used to inject the DNA into early fly embryos.

Switch on the black light. GFP, originally discovered in a naturally fluorescing jellyfish, emits green light after absorbing certain wavelengths of UV light. This makes the cells expressing tagged genes glow bright green, while cells with no gene activity remain black. With special microscopes, scientists can see exactly which cells inside an organism are producing these glowing proteins, and then monitor changes in those protein levels over time.

GFP shows changes in a cell over time.

Location, location, location. For researchers trying to develop safe genetic therapies, it’s vitally important that they be able to control where therapeutic genes are expressed inside the body. Using GFP-tagged proteins, scientists can quickly determine whether a new gene therapy approach targets the correct organs or tissues. To make this kind of analysis possible in larger organisms, scientists introduced GFP into the core DNA of several lab animals, including mice, cats, pigs and fish.