In 2017, Nathan Shaner and his colleagues found something unusual in the blue-green waters off Heron Island. As the group of scientists snorkeled the reefs surrounding the coral cay on the southern end of Australia’s Great Barrier Reef, one spotted a strange-looking jellyfish in the water. The researcher netted it and brought it back to the boat. When the scientists took a closer look, they noticed that the creature’s translucent body was shot through with luminous lines of blue.
The team wasn’t looking for jellies, but Shaner—an optical probe developer at the University of California, San Diego—collected the animal anyway. “Just on a whim, we said, ‘Well, it’s kind of blue, let’s take it home,’” he says.
Now, Shaner and his team have identified five fluorescent proteins in the body of the jellyfish previously unknown to science. The discovery may lead to new techniques for exploring how genes are expressed in cells, and potentially the brightest green fluorescent protein tag ever.
When Shaner and his team got the blue jellyfish—Aequorea australis—back to the lab, they prepared a sample for analysis. After sequencing its transcriptome—the genes expressed in the jelly’s body—Shaner was surprised to find several for light-producing proteins similar to green fluorescent protein (GFP), which scientists have used for decades to track proteins in cells and even create glow-in-the-dark cats. (Three researchers won a Nobel Prize in 2008 for the discovery and for the development of GFP as a fluorescent probe.) The original protein, known as avGFP, is found in the related A. victoria jellyfish; it has led to dozens of bioengineered GFP variants, some of which glow other colors like cobalt blue and turquoise.
Further analysis revealed the jelly A. australis produces five fluorescent proteins. These include two that glow green, two more that are blue under white light, and one that switches between yellow and clear when exposed to light, Shaner and colleagues report on the preprint server bioRxiv.
The researchers then took a second look at the original GFP jelly, A. victoria, from the Birch Aquarium at Scripps Institution of Oceanography in San Diego, California, and found genes for four more previously unknown fluorescent proteins. Some proteins from both jellies had narrow excitation and emission peaks, meaning they absorb and emit light at very specific wavelengths. This could make it easier to study the expression of multiple genes at once, using several different colors of fluorescent protein tags. The brightest protein, called AausFP1, was nearly five times brighter than GFP that had been enhanced for more powerful fluorescence.
“Fluorescent proteins are sort of like a Swiss army knife—everyone has a different use for them depending on what they’re trying to study,” Shaner says. “But brighter is always better for pretty much everyone. Hopefully, this will actually enable people to see things that they couldn’t see before.”
Besides being bright, AausFP1 doesn’t lose its glow when exposed to light, meaning that it could be used to image cells for an extended amount of time. Shaner reports he was able to photograph the protein continuously for 2.5 days; a normal GFP variant would bleach out within just a few hours.
The study is exciting, says Joachim Goedhart, a fluorescent protein engineer at the University of Amsterdam who was not involved with the work. “They came back with a lot of different and new promising variants.” Still, he says, the fluorescent proteins will need to be modified to make them useful to scientists. Improvements could include mutations to make them smaller, brighter, and easier to manipulate within cells, he says. “There’s still some work to do.”