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Researchers find out how to genetically alter squid: traits



On the left is an unmodified hatch of a long-land squid (Doryteuthis pealeii). The one on the right was injected with CRISPR-Cas9 targeting a pigmentation gene before the first cell division. It has very few pigmented cells and clearer eyes.

Karen Crawford


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Karen Crawford

The first genetically modified squid has scientists excited about a potential new way to study such strange sea cries, sometimes compared to alien life forms.

Scientists report this week that they have disabled a pigmentation gene in a squid called Doryteuthis pealeii. Its success demonstrates that cephalopods (which include squid and octopus) can eventually be studied with the same type of genetic tools that have allowed scientists to explore the biology of more familiar laboratory animals such as mice and fruit flies. . They are easy to preserve in the laboratory, and scientists routinely modify their genes to obtain information about behavior, disease, and possible treatments.

Cephalopods may seem strange enough without scientists having grimaces at their genes. These tentacle beings have huge, intelligent brains that don̵

7;t look like anything of their own. They travel with jet propulsion and some can change their skin color in an instant. All this strangeness is exactly why some biologists want to understand them better.

“These big brains and this completely independent behavioral sophistication have evolved,” says Joshua Rosenthal, a researcher at the Marine Biological Laboratory in Woods Hole, Massachusetts. “This provides an opportunity to compare them with us and see what elements are in common and what elements are unique.”

Until now, research on cephalopods has been hampered by the fact that there has been no way to manipulate squid or octopus genes. Rosenthal is part of a group that is trying to change all that. The team is gathering a wide range of exotic cephalopod species, everything from flaming cuttlefish to pygmy octopus, to figure out how to keep them in captivity and alter their DNA.

Researchers are also working with a famous local squid that lives in the waters around Woods Hole. Historically, this squid has been important to neurobiologists because it has a giant, easy-to-study nerve cell. Much of what is known about how nerve cells send electrical signals comes from studies on this cell and research led to a Nobel Prize in 1963. In addition, scientists have sequenced the DNA that makes up the genetic code of this squid.

Every summer, a research boat leaves the Woods Hole and collects the squid. Doryteuthis pealeii. Karen Crawford of St. Mary’s College of Maryland, a key member of the research team, had previously discovered how to take sperm and eggs from this squid and produce embryos in the lab.

Studies with the Doryteuthis pealeii squid, shown above, they have led to important advances in neurobiology.

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Studies with the Doryteuthis pealeii squid, shown above, they have led to important advances in neurobiology.

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Based on this work, she and her colleagues realized how materials are injected that can alter the gene in the fertilized egg, to disrupt a gene involved in the coloration of skin and eye cells. Rosenthal states that the biggest challenge was going through a hard outer layer surrounding the squid embryo.

“For months, we would have broken needles,” he says. “So we found a way to get the injection needle. In the end, that turned out to be one of the most important blockages in this study.”

The resulting squid creatures had far fewer of the few dark spots that are normally characteristic of the species, because the pigmentation gene was removed from almost every cell.

“For me, that’s changing the game. I’ve been interested in trying to understand how these animals work from the molecular level, and so now we have the ability to go in and test what an individual gene does,” says Carrie Albertin, a another member of the research team who also works in the marine biological laboratory.

“That’s honestly, if you had asked me five years ago if we could do it, you would have just made me laugh and I would have said,‘ I dream it. “But, you know, I didn’t think it would be possible. And yet we’re here,” Albertin says.

These Doryteuthis pealeii Squid embryos were injected with CRISPR-Cas9 at different times before the first cell division, resulting in mosaic embryos with different characteristics.

Karen Crawford


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Karen Crawford

This species of squid cannot be raised to maturity in the laboratory, but is too large. But there are a lot of smaller squid and octopus species, and the team is already working to transfer the technology to those growing in captivity. Researchers are also looking to add genes, rather than deleting existing ones.

The work has thrilled other squid biologists such as Sarah McAnulty of the University of Connecticut. He has studied Hawaiian squid and says researchers have tried to genetically alter cephalopods in the past.

“It’s incredibly impressive that they’ve made it work and that’s a breakthrough for cephalopod researchers around the world,” McAnulty says. “We should all make bottles of champagne. That’s amazing.”

Rounded squid tack on the long shore, D. pealeii.

Karen Crawford


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Karen Crawford

Rounded squid tack on the long shore, D. pealeii.

Karen Crawford

When biologists study natural squid, they eventually “reach a wall of understanding,” because they can’t play with the animal’s genetics to explore how their systems work at the most basic level, McAnulty says. She believes that the ability to genetically modify cephalopods should make all sorts of new experiments possible.

“If I could do anything, I would start playing completely with the squid’s immune system,” McAnulty says, trying to figure out how, for example, the Hawaiian squid knows not to attack some kind of bright symbiotic bacteria that lives inside it.


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