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Using CRISPR to edit coral

In a proof-of-principle study, Stanford scientists and colleagues used the CRISPR/Cas9 system to modify genes in coral, suggesting that the tool could one day aid conservation efforts.

Some 30 years ago, the world saw its first big global coral bleaching take place -- an event that killed more than 15 percent of the ocean's reefs. Since then, as temperatures continue to rise, so have rates of coral bleaching, leaving scientists scrambling to find new conservation strategies to protect this beloved ocean animal (coral is an animal, not a plant) and the ecosystem it supports.

Now, researchers at Stanford have turned to CRISPR, a gene-editing tool that allows for quick and accurate changes in the DNA of organisms. And for what appears to be the first time, scientists have successfully edited the genes in a type of widespread coral found in the Great Barrier Reef.

Before you start to worry, let me clarify: no -- researchers are not making genetically modified super-coral and tossing it back into the ocean to spread far and wide.

What they're after is far more basic than that. Our press release explains:

Cleves' work, conducted in collaboration with researchers at UT-Austin and the Australian Institute of Marine Science, sprouted from a conversation at an international coral meeting that aimed to concretely understand the genes behind coral survival.

Are there some genes that render corals more resilient to spikes in ocean temperatures? Or perhaps a gene that helps establish new coral colonies? Scientists had hypothesized answers to these questions, but to truly know, Cleves wanted to create a technique that could allow coral biologists to answer such questions more rigorously.

'We want to use CRISPR-Cas9 with the express interest to start understanding what genes are critical to coral biology,' Cleves said.

The work was published online in the Proceedings of the National Academy of Sciences. Phillip Cleves, PhD, a postdoctoral scholar at Stanford and coral enthusiast, is first author on the study.

Until this study, such genetic tinkering had yet to successfully reach the branching, spiny, scaffold of the seafloor -- mostly due to the fact that this coral spawns infrequently, and the CRISPR tactic requires a zygote (or fertilized egg) to work.

Cleves and his collaborators were able to use CRISPR to successfully introduce mutations to three genes (red fluorescent protein, green fluorescent protein and fibroblast growth factor 1a, a gene that is thought to help regulate new coral colonization) in a specific type of coral, Acropora millepora, definitively showing for the first time that the gene-editing technology could be successful in coral species.

...The scientists made a type of genetic tweak that knocked out the genes, rendering them incapable of functioning. In the case of the red and green fluorescent proteins, determining if CRISPR worked would be easy -- like seeing lights switch off. Or so they hoped. However, it turns out that there are multiple copies of red and green fluorescent-protein genes. So knocking out one copy didn't put a stop to the glow altogether.

'Although we are not sure we saw convincing loss of fluorescence, DNA sequencing showed us that we were able to molecularly target both the red and the green fluorescent protein genes,' Cleves said. This showed the researchers that, in one go, CRISPR could successfully alter multiple genes if the two were similar enough -- a boon to genetic manipulation, as genes are often duplicated during evolution.

As for the third gene, fibroblast growth factor 1a, which only has one gene copy, post-CRISPR sequencing showed success: in some embryos, the gene was largely mutated, suggesting that CRISPR will work well to modify single-copy coral genes.

The study is a proof-of-principle, and still in very early days. Any contributions to the conservation of reefs are still on the distant horizon, but Cleves is hopeful that this research will provide a "blueprint" of the kinds of genetic manipulations that scientists can start performing with CRISPR.

Photo by Petra Lundgren, Juan C Vera, Lesa Peplow, Stephanie Manel and Madeleine JH van Oppen

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