CRISPR-Cas9 may help battle sea lice in Atlantic salmon

Photo: Helge Skodvin/Nofima NOFIMA skodvin-nofima-maroy-25-1024x400.jpg
Lice attach to the Atlantic salmon skin and feed on blood and mucus. If untreated, the parasites can create sores that stress and can ultimately lead to death of the fish.
Study to draw on natural abilities of Pacific salmon to fight sea lice.

Sea lice are naturally occurring parasites that attach to and feed on salmon. Infestations on salmon farms can be common and can severely affect the welfare of fish if left unchecked, according to Norwegian research organization Nofima.

Sea lice are one of the biggest challenges facing the global aquaculture industry, and existing methods for preventing lice infestation are not entirely effective. Lice wound and stress the fish, which can lead to death if left untreated, but the most effective methods of treatment (such as mechanical de-lousing) can also substantially stress the fish, Nofima said. Furthermore, common therapeutics can be damaging to wild ecosystems, and lice frequently develop drug resistance, making the treatments less effective.

Innovation in the salmon industry and strict rules help keep the severity of infestation low, but at a high price for the farmed salmon, which often have to be treated to remove the sea lice, Nofima said. The aquaculture industry is, therefore, looking for an environmentally friendly solution that can effectively limit lice attachment with little/no negative impacts on fish welfare.

Now, researchers are aiming to apply a new Nobel Prize-winning methodology in a way that could make farmed salmon an unattractive host for sea lice.

A typical salmon farm contains many potential hosts for lice and provides ideal conditions for the lice to mature and reproduce, Nofima said, meaning salmon farms can promote the multiplication of lice. If the number of sea lice attached to farmed salmon and the ability of the lice to mature and reproduce could be suppressed, the reduced numbers of lice would benefit both farmed salmon and passing wild salmon.

According to Nofima, research has shown that several species of Pacific salmon are unattractive to sea lice. Detailed research is needed to uncover the genetic basis for these differences and to see if this knowledge can be utilized in a way that helps prevent sea lice infestation among farmed Atlantic salmon.

In an effort to provide solutions to the sea lice problem, genetics researchers at Nofima -- along with partners from the U.K., the U.S., Canada, Sweden and Australia and fish breeding and production companies -- are embarking on a groundbreaking new project with funding from the Norwegian Seafood Research Fund.

“It is no exaggeration that the knowledge we create in this new project could transform the Norwegian aquaculture industry if Atlantic salmon can be made to be highly or completely resistant to lice,” said Nofima senior researcher and project leader Nick Robinson, who has extensive experience from genetic and breeding research on disease resistance in aquatic species farmed worldwide.

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of a gene editing method utilizing CRISPR-Cas9 “genetic scissors,” which is the method the researchers in this project will use as an ultimate test of which genes affect how attractive salmon are as a host to lice.

Genomic differences make Atlantic salmon more attractive hosts to lice than coho or pink salmon, Nofima said. Such differences, for example, could result in the production of chemical attractants by Atlantic salmon but not by coho or result in an effective defensive response of the salmon skin to newly attached lice in pink salmon but not in Atlantic salmon.

The research aims to find the genetic basis for these differences between Atlantic and North American salmon species, Nofima said.

“If we can reveal the differences in the genetic code that cause lice to be attracted to Atlantic salmon or that makes the skin of North American salmon a bad place for sea lice to settle and develop, then it may be possible for us to use that information to make Atlantic salmon resistant to sea lice and have better health,” Robinson said.

CRISPR-Cas9 is tool that makes it possible to make targeted changes to the genetic code. For instance, CRISPR-Cas9 could be used to delete a few base sequences of the code to disrupt a gene’s function. However, an intense research effort is needed, first to determine which genes could be edited to have the desired effect and second to be able to successfully make the desired edits.

“CRISPR-Cas9 is still a relatively new technology in the aquaculture research but can allow for very precise and targeted changes at specific genes in the salmon genome known to be involved in cross-species variation in resistance to lice, and the success of its use depends on the type of change that is needed and on the position and code of the gene to be edited,” explained professor Ross Houston of The Roslin Institute in the U.K., whose team will work closely with Nofima on this and other parts of the project.

Promising genes

The researchers will find and measure the chemical components that each salmon species releases. Then, they will test how sea lice react to each of the unique chemicals released by Atlantic salmon and reveal which of them are semiochemicals that can attract or repel lice.

“We can observe whether lice are excited and stimulated to swim towards these chemicals,” partner Howard Browman of the Institute of Marine Research in Norway said.

The researchers will also undertake experiments to study the response to attached lice by different cell types in the salmon skin and how this response differs in the resistant North American species.

Finally, the researchers will determine what genes are affecting the production of these semiochemicals and affecting the response of different cells in the skin and will test how these genes can be “disrupted” using CRISPR-Cas9 to make Atlantic salmon unattractive to lice.

Tested thoroughly

If the researchers succeed in carrying out gene editing in the laboratory, the salmon must be thoroughly tested up to adult size in closed facilities to investigate how effective the change is and to reveal any potential unwanted side effects.

Robinson emphasized that this project will not make genetically edited fish available to industry and that further testing will be needed.

They will also consider risks of sea lice adapting to the changes in the salmon and how this would be best prevented. “Lice adapt to become resistant to chemical treatments, and we need to consider if they might adapt to overcome any specific changes that are made to Atlantic salmon,” partner Tim Dempster from the University of Melbourne in Australia added.

The project will also consider possible effects on wild salmon populations, Nofima said.

The project will be led by the Norwegian Fisheries, Aquaculture & Food Research Institute–Nofima and will involve close collaboration with research partners: The Roslin Institute (University of Edinburgh, U.K.), the Institute of Aquaculture (University of Stirling, U.K.), Rothamsted Research (U.K.), University of Melbourne (Australia), University of Prince Edward Island (Canada), Bigelow Laboratory for Ocean Sciences (U.S.), University of Gothenburg (Sweden) and Institute of Marine Research (Norway). Benchmark Genetics and Salmar are industry partners.

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