Working towards lice-resistant salmon

£1.7m study aims to identify genetic mechanisms that could make Atlantic salmon resistant to a key parasite.

A type of salmon’s ability to withstand sea lice may hold the answer to preventing the pest’s devastating effects in other fish.

Different species show varying resistance to sea lice – while Atlantic salmon is susceptible, coho salmon is almost completely resistant.

A team of scientists is investigating the coho salmon’s genes, in a bid to understand its resistance to sea lice. They hope to recreate the effects in Atlantic salmon, which are severely affected by the disease.

Sea lice are a large and perennial problem for salmon aquaculture globally, severely affecting fish health and welfare, and costing the global aquaculture sector around £800m per year.

These parasites attach to the skin of salmonid fish and feed on tissue, mucus and blood, often causing open injuries and stress. Infected fish show impaired growth and increased occurrence of secondary infections.  

While the parasites are able to initially attach to coho salmon, the fish mount an innate immune response that results in fast sea lice rejection and limited disease.

Researchers will study the response to lice attachment exhibited by coho salmon, and seek to reveal the biological processes underlying genetic resistance to these parasites.

They will then apply knowledge gained concerning these mechanisms of resistance to Atlantic salmon. In particular, aiming to identify genes that could make Atlantic salmon resistant to sea lice.

Ultimately, researchers will aim to introduce the mechanisms of genetic resistance found in coho salmon to Atlantic salmon aquaculture populations, by making alterations to their DNA.

The project is led by researchers from the University of Edinburgh’s Roslin Institute and the University of Stirling’s Institute of Aquaculture, and will receive a total of £1.7 million from the Biotechnology and Biological Sciences Research Council (BBSRC) and the Sustainable Aquaculture Innovation Centre (SAIC). It is an industrial partnership award with aquaculture breeding company Benchmark Genetics.

Shortlisting genes

Researchers will use data previously collected from 12,000 infected Atlantic salmon to identify regions of the genome associated with resistance to sea lice.

Data will enable them to test if there is a common underlying genetic basis to variation in resistance of Atlantic salmon to different sea lice species, to map individual resistance genes, and to improve prediction of lice resistance.

Comparing high and low resistance Atlantic salmon will provide insights into resistance mechanisms within the species. Scientists will compare skin and the live parasites attached to it to assess resistance and to measure precisely when lice are rejected by resistant fish.

Differences in resistance may be due to actions of specific cells, and the location where lice attach to salmon skin comprises multiple cell types. Researchers will compare Atlantic salmon with coho salmon at single cell resolution to investigate the key mechanisms, genes and proteins involved in their different responses to lice.

Information gathered throughout the project will be integrated to identify and shortlist potential sea lice resistance genes.

Gene editing will be used to validate those genes, through tests examining the effects of silencing them using novel in vitro models. If the edit causes changes to resistance to lice, that provides additional evidence that the gene is associated with resistance.

Five shortlisted candidate gene edits will be introduced into salmon embryos using the CRISPR gene-editing method.

Edited salmon will then be exposed to sea lice to assess their resistance compared to their unedited siblings. This step will identify effective edits, with potential for commercial application to create lice-resistant salmon.

Introducing DNA changes

Gene editing, which enables targeted, precise changes to the genetic code, has been used in previous studies by scientists from the Roslin Institute to identify disease resistance genes in salmon.

Subject to regulatory and public approval, this would be transformative, with huge financial, environmental, and animal welfare benefits, researchers say.

Alternative conventional control strategies, such as feed supplements, cleaner fish, and tailored cage design, are only partially effective. Medicines, which are expensive and potentially environmentally damaging, are still frequently required to control sea lice, many of which have evolved resistance to common delousing drugs.

Selective breeding to increase resistance of salmon to lice is an effective but relatively slow process because a generation of salmon takes up to four years to reach maturity for reproduction.

Improving the innate genetic resistance of salmon to lice is a promising, environmentally low impact, yet underexploited approach to lice control.

While Atlantic salmon is highly susceptible to sea lice, coho salmon is practically fully resistant. We are going to compare the genomes of the two species to understand how they are linked to their response to these parasites, so that we can identify the key mechanisms underlying resistance in coho salmon. We can then attempt to transfer these resistance mechanisms from coho salmon to Atlantic salmon via genome editing.

Gene editing has potential to expedite the breeding of disease-resistant salmon by making targeted changes, informed by years of research into the genetic and functional mechanisms of resistance to sea lice.

Welfare and sustainability

Work by the consortium aims to improve fish health and enhance the sustainability of the salmon aquaculture sector.

Dr Robledo highlights the benefits of tackling these parasites: “Sea lice-resistant salmon would improve fish welfare, reduce the environmental impact of delousing treatments, reduce the potential impact of sea lice on wild fish, and contribute to secure jobs in the sector.” 

Professor James Bron, Professor of Aquatic Animal Health at the University of Stirling, said “The University of Stirling’s Institute of Aquaculture brings more than 30 years’ research into the interactions of sea lice and Atlantic salmon to this collaboration. Advances made in disease control for Atlantic salmon aquaculture are relevant to the culture of other key species, so developing and applying these cutting-edge technologies helps to increase aquaculture sustainability and global food security.”

Breeding fish with improved resistance to disease will reduce the need for antibiotics and other drugs to prevent the impact of parasites. This reduction of chemicals in the environment and the loss of fewer fish to disease will subsequently decrease the environmental impact of aquaculture.

Genetic improvement results in stocks that are more resistant to problematic infectious diseases, and also require less feed to grow to market size. This can improve animal welfare while also improving production efficiency and reducing their carbon footprint.

Heather Jones, CEO of SAIC, said: “This project is a great example of the diverse and innovative work that is being undertaken in Scotland to tackle the perennial challenge of sea lice. The health and welfare of fish is of paramount importance to our aquaculture sector, and it is very encouraging to see world-leading research take place in our institutions. We are pleased to help fund this initiative, supporting increased economic impact with a reduced environmental footprint in UK aquaculture.”

Future improvements

Genetic technologies could be used to introduce other desirable traits into farmed species, such as improved growth, resistance to other diseases, or robustness in diverse farming environments.

Most aquaculture species can produce many offspring, and large populations with improved genetics can be bred quickly for improved production performance.

Monitoring how a farm populations’ genome varies between individuals will help maintain genetic diversity as they develop.

Research into farmed fish, including their response to disease, is undertaken at the recently opened freshwater Aquaculture Genetics Research Facility at the Roslin Institute. The facility supports research into disease resistance and genome editing of farmed fish, in particular salmon, oyster and shrimp.

Roslin scientists have previously identified genes and regions of the genome of fish linked to diseases such as those caused by Infectious Pancreatic Necrosis Virus and Tilapia Lake Virus.

With regard to implementation of gene editing in aquaculture, Dr Robledo says: “Within current legislation, gene-edited fish cannot be farmed in the UK. If this were to be approved by policymakers and the public, researchers and the aquaculture sector would have to assess how to introduce edited fish into farm settings. For instance, edited fish might need to be sterile to prevent them from mixing with wild stocks. Sterility would need to be compatible with a breeding programme with fertile animals at its centre, and this will require technological innovation.”

Salmon was the first approved genetically modified food, and has been made available in the US and Canada. Production of the AquAdvantage fish, which has been modified to overexpress growth hormone, enabling year-round growth, is produced in indoor facilities to prevent fish from mixing with or impacting on wild populations.

Further research into genetics and health could help make these technologies even more precise and contribute to aquaculture sustainability, food security, and animal welfare.

** The Roslin Institute receives strategic investment funding from the BBSRC and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies.  **