Dietary omega-3 fatty acids are key nutrients that have beneficial health effects playing a critical role in the immune system as well as contributing to the normal function of the heart and development of the brain. The human body is unable to produce omega-3, which is why it is important to eat these essential fats. Fish and seafood are unique sources of omega-3 in the human diet, but decline in traditional fisheries means that more than half of all fish consumed is now farmed. Until recently the only way to ensure high levels of omega-3 in farmed fish and seafood was to deliver these nutrients in feeds by using the marine ingredients, fishmeal and fish oil. However, paradoxically, they too are derived from marine fisheries that are at their sustainable limit making them finite and limited resources. The rapid expansion of fish farming in the last two decades has ony been possible with increasing dilution of the traditional marine ingredients with more economical alternatives, primarily plant meals and vegetable oils that lack the omega-3 fatty acids found in fish. Therefore, the development of these alternative feeds in Atlantic salmon (Salmo salar) farming has seen levels of omega-3 in farmed salmon halved in recent years. Dietary omega-3 are equally essential for the health of fish, just as they are for humans. Several negative issues related to farmed fish performance and health have paralleled the development of alternative, low marine feeds with reduced levels of the beneficial omega-3, including higher incidence and severity of inflammatory diseases. However, in addition, inflammation is a key component of the immune response to all pathogens, including parasitic, bacterial and viral infections and so the current low levels of omega-3 in feeds for farmed fish has had consequences for fish health and welfare. Thus, the dual impacts of reduced dietary omega-3 levels on fish health, and the nutritional quality of farmed fish products for human consumers has meant that fish farming, especially of salmon, has spearheaded efforts to both highlight and close the gap between supply and demand for the key omega-3 nutrients. Specifically, the Global Salmon Initiative announced a tender for commercial organisations to supply up to 200,000 tons annually of novel omega-3-rich oils. In addition, a consortium including The World Bank, announced the F3 (Fish Free Feed) Fish Oil Challenge to create a fish-free 'fish oil' substitute. Consequently, new sources of omega-3-rich oils from marine microalgae and genetically-modified oilseed crops have been developed and tested as feed ingredients for farmed fish, including salmon. While these studies have proved the effectiveness of these new oils in increasing omega-3 content of farmed fish, the impact on fish health has been neglected. This project will directly investigate the important health impacts of entirely novel omega-3 rich oils as feed ingredients for farmed Atlantic salmon. The studies will focus on determining not only impact of the new omega-3 sources on the response of salmon to specific disease and parasite challenges, but also on defining the biochemical and molecular mechanisms underpinning fish health, quantifying the potential of these new dietary oils for use in UK salmon farming. The proposal is timely and highly relevant and appropriate as it responds to current needs with cutting edge research to improve the quality and effectiveness of modern alternative feeds in fish farming, enhancing production and feed efficiency, while maintaining the health and improving the nutritional quality of farmed fish, delivering greater sustainability and food security.

Farmed salmon is a major source of high quality protein and fatty acids essential for human health. Salmon aquaculture is worth approximately £1Bn to the UK economy, and supports many rural and coastal communities. However, sea lice are a major perennial problem for salmon aquaculture worldwide. These parasites attach to the skin of salmon and feed on tissue, mucus and blood. Infected fish show impaired growth and increased occurrence of secondary infections. They cause significant negative impacts on salmonid health and welfare, while lice prevention and treatment costs are a large economic burden for salmon farming, over £800M per annum. Encouragingly there is substantial genetic variation in resistance to sea lice both within and across salmonid species. While the commonly farmed Atlantic salmon are generally susceptible to infection, other salmonid species such as coho salmon are fully resistant. Improving the innate genetic resistance of the farmed salmon to sea lice is an environmentally friendly, but underexploited approach to lice control. Incremental improvements have been achieved via selective breeding of Atlantic salmon, but their long generation interval slows progress. Genome editing raises the possibility of rapidly increasing the resistance of salmon via precise targeted changes to their genomes; the key is knowing which specific genes to target. This project focusses on understanding the genetic mechanisms underlying resistance to sea lice, and identifying gene targets for genome editing to develop lice-resistant Atlantic salmon. To identify target lice resistance genes for editing, several different approaches will be taken, each exploiting the latest genomic technologies. Firstly, whole genome sequences will be obtained from a large population of farmed salmon on which sea lice counts following challenge have been collected. These will be used to map individual genes that contribute to variation in resistance in the commercial Atlantic salmon population. Secondly, it is known that the mechanisms underlying resistance to sea lice are due to a successful localised immune response close to the attachment site of the louse. Therefore, a detailed gene expression comparison of the immune response of Atlantic and coho salmon in the first four days following a lice challenge will be undertaken, using single cell sequencing approaches to highlight different responses in distinct cell populations at louse attachment sites. This will be complemented by profiling of the gene expression of the lice, and identification of potential immunomodulatory proteins and their targets in the host. Thirdly, genome editing approaches will be used to assess the impact of perturbing candidate resistance genes on response to sea lice both in cell culture and in the fish themselves. The former will be used to assess the cellular response to proteins secreted from the sea lice, and the consequences of knocking out each of the target genes on that response. This will lead to a final set of target genes for editing in salmon embryos, after which the edited fish will be challenged with sea lice. The resistance of the edited fish compared to full sibling control fish will then be assessed. The scientific programme of the project will be complemented by co-development of a strategy for the breeding and dissemination of edited lice resistant salmon, together with industrial partner Benchmark PLC. Furthermore, public and stakeholder engagement events are planned to communicate the research plans and outcomes, with a particular focus on the benefits and risks of genome editing in aquaculture. A successful outcome of lice resistant salmon would have major animal welfare and economic impacts via prevention of outbreaks, and removal of the need for chemical treatments. It would also provide a high profile example of the power of genome editing technology to understand biology and to improve food security and animal health.

Sustainable and profitable aquaculture in the UK relies on high quality stock. In contrast to terrestrial agriculture, the sources of stock for aquaculture species range from use of wild stock for several species, to pedigree-based breeding programmes incorporating genomic tools in salmon. Well managed programmes of domestication and breeding have huge potential for cumulative gains in production, including by preventing infectious disease outbreaks. Barriers to applying such approaches in commercial aquaculture include knowledge gaps in the genetic basis of economically important traits, and a lack of genetic tools and expertise applied to aquaculture. 'AquaLeap' establishes a leading interdisciplinary hub focused on innovation in aquaculture genetics to enable each sector to take a 'step' or 'leap' forward in stock enhancement. We will target advances for four species of economic importance or potential for UK aquaculture; European lobster (Homarus gammarus), European flat oyster (Ostrea edulis), lumpfish (Cyclopterus lumpus) and Atlantic salmon (Salmo salar). For each of these species, we will develop genomic tools and methods which will then be used to tackle industry-defined barriers to progress in stock enhancement. The genomic tools include high quality reference genome sequences using cutting-edge sequencing technology for the species for which they are currently lacking (lobster, oyster, lumpfish). These genome sequences will be used to exploit standard (e.g. single nucleotide polymorphism, SNP) and novel [e.g. copy number variation (CNV) and epigenetic modifications] sources of variation. Gene editing techniques will be developed, as this technology is likely to lead to breakthroughs in addressing aquaculture problems in the near future. Lobsters are a high value species with potential for diversifying UK aquaculture. Building on previous studies into the on-growing of hatchery-reared lobsters in aquaculture systems, and using the aforementioned genomic tools, we will assess the contribution of genetic and epigenetic variation to growth and survival traits. These results will inform selective breeding, hatchery conditions and choice of juveniles for on-growing, and has potential to improve the performance of lobsters at sea. Native oysters have declined dramatically in recent years, and there is significant interest in restocking from both an aquaculture and ecological perspective. A major barrier to hatchery-based restocking and production is the parasitic disease Bonamia. We will build on previous genomic tool development to identify SNP markers that can be used to predict breeding animals with innate resistance to Bonamia, informing selection of native oysters for stocking and tackling a major production issue. Lumpfish are used extensively as cleaner fish for biological control of sea lice in salmon farming. Hatchery reproduction is now possible, and the next step is selective breeding for traits to enhance their robustness and performance. To help facilitate this, we will assess wild stock diversity to inform base populations for breeding, to estimate genetic parameters for production traits, and develop SNP marker panels for stock management. Breeding of salmon is advanced, and uses genomic tools to enhance trait improvement and inbreeding control via genomic selection (GS). We will apply innovative approaches to improve the cost-efficiency of GS, and test these approaches for the emerging aquaculture species. We will assess the role of potential novel sources of genetic variation (CNVs) in gill health traits. Finally, we will use gene editing to modify a specific gene causing resistance to a viral disease in salmon, with a view to future editing of salmon genes to improve resistance to infectious diseases. The scientific programme is complemented by a series of training, dissemination and public engagement activities, including addressing skills gaps identified by the ARCH-UK network.

Phytoplankton (algae) are essential in marine ecosystems determining fisheries productivity however around 2% of marine phytoplankton species produce biotoxins that can accumulate in harvested shellfish, posing a threat to human health. Harvesting of shellfish, including mussels, scallops and oysters, is an important part of the UK aquaculture industry worth around £40 million per annum and supporting over 3,000 rural jobs. The harvested shellfish are an important source of protein with markets at home and abroad. There is significant potential to expand this industry, however, harvesting can be halted, particularly in the summer months, due to the presence of harmful algae in the sea which can accumulate in the filter feeding shellfish. Monitoring of water and shellfish for the presence of biotoxins helps determine if it is safe to harvest, and where closure occurs it has been reported to cost a single farm in excess of £160,000 per annum. This consortium brings together three new technologies and world class expertise to provide an early warning, near instant biotoxin detection and a system to protect harvesting sites during harmful algal events. This is a unique opportunity to exploit research three separate developments initially funded by RCUK, allowing their deployment to be expertly utilised through the direct collaboration of shellfish farmer, government regulators and trade associations. The first of the exciting new technologies is the e-mice, so called because although in a single small (6x12x6 cm) electronic instrument we aim to detect all groups of regulated biotoxins with the potential to include other biotoxins which may be regulated in the future. Not so long ago consumer safety was ensured by the use of a mouse bioassay, this has now been replaced by sophisticated analytical detection systems. Currently it takes around 1-week and multiple methods to obtain results however, the e-mice will be developed to provide a format that can be used at a shellfish harvesting site and give instant results supporting rapid management decisions regarding harvesting or protection of the shellfish grounds. Detecting toxicity once it has already accumulated can often limit the management options therefore this collaboration includes the satellite-based early warning system called ShellEye which will help predict harmful algae events and particularly their location with respects to shellfish harvesting areas. Data obtained from satellite imagery will be correlated with phytoplankton monitoring and biotoxin detection in phytoplankton samples. Early warning will then be used to make decisions on when to use the third of the innovative technologies which is the photocatalytic curtain. Also, pioneered under a different RCUK research project, the TiO2-based catalytic pods have specifically been designed to facilitate the treatment of biotoxins and algae in reservoirs in developing countries. The work planned here will explore their optimum configuration for use in a marine environment in a way that will protect harvesting sites, hence the concept of the reactive curtain. The benefits of using this technology is that no chemicals are discharged into the water, the catalyst when illuminated produces high energy, short life hydroxyl radicals which destroy organic molecules and can be active against microorganisms. The project will be underpinned by developing the capacity to produce all the required, phytoplankton, biotoxins and reference material to fully validate the e-mice during development and field use while also supporting photocatalytic optimisation. The culmination of the project will be the development of an integrated management strategy where all partners from industry, the regulators and academics will contribute to a practical close to real-time monitoring and protection of shellfish harvesting areas. This will in turn limit harvesting loses and ensure confidence to support expansion of this aquaculture industry.

Fish diseases are a huge threat for the aquaculture industry and for global food security. Some of the most important disease-causing organisms in aquaculture are part of the oomycetes or watermoulds, in particular Saprolegnia parasitica, Saprolegnia diclina and Saprolegnia australis are causing serious fish losses. Collectively, these fungal-like organisms are responsible for at least 10% annual mortalities in most salmon hatcheries and freshwater sites. Consequently, Saprolegnia ranks among the most important pathogens of Atlantic salmon. Unfortunately, over the last few years the incidences of saprolegniosis outbreaks in Scottish farms have significantly increased. Indeed, some sites have had very high losses due to saprolegniosis. Whereas other farms have remained largely disease free. The reasons as to why some farms are badly affected and others seem to avoid disease outbreaks, with apparent identical welfare standards and husbandry management practises, are at present completely unclear and form the main rational for the current application. Our hypothesis is that several risk factors (pertaining to fish, pathogens and the environment) are playing a synergistic role in suppressing immunity in fish towards Saprolegnia, which lead to outbreaks of saprolegniosis. Therefore, we propose a concerted industry-wide, industry-led and industry-supported research programme to discover, map, model and understand the main drivers, risk factors, that allow saprolegniosis outbreaks. A "big data" resource will be created that will be scrutinised with statistical methods to identify the main risk factors and conditions for outbreaks of saprolegniosis. Undoubtedly, identifying the main, or a combination of, risk factors will greatly aid the salmon aquaculture industry to pre-empt any future outbreaks and would lead to an integrated approach to saprolegniosis management, which would result in increased welfare standards, improved fish health, fewer losses and a reduction in production and treatment costs.