Proteins produced in the laboratory – research is moving forward
In Nofima's laboratories, scientists are making significant progress in their efforts to cultivate muscle cells from cattle and produce egg whites and milk proteins using yeast.
“Through our research, we’ve developed methods to cultivate bovine muscle cells on eggshell membranes. We’ve also been using a food-approved yeast to produce egg and milk proteins. Our next objective is to determine whether we can successfully scale up this production,” explains Senior Scientist Sissel B. Rønning at Nofima. She leads the ARRIVAL project, where most of this research is conducted.
Research on cultivated food in Norway began in 2018, with the onset of the GrowPro project. This was the first project on the topic funded by the Research Council of Norway (NFR). At that time, it was among the first international projects that focused on open, knowledge-based research. Since then, Nofima’s scientists have been thoroughly exploring new biotechnological processes for food production. The ARRIVAL project not only investigates biotechnological possibilities but also examines the societal opportunities and challenges associated with this type of food production.
Navigating the Future of Cultivated Meat: A Global Perspective and Norway’s Role
Advocates for cultivated meat and cell-ag proteins argue that these innovations can meet the growing demand for animal proteins due to population growth. They believe these alternatives can reduce greenhouse gas emissions, decrease land use, and water consumption, and improve animal welfare. However, opponents argue that these production methods could undermine traditional food and agricultural practices. They also call for more evidence to ensure the safety of human health.
A restaurant in Singapore has been serving chicken nuggets made from cultured meat for several years. Perfect Day, a US company, produces and sells milk proteins produced in yeast in the US and has just recently applied for a novel food approval, targeting the European market. Recently, the United States Food and Drug Administration approved the production of cultured chicken, and Israel has authorized the production of cultured beef. Conversely, Italian authorities are considering a ban on these products. France and Austria have also imposed restrictions, but not as stringent as Italy’s. The United Kingdom, Germany, Spain, and the Netherlands, on the other hand, are encouraging development by allocating funds and expediting approval processes.
Norway’s position on this issue is currently unclear. The Norwegian Board of Technology, a partner in the ARRIVAL project, plans to conduct a horizon scanning.
“We will begin with a comprehensive survey covering everything from technology and economics to consumer preferences and environmental impact. We will then identify focus areas and describe signals and trends. Based on these findings, we will develop recommendations and measures for policymakers,” says Tonje Nerby, a senior adviser at the Norwegian Board of Technology.
Cultivated Meat in Norway: Public perceptions and Priorities
Public opinion on cultivated meat varies widely. Some view it as an interesting, innovative, and environmentally friendly solution, while others find it unsettling and unnatural.
“In our study, we surveyed a thousand individuals, representing a diverse cross-section of Norway’s adult population. The most common associations with cultivated meat among Norwegians were ‘positive’, ‘interesting’, ‘unnatural’, ‘frightening’, ‘sceptical’, ‘innovative’, and ‘environmentally friendly’,” explains Senior Scientist Paula Varela-Tomasco at Nofima, who led the consumer study.
Interestingly, while 54 percent of the respondents had heard of cultured meat prior to the survey, over half were still uncertain about what cultured meat is. A new survey, targeting precision fermentation is now in the pipeline.
While taste typically tops the list in most surveys asking Norwegians about their food choices, this doesn’t hold true for cultured meat.
“In our study, we prompted participants to finish the sentence ‘I would eat cultured meat if…’. The majority responded with ‘it was cheap’, followed by ‘it was healthy’ and ‘it was safe’. Surprisingly, ‘it tasted good’ only came in as the fourth option,” confirms Paula Varela-Tomasco.
This is how we make the new proteins in the lab
At Nofima, scientists are attempting to create meat by cultivating muscle cells derived from cattle. “We’ve focused on identifying an edible, sustainable biomaterial that the cells can thrive on. Eggshell membranes, a byproduct, have proven to be a suitable medium as they contain structures like those in cattle and are rich in beneficial nutrients,” explains Senior scientist Mona E. Pedersen, who oversees this aspect of the project.
The process of producing animal food proteins in yeast is known as precision fermentation. “In our lab, we’re working on producing both egg and milk proteins. While this technology isn’t new—it’s been used since the 70s to produce insulin, for instance—what is novel is our use of it to create food proteins. We’re utilizing modern gene editing techniques, like CRISPR, to insert the gene for the specific protein we want to produce, enabling the yeast to yield the desired product,” says Senior Scientist Annette Fagerlund at Nofima.
The next phase involves testing the efficacy of scaling up and mass production.
Food produced in this manner is already available in the market in the US and several countries outside the EU, and numerous start-ups are aiming to replicate this success.
Skip to main content
How we work with gene editing at Nofima
Gene editing is a technique that Nofima has adopted in several of its aquaculture research projects. Here is some information about why and how Nofima uses this technique, along with references to some useful information for readers who would like to know more.
What is gene editing?
Gene editing is a collective term for genetic technologies that make targeted changes in the genetic material (DNA) of an organism. It could, for example, relate to removing or adding one or more bases to the DNA, or replacing one gene variant with another.
The most common technique is CRISPR/Cas9. You can read about how this technique works on Bioteknologiradet.no (the Norwegian Biotechnology Advisory Board).
What do we do at Nofima?
Nofima has approved facilities for working on gene editing in Ås, Tromsø and Sunndalsøra.
In our research we use this technique in studies involving fertilised salmon eggs, established cell lines, primary cells and bacteria. Gene editing is a valuable tool for examining the functions of individual genes.
The potential for gene editing lies in the fact that changes can be made quickly and directed. It is possible to see the effects of gene editing as soon as the effects on the trait can be measured.
We have included gene editing in our research on genes that control the fat metabolism in salmon, and in research on resistance to viruses and parasites. Disease resistance is important for reducing disease in farmed fish. All our gene editing projects relating to fish have a Responsible Research and Innovation (RRI) component. RRI means that societal stakeholders collaborate throughout the research process to adapt the process to values, needs and expectations from society.
About regulation and permits
Today gene editing is used on animals in Norway for research purposes only, i.e. when one wishes to discover the effects produced by different genes. Laws and regulations prohibit the use of gene-edited animals in food production in Norway and the EU. Gene editing is equated here with genetic modification, see the Bioteknologiradet.no for more information about legislation.
The reason for strict regulation is the uncertainty surrounding the possible risks to animals, consumers and the environment. Ethical considerations are important. There must be no risk of destroying nature for future generations or changing the balance of ecosystems.
The intrinsic value and welfare of animals is an important consideration. Alternative technologies also need to be considered in the same risk assessment. In some cases, e.g., when gene editing can substantially reduce or eliminate suffering, it may be unethical not to use gene editing. It is sometimes argued that it is not the techniques themselves, but the effects of the techniques that should be regulated in each case.
Conditions for using the tool
In addition to legal permits, there are a number of conditions that need to be in place in order to ensure that gene editing is a suitable tool in respect of food production. It is assumed that one knows exactly which part of the genome needs to be changed, what editing is required and what effects this has on the property being studied (as well as other properties).
What we know today is that most of the properties we are studying are not controlled by a single gene, but they have polygenic backgrounds, so the technique needs to be able to address this. It is also assumed that the technique used is precise and hits the right part of the genome, producing effects in all cells and not just in some (mosaic). It should preferably also be possible to use it on many individuals within a short period of time.
Atlantic salmon is eminently suitable for gene editing, partly because it has external fertilization, large eggs, a large number of eggs and slow cell division.
The reference genome for Atlantic salmon is known, but when compared to the development of knowledge about the human genome, developments are slow, which means that the preparatory work required in order to determine which genes should be edited often takes a long time.
Some projects
Skip to main content
Use of gene-edited cell lines in aquaculture
This project aims to explore the use of cell lines and primary cells, combined with gene editing to facilitate aquaculture research.
Background
Modern breeding programs often include a molecular component, where so-called genome-wide association studies (GWAS) are used to identify genomic areas where genes of interest for breeding are likely to be located. In addition, applied molecular research projects often lead to candidate genes for traits of interest, regardless of whether GWAS has been performed.
Nofima is an established institution when it comes to breeding programs in aquaculture, and we are also highly competent when it comes to analysis of associated molecular data. We are thus in a unique position when it comes to integrating observations from breeding with molecular observations.
Nofima has also built up solid expertise in gene editing of both fish cell lines and fertilized eggs using the CRISPR-Cas system.
Until recently, it has been extremely resource-intensive to confirm which genes are directly involved in relevant traits. Gene editing of fertilized eggs using the CRISPR-Cas system has been used, but this requires several years of breeding of (several generations of) fish and complicated analyses. This SIS project aims to identify gene function using cell lines and primary cells in combination with gene editing technology.
Goal
The goal of the project is to explore the use gene-edited cell lines in aquaculture research. Cell lines play an important role in both basic biology research, clinical research and applied research, and should provide a useful tool when trying to bridge the gap from gene to phenotype in aquaculture species such as Atlantic salmon and Atlantic cod.
Nofima has many projects where elucidation of gene function is an important component. Candidate genes are currently being pursued using traditional molecular methods, as well as gene-editing of fertilized eggs. However, production of pure gene-edited animals has proven extremely resource demanding and time consuming.
We believe Nofima is in a good position to establish itself as an attractive partner when it comes to running projects linking data from gene edited cell lines and primary cells, to traits relevant for aquaculture production. Both industry and academic institutions should be potential collaborators.
How we work
Nofima is involved in a number of projects that focus on characteristics we wish to modulate in production fish in order to improve food production. Examples include pathogen resistance (bacteria, amoebae, viruses, sea lice, etc.), fat metabolism, pigmentation, growth rates and sexual maturation. To establish the proposed research strategy, we will therefore focus on issues where studies have already been conducted and candidate genes identified.
The first aim of the project will be the purchase and establishment of relevant cell lines. In addition, there should be opportunities for sharing fish cell lines through collaborations with external partners (The Norwegian Veterinary Institute; VI and Norwegian School of Veterinary Science; NMBU).
We also expect increased expertise in establishing cell lines in-house, and develop robust protocols for gene editing. Gene editing will include knockout of genes, editing of regulatory areas, and knock-in of genetic elements.
Candidate genes from projects will be ranked based on previous knowledge, and their expression levels checked in available cell lines/primary cells. Cells that are deemed suitable candidates for a project will then be systematically gene edited.
A trait of particular interest is disease resistance. Cardiomyopathy syndrome (CMS) is a serious heart disease in farmed salmon that causes significant financial losses for the industry. Causal virus (piscine myocarditis virus; PMCV) cannot be cultivated, and breeding programs and the development of a vaccine to limit the disease have proven to be challenging. Other disease include ISA (Infectious Salmon Anemia) and HSMI (Heart and Skeletal Muscle Inflammation).
For these infectious diseases, susceptible cells will be gene edited to render them resistant. This should allow for the identification of genese critical for viral entry and virus replication.
Knowledge about relevant genes will be useful in breeding programmes and in efforts to mitigate diseases using other measures (drugs, feed etc.).
Worth knowing
Strategic priority areas
Nofima invests its own resources in order to increase competence in useful, relevant and innovative areas and strengthen our position among the leading applied research institutes.
Active projects
Some previous projects
Skip to main content
Harnessing cross-species variation in sea lice resistance
Do Pacific salmon species carry a secret they could share with Atlantic salmon? What is it in the genes that make these relatives of Atlantic salmon less susceptible to lice? Researchers is looking for the answers to these questions, using the gene editing method CRISPR-Cas9.
This project draws together a leading team of researchers from Norway, UK, USA, Canada, Sweden and Australia to discover the mechanisms underlying cross-species variation in host resistance to sea lice, and apply this knowledge to boost Atlantic salmon resistance.
Background
It is well established that certain Pacific salmon species are resistant to sea lice and are able to kill lice in the early stages of parasitisation, whereas Atlantic salmon are highly susceptible.
This difference is primarily due to variation in the effectiveness of the early-stage immune response, but immunomodulation by the lice is likely to play a key role. Improving the innate genetic resistance of the Atlantic salmon host to the lice is a highly promising but underexploited approach to sea lice control.
Objective
The main objective is to elaborate and document the potential for utilising genetic traits and mechanisms of salmon lice resistance in Pacific salmon as tools to achieve an Atlantic salmon with high or full salmon lice (L. salmonis) resistance.
Subobjectives
- Identify and document genes and mechanisms responsible for the difference in salmon lice resistance between salmonid species.
- Elaborate and document the potential for utilising the identified genetic traits and mechanisms of salmon lice resistance as tools to achieve an Atlantic salmon with high or full salmon lice resistance.
- Conduct a risk evaluation on the possibilities for, and consequences of salmon lice adapting to Atlantic salmon with salmon lice resistance.
What we do
In this project we are focussing on two main potential mechanisms underlying inter-species variation affecting louse parasitisation.
- Firstly, we will compare the host-parasite interaction in the early stages of louse attachment in detail using transcriptomic and proteomic profiling of tissue sampled from attachment sites.
- Secondly, we will evaluate differential attractiveness to host-specific semiochemicals across species using louse behavioural analysis.
Integrating results across these two research arms will enable shortlisting of high priority candidate genes for perturbation using genome editing of salmon embryos. Sea lice challenge testing will assess resistance to lice in the edited fish in comparison to unedited family-matched controls. Together with our major industry partners, protocols for breeding and disseminating edited fish as part of ongoing breeding programmes will be designed to limit inbreeding, enable concurrent improvement of other important traits, and minimise the risk of lice evolving to overcome the host resistance.
Outcomes will include fundamental knowledge of mechanisms affecting genetic resistance to sea lice, leading to infection outcomes in Atlantic salmon more closely resembling the resistant Pacific species, together with pathways to implementation to transform the Norwegian salmon farming sector.
This project builds on previous individual and collaborative research projects led by the project leaders at all the institutions in the fields of functional genomics, host-parasite interaction, breeding, preventative lice infestation strategies, risk analysis, semiochemical detection and testing and genome editing.
Ethical guidelines
It is up to the aquaculture industry and the authorities, in consultation with other stakeholders, to determine whether these new tools can be deployed. The project will fully explore the potential for using gene editing to prevent lice infestation for salmon farming.
The researchers will follow so-called RRI guidelines (responsible research and innovation).
“We will invite NGOs and others who are interested in seafood production to get input on what social and moral consequences the research and possible implementation could have for Norwegian society. With such input, we can adjust the work underway and create a responsible plan that balances animal welfare, ethics and law”, says project leader Nick Robinson.
The work
Work package 1: Mechanisms of resistance to sea lice
Elucidation of host-parasite interactions before and after contact with L. salmonis will be evaluated using diverse approaches, harnessing the interdisciplinary background of our project team. Transcriptomics, proteomics and semiochemical profiles of two resistant (coho and pink) and two susceptible (Atlantic and chum) salmon species will be compared, assessing all the different components of resistance: host immune responses, host attractiveness and lice immunomodulation. We have chosen these four species so that we can determine if the same factors affect resistance in all species. We chose chum because they are highly susceptible to lice and, unlike Atlantic salmon, chum, coho and pink are relatively undomesticated, often reared together and phylogenetically close.
The goal is to gain a detailed functional understanding of resistance and susceptibility, pointing to molecular processes and gene networks that can be modified by genome editing to transfer Pacific salmon resistance to Atlantic salmon.
Subobjective: Identify and document genes and mechanisms responsible for the difference in salmon lice resistance between species.
Work package 2: Potential to introduce sea lice resistance loci into Atlantic salmon stocks using genome editing
Genome editing of candidate genes selected based on the results of WP1 will be used to test the effectiveness of transferring sea lice resistance from Pacific species to Atlantic salmon. This WP will also explore how breeding technologies can be most effectively used to disseminate putative resistance loci.
Subobjective: Elaborate and document the potential for utilising the identified genetic traits and mechanisms of salmon lice resistance as tools to achieve an Atlantic salmon with high or full salmon lice resistance.
Work package 3: Risk analysis and modelling of the potential for sea lice to evolve to overcome genetic resistance
This WP integrates a risk analysis on the potential of sea lice to evolve to adapt to resistant salmon. A key plank of our implementation plan will be to minimise the risk of adaptation by lice. We can assume from what data is already available that without mitigation strategies any new adaptations in sea lice could rapidly increase in frequency along the Norwegian coast, rendering resistant salmon ineffective.
Subobjective: Conduct a risk evaluation on the possibilities for, and consequences of salmon lice adapting to Atlantic salmon with salmon lice resistance.
Immune against sea lice?
Do Pacific salmon species carry a secret they could share with Atlantic salmon? What is it in the genes that make these relatives of Atlantic salmon less susceptible to lice?
In this short video you will learn what researchers do to find answers to these questions.
Videos of presentations and discussions we take part in
Project leader Nick Robinson of Nofima gave a presentation at the North Atlantic Seafood Forum 8.6.21 with the title “New genetic technologies and approaches for understanding and improving Atlantic salmon resistance to sea lice”
Nofima scientist Tone-Kari Knutsdatter Østbye, who is working with CrispResist, was invited for a conversation at the Litteraturhuset in Trondheim 15.9.21 about gene editing. The title was «Er vi klare for en bioteknologisk laks?» (Norwegian language)
Østbye also took part in a seminar arranged by the Norwegian Biotechnology Advisory Board 27.11.21 titled “Åpent møte om CRISPRsalmon: Bør vi genredigere oppdrettslaksen?” (Norwegian language)
Nick Robinson and Andrew Coates each presented their research at the 13th Sea Lice Conference International 2022 in the Faroe Islands (9-13 May 2022):
Sarah Salisbury at the Roslin Institute won the best pitch prize at the ISGA conference in December 2022 in Chile, for this pitch of her research in the CrispResist project
Tone-Kari Østbye from Nofima and Rolf Brudvik Edvardsen from Institute of Marine Research, talked about the project at the Norwegian NRK Radio in October 2023. Other stakeholders were also interviewed. Starts 35:10 into the recording.
Publications
Local inflammation at the salmon louse (Lepeophtheirus salmonis) attachment site contributes to copepodid rejection in coho salmon (Oncorhynchus kisutch)
Cell and Tissue Research,
2025
Academic article
Transcriptomic characterization of transitioning cell types in the skin of Atlantic salmon
BMC Biology,
2025
Academic article
Keratinocytes drive the epithelial hyperplasia key to sea lice resistance in coho salmon
BMC Biology,
2024
Academic article
Evolutionary predictions for a parasite metapopulation: Modelling salmon louse resistance to pest controls in aquaculture
Evolutionary Applications,
2023
Academic article
A guide to assess the use of gene editing in aquaculture
Reviews in Aquaculture,
2023
Academic literature review
Transcriptomic landscape of Atlantic salmon (Salmo salar L.) skin
G3: Genes, Genomes, Genetics,
2023
Academic article
Policies to promote breeding for lice-resistant salmon: Incentives designed for resilient and sustainable growth in aquaculture
Journal of Fish Biology,
2023
Academic article
A metapopulation model reveals connectivity-driven hotspots in treatment resistance evolution in a marine parasite
ICES Journal of Marine Science,
2022
Academic article
How are genetic technologies being applied to combat infectious diseases in aquaculture?
The Fish Site thefishsite.com,
2022
Article in business/trade/industry journal
Applying genetic technologies to combat infectious diseases in aquaculture
Reviews in Aquaculture,
2023
Academic literature review
Evolusjon av lakselus mot kontroll- og forebyggende tiltak
Norsk Fiskeoppdrett,
2021
Article in business/trade/industry journal
Genomics, gene-editing and the blue revolution
Pursuit,
2020
Article in business/trade/industry journal
Skip to main content
Gene editing for CMS resistance in salmon
Identify and validate candidate genes for CMS resistance in Atlantic salmon through state-of-the-art gene editing.
Gene editing is a new technology that has potential to provide new opportunities for breeding to improve production efficiency and disease resistance.
Cardiomyopathy syndrome (CMS) is a disease which causes economic losses and adversely affects the welfare of fish in Norwegian aquaculture.
Use of state-of-the-art gene editing technologies for improvement of CMS resistance is likely to be highly beneficial for the Atlantic salmon aquaculture.
Our previous studies have located areas in the genome that contain genes affecting CMS resistance.
This project will identify candidate genes and evaluate their function in laboratory cultured heart cells and in fish.
The project will also develop and assess the effectiveness of breeding strategies employing gene editing for creating CMS resistant salmon, and design and assess the potential of a special schemes aiming to deliver gene edited salmon fingerling to suppliers.
The ethical, social and legal implications of developing CMS resistant salmon using gene editing will be investigated. Active responsible research and innovation (RRI) processes for gene editing will be promoted with stakeholders.
The project will create a knowledge base and example for the industry regarding disease management through state-of-the-art gene editing; this will greatly improve the bioeconomy and sustainability of Atlantic salmon production.
Publications
Detection of causative genes for resistance against cardiomyopathy syndrome in Atlantic salmon using omics data
2023
Academic chapter/article/Conference paper
A guide to assess the use of gene editing in aquaculture
Reviews in Aquaculture,
2023
Academic literature review
Policies to promote breeding for lice-resistant salmon: Incentives designed for resilient and sustainable growth in aquaculture
Journal of Fish Biology,
2023
Academic article
Contact persons
Research facts
Much of the research has been carried out in the project ARRIVAL of Cellular Agriculture-Enabling Biotechnology for Future Food Production with the short name ARRIVAL. The project is funded by the Research Council of Norway and led by Nofima. Other partners are Østfold University College, Norilia AS, Nortura SA, Ruralis, Sintef Industri, the Norwegian Board of Technology and TINE AS.
The consumer study has been carried out in the strategic research programs “Precision” and “FoodForFuture”, and the development of methods for gene editing of yeast has been carried out in the strategic research program “FutureFoodControl”. These are funded by the Fund for Research Levies on Agricultural Products.
