Understanding the CD163 - PRRS virus interaction to improve genetic engineering for resistance
Lead Research Organisation:
University of Edinburgh
Department Name: The Roslin Institute
Abstract
Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic viral disease of pigs that causes major economic losses. The causative agent of PRRS, PRRS virus (PRRSV) is a rapidly evolving small enveloped RNA virus. Whilst improvements have been effected with changes in husbandry and vaccination, PRRS still has major impacts on pig health and welfare. PRRS accounts for about a third of the cost of infectious disease to the US pig industry amounting to $650M per year. PRRS is the most costly disease to pig industries of Europe, China and North America and new PRRSV variants have the potential to be even more devastating as demonstrated by recent outbreaks of highly pathogenic variants of the virus in China and Southeast Asia.
PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. Like all viruses PRRSV relies on the host cell machinery to replicate itself and generate new viral particles. One of these host proteins, CD163, has been found to be essential for the virus' escape from the uptake vesicle during the entry process by membrane fusion. CD163 is expressed on the surface of macrophages and the extracellular portion of CD163 forms a pearl-on-a-string structure of nine scavenger receptor cysteine-rich (SRCR) domains. SRCR domain 5 (SRCR5) was found to be essential for PRRSV's ability to infect a host cell. In addition to mediating PRRSV infection, CD163 has a variety of important functions within the host cell, such as removing haemoglobin-haptoglobin complexes from the blood, thereby preventing the formation of reactive oxygen species that could damage other cells.
My recent research together with others demonstrated that genome editing is a viable tool to combat PRRSV infection and confirmed the importance of CD163 in in this process. Work by another research group has shown that pigs in which the CD163 gene was knocked-out are resistant to PRRSV infection. However, the expression and function of CD163 in these animals is completely abolished and thus their ability to remove haemoglobin/haptoglobin complexes from blood, ischaemic repair and inflammation response may be impaired. My work removed SRCR5 by deletion (deltaSRCR5) of the encoding exon from the pig genome. I found that macrophage cells from these animals were not only resistant to PRRSV infection but also expressed the truncated deltaSRCR5 CD163 on the macrophage surface whilst maintaining haemoglobin-haptoglobin scavenger function.
It is expected that removal of SRCR5 and thereby destruction of the "lock" abrogates the key-lock interaction of PRRSV with its receptor. Thereby, it prevents fusion of PRRSV with the host cell membrane. However, we do not understand enough of the CD163-PRRSV interaction to exclude the potential for this highly mutagenic RNA virus to adapt to a deltaSRCR5 cell or pig. Therefore, we need further understanding of the CD163 - PRRSV interaction and insight into PRRSV's ability to adapt to the deltaSRCR5 modification. My research on deltaSRCR5 shows that removal of a single exon from CD163 can abolish PRRSV infection, emphasising the great power of genome editing technology to induce subtle genetic changes.
The aim of this project is to further assess the CD163 - PRRSV interaction and the potential of the PRRSV to adapt to a deltaSRCR5 pig as well as to generate even more subtle changes to the pig genome than exist in the current deltaSRCR5 pigs. I propose the following strategies to address these questions: to identify domains and amino acids of CD163 interacting with PRRSV; to assess the PRRSV-CD163 signalling and interactome; to serially passage PRRSV on cells from deltaSRCR5 pigs to mimic virus evolution; to produce functional deltaSRCR5 pigs by exon skipping rather than exon deletion.
PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. Like all viruses PRRSV relies on the host cell machinery to replicate itself and generate new viral particles. One of these host proteins, CD163, has been found to be essential for the virus' escape from the uptake vesicle during the entry process by membrane fusion. CD163 is expressed on the surface of macrophages and the extracellular portion of CD163 forms a pearl-on-a-string structure of nine scavenger receptor cysteine-rich (SRCR) domains. SRCR domain 5 (SRCR5) was found to be essential for PRRSV's ability to infect a host cell. In addition to mediating PRRSV infection, CD163 has a variety of important functions within the host cell, such as removing haemoglobin-haptoglobin complexes from the blood, thereby preventing the formation of reactive oxygen species that could damage other cells.
My recent research together with others demonstrated that genome editing is a viable tool to combat PRRSV infection and confirmed the importance of CD163 in in this process. Work by another research group has shown that pigs in which the CD163 gene was knocked-out are resistant to PRRSV infection. However, the expression and function of CD163 in these animals is completely abolished and thus their ability to remove haemoglobin/haptoglobin complexes from blood, ischaemic repair and inflammation response may be impaired. My work removed SRCR5 by deletion (deltaSRCR5) of the encoding exon from the pig genome. I found that macrophage cells from these animals were not only resistant to PRRSV infection but also expressed the truncated deltaSRCR5 CD163 on the macrophage surface whilst maintaining haemoglobin-haptoglobin scavenger function.
It is expected that removal of SRCR5 and thereby destruction of the "lock" abrogates the key-lock interaction of PRRSV with its receptor. Thereby, it prevents fusion of PRRSV with the host cell membrane. However, we do not understand enough of the CD163-PRRSV interaction to exclude the potential for this highly mutagenic RNA virus to adapt to a deltaSRCR5 cell or pig. Therefore, we need further understanding of the CD163 - PRRSV interaction and insight into PRRSV's ability to adapt to the deltaSRCR5 modification. My research on deltaSRCR5 shows that removal of a single exon from CD163 can abolish PRRSV infection, emphasising the great power of genome editing technology to induce subtle genetic changes.
The aim of this project is to further assess the CD163 - PRRSV interaction and the potential of the PRRSV to adapt to a deltaSRCR5 pig as well as to generate even more subtle changes to the pig genome than exist in the current deltaSRCR5 pigs. I propose the following strategies to address these questions: to identify domains and amino acids of CD163 interacting with PRRSV; to assess the PRRSV-CD163 signalling and interactome; to serially passage PRRSV on cells from deltaSRCR5 pigs to mimic virus evolution; to produce functional deltaSRCR5 pigs by exon skipping rather than exon deletion.
Technical Summary
Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic viral disease of pigs that causes major economic losses. The causative agent of PRRS, PRRS virus (PRRSV) is a rapidly evolving small enveloped RNA virus infecting cells of the monocyte/macrophage lineage.
The macrophage cell surface protein involved in PRRSV fusion was found to be CD163. Out of the nine scavenger receptor cysteine-rich (SRCR) domains that form a pearl-on-a-string structure as the extracellular part of CD163, SRCR domain 5 (SRCR5) was found to be essential for PRRSV's ability to infect the host cell. Recent work by me and others demonstrated that genome editing can be a viable tool to combat PRRSV infection and confirmed the importance of CD163 in PRRSV infection. Work by another research group has shown that pigs in which the CD163 gen has been knocked out are resistant to PRRSV infection. However, the expression and function of CD163 in these animals is completely abolished and could have negative effects on the animals. My work removed SRCR5 by deletion of the encoding exon from the pig genome. I found that macrophage cells from these animals were not only resistant to PRRSV infection but retained expression of the truncated deltaSRCR5 CD163 on the macrophage surface, preserving the haemoglobin-haptoglobin scavenger function of the protein.
The aim of this project is to further assess the CD163 - PRRSV interaction and the potential of the PRRSV to adapt to a deltaSRCR5 pig as well as to generate even more subtle changes to the pig genome than exist in the current deltaSRCR5 pigs. I propose the following strategies to address these questions: to identify domains and amino acids of CD163 interacting with PRRSV; to assess the PRRSV-CD163 signalling and interactome; to serially passage PRRSV on deltaSRCR5 to mimic virus evolution; to produce deltaSRCR5 pigs by exon skipping using CRISPR/Cas9 homology directed repair.
The macrophage cell surface protein involved in PRRSV fusion was found to be CD163. Out of the nine scavenger receptor cysteine-rich (SRCR) domains that form a pearl-on-a-string structure as the extracellular part of CD163, SRCR domain 5 (SRCR5) was found to be essential for PRRSV's ability to infect the host cell. Recent work by me and others demonstrated that genome editing can be a viable tool to combat PRRSV infection and confirmed the importance of CD163 in PRRSV infection. Work by another research group has shown that pigs in which the CD163 gen has been knocked out are resistant to PRRSV infection. However, the expression and function of CD163 in these animals is completely abolished and could have negative effects on the animals. My work removed SRCR5 by deletion of the encoding exon from the pig genome. I found that macrophage cells from these animals were not only resistant to PRRSV infection but retained expression of the truncated deltaSRCR5 CD163 on the macrophage surface, preserving the haemoglobin-haptoglobin scavenger function of the protein.
The aim of this project is to further assess the CD163 - PRRSV interaction and the potential of the PRRSV to adapt to a deltaSRCR5 pig as well as to generate even more subtle changes to the pig genome than exist in the current deltaSRCR5 pigs. I propose the following strategies to address these questions: to identify domains and amino acids of CD163 interacting with PRRSV; to assess the PRRSV-CD163 signalling and interactome; to serially passage PRRSV on deltaSRCR5 to mimic virus evolution; to produce deltaSRCR5 pigs by exon skipping using CRISPR/Cas9 homology directed repair.
Planned Impact
Who will benefit from this research?
The potential non-academic beneficiaries of this research include pig breeding companies, pig producers and ultimately the entire chain of users of pig products, including meat packers, processors, retailers and consumers. There are also potential benefits to the biotechnology sector.
How will they benefit from this research?
PRRS is the most costly disease to pig industries of Europe, China and North America and new PRRSV variants have the potential to be even more devastating. Thus, the development of novel and/or more effective strategies to control PRRS will improve the sustainability of the pig industry and potentially reduce the cost of pig products.
In the pig breeding sector the research outputs will have the potential to inform future breeding programmes. The pig breeding industry has already incorporated selection for desirable disease resistance genes into breeding programmes. To date selection for disease resistance has been limited to diseases for which susceptibility is determined by a single major gene. Moreover, breeding for disease resistance is constrained by the nature of any genetic variation in susceptibility to infection. Whilst evidence for genetic variation in host responses to infection with PRRSV exists, the genetic control of these responses is polygenic and there is no evidence to date of major genes conferring complete resistance to PRRSV. With increasing capabilities to genetically modify farmed animals there are opportunities to engineer resistance. The recent demonstration that such genetically-engineered, PRRSV-resistant pigs can be generated shows the potential impact of such pigs for the pig industry. Further research into these animals is thus not only timely but also necessary to assure breeders and consumers alike that genetically-engineered pigs do not present a long-term risk for virus evolution.
Public acceptance of genetically modified animals remains uncertain, especially in Europe. However, the development of non-transgenic pigs engineered for enhanced disease resistance using genome editing technology, which introduces no exogenous DNA, has the potential to re-shape the debate. Moreover, given the impact of PRRS in key markets such as North America and China where genetically edited animals are potentially acceptable, beneficial impacts could be delivered to the pig industry within 3-5 years of project completion.
The potential non-academic beneficiaries of this research include pig breeding companies, pig producers and ultimately the entire chain of users of pig products, including meat packers, processors, retailers and consumers. There are also potential benefits to the biotechnology sector.
How will they benefit from this research?
PRRS is the most costly disease to pig industries of Europe, China and North America and new PRRSV variants have the potential to be even more devastating. Thus, the development of novel and/or more effective strategies to control PRRS will improve the sustainability of the pig industry and potentially reduce the cost of pig products.
In the pig breeding sector the research outputs will have the potential to inform future breeding programmes. The pig breeding industry has already incorporated selection for desirable disease resistance genes into breeding programmes. To date selection for disease resistance has been limited to diseases for which susceptibility is determined by a single major gene. Moreover, breeding for disease resistance is constrained by the nature of any genetic variation in susceptibility to infection. Whilst evidence for genetic variation in host responses to infection with PRRSV exists, the genetic control of these responses is polygenic and there is no evidence to date of major genes conferring complete resistance to PRRSV. With increasing capabilities to genetically modify farmed animals there are opportunities to engineer resistance. The recent demonstration that such genetically-engineered, PRRSV-resistant pigs can be generated shows the potential impact of such pigs for the pig industry. Further research into these animals is thus not only timely but also necessary to assure breeders and consumers alike that genetically-engineered pigs do not present a long-term risk for virus evolution.
Public acceptance of genetically modified animals remains uncertain, especially in Europe. However, the development of non-transgenic pigs engineered for enhanced disease resistance using genome editing technology, which introduces no exogenous DNA, has the potential to re-shape the debate. Moreover, given the impact of PRRS in key markets such as North America and China where genetically edited animals are potentially acceptable, beneficial impacts could be delivered to the pig industry within 3-5 years of project completion.
Publications
Proudfoot C
(2017)
Genome editing for disease resistance in livestock.
in Emerging topics in life sciences
Burkard C
(2018)
Pigs Lacking the Scavenger Receptor Cysteine-Rich Domain 5 of CD163 Are Resistant to Porcine Reproductive and Respiratory Syndrome Virus 1 Infection.
in Journal of virology
Tait-Burkard C
(2018)
Livestock 2.0 - genome editing for fitter, healthier, and more productive farmed animals.
in Genome biology
Proudfoot C
(2019)
Genome editing for disease resistance in pigs and chickens.
in Animal frontiers : the review magazine of animal agriculture
Burkard C
(2019)
Gene edited "superpigs" resist devastating disease
in TheScienceBreaker
| Description | As previously demonstrated, genome edited pigs lacking the scavenger receptor cysteine rich domain 5 (SRCR5) of the CD163 protein are resistant to infection with porcine reproductive and respiratory syndrome virus (PRRSV). Here we have taken primary cells from these edited animals to assess whether the virus can evolve and overcome the barrier posed by the lack of SRCR5 in its entry pathway. In vitro evolution through serial passaging experiments of PRRSV-1 and PRRSV-2 on dSRCR5 CD163 primary pig macrophages shows no adaptation of the virus to the edited cells up to passage 50. Passaging on a 90/10 dSRCR5 CD163/ wild type cell mix was showing the same results. A minimal genome edit has been introduced into pigs resulting in an 11bp deletion at the splice-acceptor site of exon 7 of CD163, which encodes the SRCR5 domain of the protein. By breeding mosaic animals with the original SRCR5 deletion animals we are able to phenotypically characterise the animals for virus infection and other phenotypic aspects, whilst continuing the breeding lines. Results show both a skipping of exon 7 and a resulting CD163 protein lacking SRCR5 as well as refraction to infection of primary macrophages. Base-editors of the first generation were too inefficient to be used in the animal experiments. Using base editors in novel pluripotent stem cell technology allows us the differentiation of edited iPSCs into macrophages for assessing infectability. A publication on the novel minimal edit and in vitro evolution is in preparation. Unfortunately, CD163 proteomics had to be removed from the scientific programme of the grant due to COVID delays. |
| Exploitation Route | These findings could influence the further strategy of editing pigs for resistance to PRRSV infection. |
| Sectors | Agriculture, Food and Drink,Education,Government, Democracy and Justice,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic viral disease of pigs that causes major animal suffering and economic losses. In order to enter host cells PRRS virus (PRRSV) attaches to a small portion of a single pig protein called CD163. Using genome editing, the region of the pig CD163 gene encoding the small virus interacting portion was removed. This disrupted the interaction between PRRSV and the host cell and rendered pigs resistant to disease. Within the grant on hand we are continuing the investigations on the CD163-PRRSV interaction, whilst assessing the impacts of the genome editing on the pig's phenotype and the virus evolution. PRRS has a very strong economic impact on pork production, substantiated through animal loss or slowed growth, as well as increased biosecurity and biomedical costs exacerbated by secondary infections. The BBSRC industrial partnership award that funded the initial project to generate PRRSV-resistant pigs ("Engineering Resistance to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), BB/L004143/1) involved regular interaction with Genus plc, an international pig and cattle breeding company. As such a commercial impact route was considered from a very early stage, whereby Genus plc would integrate the PRRSV-resistance trait directly into their highly productive pig lines, combining the advances made through traditional breeding with genome editing. Genus operates internationally, ensuring that with appropriate approvals there can be distribution of PRRSV-resistant animals to breeders and farmers worldwide. To safeguard intellectual property, one patent application had been filed prior to me joining the project, with a second application filed based on my project results. I recognise that even with a robust IP position and a clearly defined route to commercial impact, there remain challenges before genome edited pigs arrive on consumers' plates. Both public opinion and the legal framework surrounding genome edited animals are major challenges facing our PRRSV-resistant pigs. Negative publicity surrounding transgenic technologies has resulted in general scepticism about biotechnology in animal breeding, although it has yet to be seen if this will encompass newer technologies such as genome editing. Engagement with multiple stakeholders (consumers, farmers, veterinarians, breeders, and policy makers) is required, in which we are transparent about both the benefits and limitations associated with the PRRSV-resistant pigs. Various modes of dissemination have been used to ensure communication of the results of the research on PRRSV-resistant pigs to stakeholders, encouraging public debate on the topic of PRRSV-resistant pigs and more broadly on applications of genome editing in livestock. One of the main challenges of this endeavour was to ensure sufficient breadth of both information and delivery routes. As both the research and the "product" involves animals, it was important to communicate openly about animal use in research, while stressing our goal of improved animal welfare intertwined with a positive impact for farmers worldwide. Together with the press and public relations team of the University of Edinburgh a media package detailing our research and the global value of our PRRSV resistant animals was generated. In order to be transparent about our use of animals we allowed the BBC to film not only the piglets, but also the surgical procedure involved in their generation. This was broadcast on The News at Ten. In the media there was broad reporting of our results, totalling over 12 national and 4 international broadcasts, over 20 national print and 40 national online formats, over 20 international online and print formats, and over 20 veterinary and pig related publications. The media package was awarded a Highly Commended by the Concordat on Openness on Animal Research in the UK in 2018. We believe we achieved a social impact by introducing the public to the potential welfare benefits that can be achieved through genome editing in livestock, encouraging wider debate on the issue. From a commercial perspective, our patent on CD163 genome edited pigs has been granted and licensed by our industrial partner, Genus plc. The SRCR5 deletion pigs have been generated on the background of their commercial nucleus breeder pigs. Within a rolling approval process with the US American FDA, pigs are being bred and challenged with PRRSV. Preliminary data from that process shows resistance to both PRRSV-1 and PRRSV-2 challenge in vivo. Phase I submission is completed and further data on the second generation pigs expected to be submitted in 2022. Furthermore, regulators from other countries have indicated they will likely follow an approval by the FDA. Approval of other genome edited pigs and other animals for human consumption, such as the GalSafe pigs in the USA or Madai red sea bream in Japan, are encouraging. The timeline estimated for broader approval and sale of animals is between 3 and 5 years. The beneficiaries of this research include anyone in the pork production chain, as well as the consumer and ultimately the general public. The pigs will have improved welfare as they will be resistant to a debilitating disease. PRRSV infection supresses the pigs' immune response, giving rise to severe secondary infections with other pathogens. Antibiotics use increases between 50-100% in the case of a PRRSV outbreak on a farm, which means eliminating PRRSV infection can also significantly reduce the antibiotics use. The reduced loss of animals and improved weight gain due to the absence of PRRS will reduce food waste in the production chain and increase productivity. Estimates in the US attribute around a 10% production loss in pig rearing to PRRS every year. Ultimately this will reduce costs for the consumer and aid food security. |
| Impact Types | Societal,Economic,Policy & public services |
| Description | Biochemical interaction of CD163 with PRRSV glycoproteins GP2, GP3, and GP4 |
| Organisation | Free University of Berlin |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | We are providing purified, tagged CD163 protein variations for the assessment of biochemical and biophysical interactions of the protein with the PRRSV glycoproteins GP2, GP3, and GP4 and glycoprotein complex GP2/3/4. |
| Collaborator Contribution | Our collaboration partners area analysing the biochemical and biophysical interactions of CD163 variants with the PRRSV glycoproteins GP2, GP3, and GP4 and glycoprotein complex GP2/3/4 using their established baculoviral expression system. |
| Impact | So far we are in the early stages of this collaboration and many protocols are still being optimised. |
| Start Year | 2018 |
| Description | CASE studentship uplift |
| Organisation | Eco Animal Health Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Eastbio CASE studentship on discovering new host-pathogen interactions to develop antivirals and vaccine strategies against PRRSV |
| Collaborator Contribution | Student stipend uplift, expertise, consumable uplift, travel uplift. |
| Impact | No outputs to list yet. |
| Start Year | 2019 |
| Description | Development of antiviral therapeutics against PRRSV |
| Organisation | Eco Animal Health Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Based on previous results and results obtained in this project, antiviral therapeutics are being developed in collaboration with Eco Animal Health. We are developing methods and testing the antiviral compounds as well as actively contributing to their improvement. |
| Collaborator Contribution | Eco Animal Health are developing, synthesising, and providing the compounds tested. At the same time, those compounds give us mechanistic insights into the interaction of CD163 with PRRSV. |
| Impact | A patent application at the end of 2019 has been reviewed favourably and is on a good path to get granted. A second patent application has been submitted. |
| Start Year | 2017 |
| Description | Maintenance of delta SRCR5 pigs |
| Organisation | Genus plc |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Breeding and maintenance of the genome edited delta SRCR5 pig line from the end of "Engineering resistance to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)" (BB/L004143/1) and the beginning of "Understanding the CD163 - PRRS virus interaction to improve genetic engineering for resistance" (BB/R004463/1). |
| Collaborator Contribution | Genus plc provided the funds for breeding and maintenance of the delta SRCR5 pigs. |
| Impact | The outcomes of this project are directly interlinked with the outcomes of the grants mentioned above. |
| Start Year | 2017 |
| Description | 'Science Insights 2022' - Research presentation |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Science Insights is a work placement programme for high school pupils about to enter S6 (final year at high school). Backgrounds and insights around animal biotechnology were presented to the pupils and inspired engaging discussions. |
| Year(s) Of Engagement Activity | 2022 |
| Description | BBSRC Animal Health Research Club Fourth Dissemination Event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | A retrospective report on the BBSRC Animal Health Research Club project on "Engineering resistance to Porcine Respiratory Syndrome virus (PRRSV)" was presented including the ongoing research in the BBSRC project " Understanding the CD163 - PRRS virus interaction to improve genetic engineering for resistanc" (BB/R004463/1) and outreach activities. This was followed by questions and discussions from/with scientists engaged in other BBSRC Animal Health Research Club and with representatives from the industrial co-funders of the BBSRC Animal Health Research Club. |
| Year(s) Of Engagement Activity | 2018 |
| Description | British Science Festival Hull 2018: "From lab to farmyard: genome editing our livestock" |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | A talk on genome editing and it's potential impact on livestock breeding was presented to the general public at the British Science Festival in Hull in 2018. Around 50-100 people attended the talk. Publicity around the event, including blogging, press releases etc. reached a much larger public. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.britishsciencefestival.org/event/from-lab-to-farmyard-genome-editing-our-livestock/ |
| Description | How gene editing can contribute to the future of food production, Future of Food and Agriculture, New Scientist Live |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | A panel discussion and interaction through questions of the public on the future of genome-edited animals in the food sector and in the worldwide development of agriculture. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Invited Speaker - 33rd ENGL Plenary Meeting - European Commission |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Presentation on novel breeding technologies in animals and how advances can help us face global challenges. Attendees from the European Commission, Ministries from European member states, researchers and the overall audience showed a keen interest in the advances recently made in the animal biotechnology sectors. There is a clear interest in regulating and thereby opening the pathway to integration of novel breeding technologies from member states. The discussion was very engaged and has since lead to more specific interactions with the ministries of individual member states. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Invited Talk at the Wellcome Animal Genetics and Diseases conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | As part of the Wellcome Animal Genetics and Diseases conference I presented our and other peoples work on genome editing for disease resistance and production traits in livestock. The audience was a conglomerate of national and international scientists at all career stages and highly engaged in debating both scientific as well as policy questions surrounding genome editing technology. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited participation - 2nd Albrecht Mueller ARRIGE Seminar |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Important discussion around the Social and Ethical Implications of Genome Editing in Animals. Particularly impactful in the context of the Genetic Technology (Precision Breeding) bill in the UK and linked responses from interested parties. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.arrige.org/portfolio/2nd-albrecht-muller-arrige-seminar/ |
| Description | Invited presentation - 4th International Workshop on Regulatory Approaches for Agricultural Applications of Animal Biotechnologies |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Workshop discussions on international trade and regulation of novel breeding technologies in animal biotechnology. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Invited round table lead World Vaccine Congress 2018, Lisbon |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | In a session looking out to new developments in the world-wide vaccine sector I was asked to lead a round table on genome editing (for disease resistance) in livestock and how that may affect the sector but also whether the biopharma industry should invest in genome editing. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Invited speaker Heinrich Pette Institute |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Talk about using genome editing in livestock for disease resistance and why understanding protein interactions is essential to this. The audience were primarily staff and students of the HPI and the university of Hamburg. The institute is highly engaged in structural interaction studies and there was a fruitful discussion on how interdisciplinary collaborations can contribute to the larger picture. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited speaker Production Diseases in Farm Animals, 2019 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Around 200 people attended my talk at the Production Diseases in Farm Animals conference. I presented on genome editing for disease resistance in livestock species, implications on breeding, and the regulatory framework and policies. This sparked a wide and interesting discussion with many follow-up questions primarily from members of industry. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited speaker summer school Leiden University |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | Lecture on genome editing in livestock for production traits and disease resistance, the technology behind it, and the policy changes happening around the world. Around 25 students (both under- and postgraduate) attended the lecture and were engaged in a very broad discussion. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited talk European Veterinary Vaccinology Workshop 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Talk on career opportunities in academia for young scientists |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.youtube.com/watch?v=hTujbImUCcI |
| Description | Invited talk FU Berlin - Genome editing in livestock |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Presentation on genome editing in livestock in general (and the opportunities that creates) as well as specifics on genome editing in pigs for disease resistance. Both fellow scholars from different universities in Berlin as well as undergraduate and postgraduate students were attending the talk. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Invited talk at the Swiss Virology Meeting 2023 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | A talk presenting an overview or our research activities from genome editing, primary cell models (including organoids, iPSCs, primary cells, complex cell models) with a primary focus on genome editing. |
| Year(s) Of Engagement Activity | 2023 |
| URL | http://swissvirology.ch/ |
| Description | Invited talk on Enabling Collaboration in Livestock Research. BBSRC Session. BSAS Annual Conference 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presentation at the annual conference of the British Society of animal Science 2018 on "Gene edited pigs are resistant to PRRSV infection whilst maintaining biological function of the editing target gene CD163" |
| Year(s) Of Engagement Activity | 2018 |
| Description | Keynote Lecture IPRRSS / IPVS 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presentation on "Gene edited pigs are resistant to PRRSV infection whilst maintaining biological function of the editing target gene CD163" at the international PRRSV symposium and the International Pig Veterinary Society meeting 2018 in Chonqing, China. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Lothian Agricultural Discussion Group |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Visit by the Lothian Agricultural Discussion group to the Large Animal Research and Imaging Facility. Primarily from a farming or veterinarian background the audience was engaged in listening to the talks and asking further questions around biotechnology and animal research. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Nuffield Research Placement |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | A Nuffield Research Placement student was hosted in the lab to learn the basics of genome editing. Her work was disseminated to the Nuffield Research Placement students and the students were also shown around the research farm of the Roslin Institute and informed about ongoing animal research. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Panel interview for Chinese media |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Under the framework of the Newton Swine and Poultry Workshop in Beijing, China, a panel interview with selected grant holders of the "UK-China-Philippines-Thailand Swine and Poultry Research Initiative" was held at China Agricultrual University. Chinese and China-based international press was in attendance (amongst others, Reuters) and reported on the initiative, developing new antiviral strategies, diagnostics and on other developments in the pig- and poultry industry in China and related research. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Pirbright Institute Scientific Seminar - Tales of two viruses - Nanopore sequencing, genome editing, and stem cell models for ASFV and PRRSV |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Talk on genome editing for resistance, nanopore sequencing of ASFV and PRRSV. Outcome was the setting up of new collaborations and scientific input. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Presentation to the Slovenian ministries of agriculture, economy, and higher education on genome editing in animals |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | An presentation on the use of new breeding technologies in animals to tackle global challenges. Engaged discussion with the participants on how these technologies can be regulated and integrated in international livestock production. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Press interviews on PRRSV-resistant pigs press release |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | In connection with the publication of our research paper "Pigs Lacking the Scavenger Receptor Cysteine-Rich Domain 5 of CD163 Are Resistant to Porcine Reproductive and Respiratory Syndrome Virus 1 Infection" (doi: 10.1128/JVI.00415-18) numerous press interviews were held and inquiries from the public responded to. Media broadcast interviews (Radio or TV) UK: • BBC Scotland • BBC National • BBC International • BBC Farming Today • BBC Sunday Morning Live Print media interviews UK: • The Guardian • The Times • Veterinary Times • Vet Record • The Scientist International print and broadcast interviews: • Swiss Radio & TV (SRF) • NTN24 (CST Science, Health & Technology Magazine, Latin Americas) • Country Today (Victoria, Australia, Radio) • Country Life (Agricultural Newspaper, BC, Canada) • Agri-Pulse (Agri Newspaper, Washington DC, USA) • Bloomberg / Newsroom (Hong Kong) • Rabobank / Raboworld (The Netherlands / Worldwide, Finance) Requests from the general public / public organisations: • Quality Meat Scotland |
| Year(s) Of Engagement Activity | 2018,2019 |
| Description | Press reports on PRRSV-resistant pigs |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | In connection with the publication of our research paper "Pigs Lacking the Scavenger Receptor Cysteine-Rich Domain 5 of CD163 Are Resistant to Porcine Reproductive and Respiratory Syndrome Virus 1 Infection" (doi: 10.1128/JVI.00415-18) we published a press package and answered interview request from many broadcasting and media agencies. As a result the following print and broadcast pieces were released: International Broadcast: BBC Scotland, BBC News at Six, BBC News at Ten, BBC World, BBC Sunday Morning Live, BBC Radio 4 Farming Today, BBC Radio Five Live, BBC Radio 4, BBC Radio Scotland, BBC World Service, Guardian Podcast, BBC Radio Shetland, Swiss Radio & TV (SRF), Country Today (Victoria, Australia, Radio), Fiji Broadcasting Corporation, France 24 Print UK: The Daily Telegraph, The Times, The Guardian, Scottish Daily Mail, The i, Scottish Daily Express, The Sun, Scottish Sun, Daily Mirror, Daily Star, Metro, The Herald, Scotsman, Daily Record, Dundee Courier, Edinburgh Evening News, Aberdeen Evening Express, The Week, Press & Journal, Yorkshire Post Online UK BBC Online, Daily Telegraph, Daily Mail, The Times, The Guardian, Daily Mirror, Daily Express, Scotsman, Irish News, Irish Examiner, Shropshire Star, Express & Star, Hastings Observer, Scarborough News, Eastbourne Herald, Shoreham Herald, West Sussex County Times, Yorkshire Evening Post, Glasgow South & Eastwood Extra, Rye & Battle Observer, Crawley Observer, Bognor Regis Observer, Mid Sussex Times, Worthing Herald, Littlehampton Gazette, Bexhill-on-Sea Observer, Portsmouth News, Chichester Observer, Midhurst & Petworth Observer, Dundee Evening Telegraph, Aberdeen Evening Express, Independent Recorder, TDNews, BT.com, BreakingNews.ie, The London Economic, The Weekly Observer, The Scientist, The London Economic, Science Magazine, Earth.Com, Independent Recorder, BT.com, Breakingnews.IE, I4U News, Press & Journal, Livekindly.co, Tech Times, IFLScience, Technology Networks Online / Print International: NTN24 (CST Science, Health & Technology Magazine, Latin Americas), Infosurhoy, The Economic Times (India), First Post (India), Eurasia Review, HealthEuropa, Jstor Daily, Times Of India, St Lucia News Online, Times Now (India), Business Standard (India), CanIndia.com (India), Green Report (Italy), New Kerala.com, Fanpage.It (Italy), Le Monde Veterinaire (France) Veterinary / Science-related press: Agri-Pulse, Veterinary Times, Vet Record, Pig World, Feedstuffs, Laboratory Equipment, GlobalMeatNews.com, Animal Pharm, Ag Daily, Agribusiness Intelligence, Laboratory Equipment, Pig Progress, Pig World, Labiotech.EU, MRCVS, Farmweek, National Hog Farmer, Farming UK, Frontline Genomics, Farmers Weekly, Food Weekly News |
| Year(s) Of Engagement Activity | 2018,2019 |
| URL | https://www.ed.ac.uk/roslin/news-events/latest-news/gene-edited-pigs-resistant-billion-dollar-virus |
| Description | Research Insights: Science after Dolly |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Research Insights podcast on Science after Dolly. Interdisciplinary presentation on genome editing (for PRRSV resistance) and the ethics around it. Sparking a good discussion on regulation, dysregulation, and ethics. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.ed.ac.uk/medicine-vet-medicine/news-events/college-events/research-insights/winter-21-22... |
| Description | Seminar on genome editing for PRRSV resistance at CLSU, Munoz, The Philippines |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | Genome editing for disease resistance in livestock in general and in pigs for PRRSV resistance was presented to all veterinary students and other department students at Central Luzon State University in the Philippines. Students could inquire the techniques and developments in this field and assess identify new approaches to disease treatments / prevention in animals. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Talk at the American Society for Virology |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Presentation on "Using precision editing tools and novel pig stem cell technology to generate PRRSV-resistant pigs". Attended primarily by international researchers, but also media, industry, and third sector organisations. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Talk on genome editing at Newcastle University Animal Science Conference 2021 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Undergraduate students |
| Results and Impact | Talk on genome editing at the Newcastle University Animal Science Conference 2021. Fantastic discussion on regulation and great interaction with students on the subject. Great feedback and interest in the area. |
| Year(s) Of Engagement Activity | 2021 |
| Description | The Scotsman Data Conference 2021 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Debate on genome editing, use of data in agriculture and breeding. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Visit by a group of Co-operative managers from Switzerland |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | A group of local area managers from the fenaco group, one of the biggest feed producers and distributers in Switzerland, were visiting the institute to learn about genome editing. Being faced with new breeding technologies they wanted to learn about the advances, the impact, and the future of these technologies in plants and livestock. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Which little piggy? goes to schools |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Within our EBSOC outreach centre we had developed an engagement activity for upper secondary school, called "which little piggy?". This allows school children to learn about genome editing, whilst developing basic techniques, such as PCR and agarose DNA gel electrophoresis. Due to COVID we could not follow our usual engagement activities, such as the Royal Highland or other farm shows, which meant we had to reconsider our engagement program for this grant. As we could also not run our school-engagement courses on site, we decided to develop PCR toolkits that could be sent out to schools with instructions and online education for teachers to perform the activities, such as "which little piggy?" with their pupils. This allowed us to engage, even though remote, with pupils and teachers and engage them in genome editing. |
| Year(s) Of Engagement Activity | 2020,2021 |
| URL | https://www.ed.ac.uk/easter-bush-campus/science-outreach-centre/schools/international/genome-editing... |