Development and exploitation of animal biotechnologies

Lead Research Organisation: University of Edinburgh
Department Name: The Roslin Institute

Abstract

Genetic modification in the mouse has provided increasingly sophisticated tools for investigating all aspects of development and physiology of this model vertebrate. The Roslin Institute has a strong track record in development and application of genetic modification technologies in farm animal species. These have provided powerful tools to answer fundamental biological questions while at the same time providing the platform for the development of novel commercial opportunities. This theme aims to enhance animal transgenesis through novel stem cell based approaches and direct embryo manipulation methodologies. We will exploit novel strategies for animal stem cell derivation, based on the induction of pluripotent stem cells (iPS cells) by expression of key transcription factors in differentiated cells, as exemplified by Takahashi and Yamanaka. We will develop robust culture protocols for such cells and use them as tools for genetic modification and develop differentiation protocols, for applications in animal production and basic bioscience underpinning animal and human health. In parallel, for poultry, we have established and advanced the culture of chicken primordial germ cells, the precursors of the gametes, which will enable us to develop cell-based methods for genetic modification of poultry. We will develop more sophisticated genetic modification technologies, using these novel cell-based systems and by direct in vivo manipulation, including gene knockout and gene targeting in pigs, sheep, cattle and poultry. These technologies will be applied in a wide range of programmes, in collaborative projects, jointly with other ISPs, external collaborators and industry.

Publications

10 25 50

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Arends MJ (2016) Animal and cellular models of human disease. in The Journal of pathology

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Bruce A (2013) Novel GM animal technologies and their governance. in Transgenic research

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Carlson DF (2012) Efficient TALEN-mediated gene knockout in livestock. in Proceedings of the National Academy of Sciences of the United States of America

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Clinton M (2016) Real-Time Sexing of Chicken Embryos and Compatibility with in ovo Protocols. in Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation

 
Title Photography 
Description Photographs for the new website of The Genetics Society from 2016 to present. 
Type Of Art Image 
Year Produced 2016 
Impact Impact through all members of the Genetics Society, its website and social media. Also, conference photos. see: https://www.research.ed.ac.uk/portal/files/47857104/GS_Conference_DougV.jpg 
URL http://www.genetics.org.uk
 
Title Posters: Chromatin, Epigenetics, and Transcriptional Regulation Meeting - UoE Network 
Description Poster for each meeting since 2014 
Type Of Art Artwork 
Year Produced 2013 
Impact Our network across five campuses (Roslin, IGMM, SCRM/QMRI, KB, BMS) connects more than 150 scientists working on related topics within the UoE, with the aim of promoting a strong research community. Meetings take place three times a year and are an opportunity for students, postdocs and PIs to present their work to a specialised audience for feedback and discussion. The meetings aim to foster dialogue between scientists of all levels and promote collaborations between the Edinburgh labs and Institutes. Network interaction between PIs, postdocs and PhD students will take place at the social after the talks (note to late-comers: HRB card entry is required after 6pm). Please see our posters on the notice boards. 
URL https://www.research.ed.ac.uk/portal/files/52878194/Poster_Douglas_Vernimmen_21_Feb_2018.jpg
 
Title Promotional video for The Genetics Society 
Description Welcome to the Genetics Society! Our Learned Society acts to support and promote research and teaching of genetics in the UK. It covers the study of genomes, genes and gene action, and embraces scales ranging from the molecular and cellular to the population and ecosystem level. 
Type Of Art Film/Video/Animation 
Year Produced 2018 
Impact The Genetics Society runs two scientific meetings a year, and provide funding for undergraduate summer projects, fieldwork, training, specialist interest groups, scientific meeting organisation, conference attendance and travel. We also award a number of named Medals and Prize Lectures to outstanding and distinguished geneticists each year. Our members come both from the UK and overseas: we maintain links with several genetics societies in other countries. Membership is open to anyone with an interest in genetics research or teaching. 
URL https://www.youtube.com/watch?v=AN3RIf2Aydk
 
Description We have generated iPSCs from different large animal species and have demonstrated their ability to differentiate into several cell types that are relevant to important production and health traits in livestock. We have generated bovine iPSCs from multiple animals using an inducible viral expression vector and have successfully differentiated them into mammary-like cells that secrete milk proteins (Cravero et al., 2015). Our studies led to the generation for the first time of functional motorneurons and skeletal myotubes from equine iPSCs, and have continuing similar studies using bovine and porcine iPSCs which will provide in vitro systems to identify genes and genetic variants important for meat production in those species. We have generated an HPRT deficient rat as a model of the human neurological disorder Lesch-Nyhan Disease (Meek et al., 2016). The rats exhibit altered metabolism in the brain and loss of serotonin and dopamine - in line with some of the changes observed in brains of Lesch-Nyhan patients and HPRT deficient mice. In addition we have made the novel finding that female HPRT-deficient rats have reduced fertility, suggesting that engagement of the purine salvage pathway is essential for either oocyte maturation or early preimplantation embryonic development. Vitamin C (ascorbic acid), an essential antioxidant and enzyme cofactor, is a common supplement in media formulations used to maintain pluripotency in human ESCs and aid reprogramming of somatic cells to the pluripotent state. We have shown that vitamin C, but not its stereoisomer D-isoascorbic acid, increases the rate of growth and reduces background differentiation in rat ESC cultures. We also have evidence that vitamin C antagonises differentiation factors activated by Wnt/b-catenin signalling but not the Ras/MAPK pathway. We have determined that a novel ESC variant of the Gab1 signalling protein, which is involved in LIF receptor signalling and highly expressed in rodent stem cells, supports ESC survival and is dependent on membrane localisation of this adaptor protein. As well as using standard homologous recombination methodology to target genes in rat embryonic stem cells (ESCs), we have applied gene editing approaches to increase the efficiency of homology-dependent gene targeting. We used TALEN gene editors to promote homologous recombination and targeting of the rat genes for IAPP, CFTR, and neurotrophin receptor p75NTR. The efficiencies for these experiments ranged between 20-90%, thus greatly simplifying gene targeting protocols in rat ESC. We have also used Cre recombinase excision to modify targeted loci to eliminate selection cassettes and engineer point mutations (CFTR) and floxed exons (p75NTR). From these experiments we have generated transgenic rats carrying constitutive and conditional (floxed) alleles of p75NTR. We find that rats lacking the p75NTR protein through deletion of exon 2 of rat p75NTR are healthy and fertile. We have also generated a cystic fibrosis transmembrane conductance regulator (CFTR) knock-in rat that carries the G551D mutation. The G551D mutation is responsible for around 5% of mutant alleles in patients with cystic fibrosis (CF). These animals are being bred to homozygosity for phenotype characterisation. Using a combination of CRISPR/Cas9 and homology directed-repair in ovine zygotes, we have generated a transgenic sheep that is heterozygous for the G551D mutation. These animals will be bred to homozygosity and their phenotype characterised. Several novel and widely applicable fluorescent reporter transgenic chicken lines have been generated for use in developmental biology and infection studies: ubiquitous TdTomato for transplantation studies; lox-stop-loxGFP for CRE recombinase-activated lineage tracing; splitGFP to trace virus infection by delivery of complementary peptide by viruses that leads to GFP fluorescence in infected cells (utilising the support of the National Avian Research Facility). We have developed methods for efficient gene knockout and gene modification using artificial site-specific nucleases in chicken primordial germ cells. These genetic changes are recovered by injection of the genetically-altered primordial germ cells into host chicken embryos which are then incubated and hatched. When the resulting birds reach sexual maturity a proportion of their offspring carry the genetic change introduced at the chosen locus. We first demonstrated gene editing of primordial germ cells using zinc finger nucleases then produced targeted chickens carrying a knockout of the DDX4 gene using TALENs. We have more recently shown that the CRISPR-cas9 system can be used very efficiently to generate genetically-altered chickens with single nucleotide changes or introduction of specific additional sequences by homologous recombination. The development of these "genome-editing" technologies means that we now have very efficient methods for introduction of precise genetic changes in the chicken that are equivalent to those available in the mouse. We have similarly developed the use of zinc finger nucleases, TALENs and CRISPRs to generate gene targeted mutations and introduced exquisitely specific genetic changes in pigs and sheep. We have developed the technology for injection of zygotes from these species, resulting in high frequency of production of animals carrying heterozygous, double heterozygous and homozygous mutations at targeted loci. These technologies have been demonstrated to be applicable in development of animal models and we have made significant advances, in collaboration with another Roslin Institute BBSRC programme, in developing pigs with the potential for resistance to two major pathogens, African swine fever and porcine reproductive and respiratory virus. A further cross-programme collaboration has modelled the integration of genome editing into animal breeding.
Exploitation Route Our research into aspects of isolation and propagation of embryonic stem cells will inform improvements to protocols for production of, for example, human ESCs. The technologies for derivation, differentiation and genome editing of large animal iPSCs will provide powerful in vitro models for the genetic dissection of important production traits in food production animals and the identification of appropriate intervention targets to increase food production. The technologies for genome editing of farmed animals may be transferred to other species of food production animals. The development of large animal models of human diseases will be utilised by the pharmaceutical industry in development and testing of new treatments. The potential of genome editing to confer valuable genetic traits will be incorporated in animal breeding programmes.
Sectors Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology

 
Description Our work on the role of beta-catenin signalling in regulating the differentiation of rat embryonic stem cells contributed to the rational basis for the titration of the GSK3 inhibition in medium used to propagate naïve human embryonic stem cells. The potential for generating and using large animals of human genetic diseases, using the resources, skills and expertise only available at the Roslin Institute in the UK, is under discussion with potential collaborators and medical research funders. The development of genome edited chickens with mutations that when homozygous lead to production of sterile embryos is under development, with a commercial partner, as a route to production of hosts for recovering breeds from cultured primordial germ cells. The application of genome editing in pigs to develop animals that are resilient/resistant to major pathogens is progressing through cross-programme collaboration and with industry involvement. We have a wide programme in public dialogue relating to the regulatory, policy, animal welfare and public concerns relating to the application of genome engineering technologies in animal breeding. We maintain our commitment to openness in animal research and regularly discuss these technologies in this context.
Sector Agriculture, Food and Drink
Impact Types Policy & public services

 
Description Global Challenges Research Fund Strategy Advisory Group
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL http://www.rcuk.ac.uk/funding/gcrf/sagtor
 
Description Nuffield genome editing project
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
 
Description RSB genome editing
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
 
Description Agri-tech Catalyst
Amount £850,000 (GBP)
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 01/2015 
End 01/2018
 
Description BBSRC EastBio
Amount £90,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2016 
End 12/2019
 
Description CONICYT training grants
Amount £179,600 (GBP)
Organisation National Commission for Scientific and Technological Research (CONICYT) 
Sector Public
Country Chile
Start 01/2017 
End 12/2020
 
Description Chromatin, Epigenetics and Transcriptional Regulation - UoE Network 2018
Amount £1,100 (GBP)
Organisation University of Edinburgh 
Department The Institute for Academic Development (IAD)
Sector Academic/University
Country United Kingdom
Start 11/2017 
End 07/2018
 
Description Coming of Age: The Legacy of Dolly at 20
Amount £5,000 (GBP)
Organisation The Genetics Society 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2016 
End 09/2016
 
Description EastBio
Amount £98,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2015 
End 12/2019
 
Description Fellowship
Amount £129,999 (GBP)
Organisation British Society for Haematology 
Sector Learned Society
Country United Kingdom
Start 09/2013 
End 08/2017
 
Description General Scheme - Bruce Whitelaw - Preparation of reagents for vectorisation of RNA decoy vector into lentivirus vector
Amount £22,126 (GBP)
Funding ID WT 6001354 
Organisation Genus plc 
Sector Private
Country United Kingdom
Start 06/2015 
End 01/2016
 
Description General Scheme - Consortium - Gerry McLachlan for RI - The Development Collaboration (DCA)
Amount £0 (GBP)
Funding ID WH/3897302 
Organisation Boehringer Ingelheim 
Sector Private
Country Germany
Start 08/2018 
End 12/2022
 
Description General Scheme - consortium funding - Gerry McLachlan for RI - Lenti viral gene therapy (RCA)
Amount £0 (GBP)
Funding ID WH/3896880 
Organisation Boehringer Ingelheim 
Sector Private
Country Germany
Start 08/2018 
End 12/2020
 
Description Grants
Amount £250,000 (GBP)
Organisation Horserace Betting Levy Board 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2013 
End 08/2017
 
Description Japan Partnering Award
Amount £25,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2014 
End 10/2018
 
Description Portfolio Awards - Consortium Funding - Gerry McLachlan for RI - Respiratory Gene Therapy Portfolio (RGTP)
Amount £1,472,247 (GBP)
Funding ID WH/3695144 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
End 09/2022
 
Title A sterile surrogate host chicken that can be used to revive cryopreserved chicken breeds 
Description We have developed a genetically modified chicken that can be used to revive cryopreserved chicken breeds. We used precision gene editing tools to produce a chicken with a mutation in the gene DDX4. When bred to homozygosity, the chicken does not produce any eggs. This sterile chicken can be used as a host recipient for the transplantation of oocytes from other breeds of chicken. When stem cells from a rare chicken breed are transplanted into embryos from this chicken, the offspring produced will be from the rare breed of chicken. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2017 
Provided To Others? Yes  
Impact This research has led to a publication in a major scientific journal. Many press articles reported this discovery and reported the positive uses of gene editing technology for preserving rare breeds of chicken. We have communicated these results to our Japanese partner of our Japan Partner Award. This chicken is currently being used tested in an Innovate UK project to develop and resurrect a rare breed of chicken. 
URL https://www.theguardian.com/science/2017/feb/17/sterile-genetically-modified-chickens-protect-rare-b...
 
Title Culturing of chicken stem cells for the cryopreservation of chicken breeds 
Description We have developed serum free culture conditions for propagating the stem cells that make sperm or eggs in chicken. These stem cells are taken from a chicken embryo and cultured in vitro to increase their numbers. These cells can then be cryopreserved safely and indefinitely. At a later time, the cells are introduced into a surrogate host embryo and the offspring from this host bird will come from the introduced cells. Our culture methods allows us to propagate these cells from any breed of chicken. These cells can be stored in liquid nitrogen and used to establish a frozen biobank for poultry breeds. 
Type Of Material Cell line 
Year Produced 2015 
Provided To Others? Yes  
Impact We have communicated this cell culture technology to many research laboratories with the goal that they would be able to replicate our findings and begin to biobank breeds of chicken using cultured stem cells. These laboratories are in Japan, Israel, UAE, Iran, France, Hungary, USA, Germany. We have worked closely through our Japan Partner Award with Dr Tagami's laboratory in Tsukuba so that his researchers could implement our cell culture methodology. 
URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682126/
 
Title In vitro Generation of pig macrophages from stem cells 
Description The generation of functionally active monocytes and macrophages from pluripotent pig stem cells 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? No  
Impact This work may provide an in vitro experimental platform for: - Investigation of the pig innate immune system - Investigation of pig macrophage/pathogen interactions - Functional analysis of genetic variation in pigs 
 
Title Mutant rat carrying a floxed Neurotrophin p75NTR allele 
Description Neurotrophin p75NTR is involved in regulating neuronal survival, stem cells and nociception. Using a TALEN gene editor and homologous recombination we have generated rat embryonic stem cells(ESC) in which we have flanked exon 2 of the rat p75NTR gene with LoxP recombination sites to generate a " floxed" p75NTR allele . We used a correctly targeted rat ESC line to generated a mutant rat that carries the floxed p75NTR allele. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact This is the first description of a floxed p75NTR allele in the rat. When mutant rats carrying the floxed p75NTR allele are bred with rats that express CRE recombinase in a tissue restricted pattern this allows conditional deletion of the p75NTR gene in a tissue specific manner. 
 
Title Neurotrophin p75NTR knock-out rat 
Description Neurotrophin p75NTR is involved in regulating neuronal survival, stem cells and nociception. Using a TALEN gene editor and homologous recombination we have generated rat embryonic stem cells(ESC) in which we have deleted exon 2 of the rat p75NTR gene. Using these targeted rat ESCs we have generated a mutant rat that lacks the p75NTR protein. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact This is the first p75NTR knock-out rat generated using rat ESCs, and deletion of exon 2 appears to generate a complete null allele that should allow researchers to accurately assess the role of p75NTR in neurogenesis, the brain and nocioception. 
 
Title Rex1-EGFP knock-in transgenic rat 
Description We have generated a transgenic rat in which we have knocked-in a EGFP-IRESneo reporter gene into the first exon of the rat rex1 gene. The rex1 gene is highly expressed in undifferentiated embryo stem cells and in some cells within the germ lineage. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact The rex1-EGFP knock-in gene allows the characterisation of the rex1 expression pattern in vivo in the rat. It also allows the identification and purification of rex1 expressing cells from rat tissues, and the induction or maintenance of the undifferentiated stem cell state in reprogrammed rat cells. 
 
Title Rex1-egfp knock-in rat embryonic stem cells 
Description The rex1-EGFP rat embryonic stem cell (ESC) line carries an egfp reporter knocked into the rat rex1 gene. Since rex1 expression is tightly associated with the undifferentiated embryonic stem cell state, the egfp reporter provides a way to monitor the differentiation status in live stem cell cultures, and purify subpopulations of cells from rat ESC cultures. 
Type Of Material Cell line 
Year Produced 2015 
Provided To Others? Yes  
Impact We have used the rex1-egfp reporter to characterise and refine the culture conditions for propagating undifferentiated rat embryonic stem cells. 
 
Title animal iPSCs 
Description My group has generated novel equine and bovine iPSC lines 
Type Of Material Cell line 
Year Produced 2015 
Provided To Others? Yes  
Impact These cell lines have provided a novel tool for modelling disease in animals - our and other labs internationally are currently testing their potential and applicability. 
 
Description Bio-Sourcing goat project 
Organisation BioSourcing SA
PI Contribution Design and testing of gene expression systems in vitro
Collaborator Contribution Resourcing of project
Impact ongoing research
Start Year 2017
 
Description Collaboration with industrial partner: Cobb Europe 
Organisation Cobb Europe
Country United Kingdom 
Sector Private 
PI Contribution This Innovate UK project allowed us to build a collaboration with Cobb Europe. The researchers (PI and postdoctorate researcher) working on the Innovate project communicated monthly with Cobb Europe management. We
Collaborator Contribution We have ongoing conference calls and steering committee meetings to govern the interactions between myself, Cobb Europe, and other researchers and management at the Roslin Institute.
Impact In the first instance, the outputs form this collaboration will be listed under the Innovate grant. Future outputs occurring from our continuing collaboration will be listed here.
Start Year 2015
 
Description Equine iPSCs for disease modelling 
Organisation French National Institute of Agricultural Research
Country France 
Sector Public 
PI Contribution Provided equine iPSCs
Collaborator Contribution Establish potential of equine iPSCs for disease modelling
Impact None yet
Start Year 2016
 
Description Evaluation and validation of membraneGFP transgenic embryos for in vivo imaging 
Organisation University of Dundee
Department School of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We developed a lentiviral vector to deliver a transgene designed to express membrane-localised Green Fluorescent Protein (GFP) ubiquitously in chicken embryos. We generated a transgenic line carrying this vector and provided chicken embryos to the Weijer lab for them to evaluate and develop in vivo imaging technologies.
Collaborator Contribution The Weijer lab advised on transgene design and developed in vivo imaging using light sheet microscopy.
Impact This collaboration lead to a publication Rozbiki et al. (2015) Nature Cell Biology 17, 397-408 and the use of this research tool in the Weijer lab is ongoing, funded by new grants.
Start Year 2012
 
Description Evaluation of Notch-reporter transgenic embryos 
Organisation École Normale Supérieure, Paris
Department Institute of Biology
Country France 
Sector Academic/University 
PI Contribution We developed a line of transgenic chickens carrying a transgene that would express green fluorescent protein as a reporter of notch signalling activity.
Collaborator Contribution The partners utilised embryos from this line to exemplify its utility in experiments to understand vertebrate embryo development.
Impact A paper has been published.
Start Year 2016
 
Description Influenza resistant livestock 
Organisation University of Maryland
Country United States 
Sector Academic/University 
PI Contribution Design and testing of constructs targeting influenza virus
Collaborator Contribution Project implementation
Impact Constructs and animals
Start Year 2016
 
Description Mammary cells from bovine iPSCs 
Organisation University of Turin
Department Molecular Imaging Center
Country Italy 
Sector Academic/University 
PI Contribution Hosted an italian PhD student for 6 months to generate bovine iPSCs
Collaborator Contribution Provided PhD student Differentiated bovine iPSCs (generated at Roslin) into mammary-like cells Led manuscript preparation
Impact Generation of Induced Pluripotent Stem Cells from Bovine Epithelial Cells and Partial Redirection Toward a Mammary Phenotype In Vitro. Cravero D, Martignani E, Miretti S, Accornero P, Pauciullo A, Sharma R, Donadeu FX, Baratta M. Cell Reprogram. 2015 Jun;17(3):211-20. doi: 10.1089/cell.2014.0087.
Start Year 2011
 
Description Pig breeding with Genus 
Organisation Genus plc
Country United Kingdom 
Sector Private 
PI Contribution Developed and demonstrated gene editing in pig zygotes.
Collaborator Contribution Supply of animal resources and funds.
Impact Several publications, presentations at scientific meetings, media opportunities and joint research grants.
Start Year 2010
 
Description Purification technologies 
Organisation Centre for Process Innovation (CPI)
Country United Kingdom 
Sector Private 
PI Contribution We developed lab scale purification of recombinant proteins from the eggs of transgenic hens.
Collaborator Contribution Working with the CPI we have developed a scalable purification process, yielding high quality, pure and biologically active recombinant protein.
Impact Outcomes will be described in publications in 2018.
Start Year 2015
 
Description Surrogate Sires 
Organisation Genus plc
Country United Kingdom 
Sector Private 
PI Contribution Design and strategy to produce germless pigs and cattle
Collaborator Contribution Project design and implementation
Impact publication and patents
Start Year 2015
 
Description Surrogate Sires 
Organisation Washington State University
Country United States 
Sector Academic/University 
PI Contribution Design and strategy to produce germless pigs and cattle
Collaborator Contribution Project design and implementation
Impact publication and patents
Start Year 2015
 
Description iPSCs for equine cloning 
Organisation National University of San Martin
Country Argentina 
Sector Academic/University 
PI Contribution Provided equine cells for testing
Collaborator Contribution Tested the potential of iPSCs for equine cloning
Impact Manuscript published in 2016
Start Year 2015
 
Title Domain 5 of CD163 for Use in Antiviral Compositions Against PRRS and Transgenic Animals 
Description Animals resistant to PRRSV 
IP Reference WO2015011483 
Protection Patent application published
Year Protection Granted 2014
Licensed Commercial In Confidence
Impact scientific publications
 
Title Gene edited pigs with altered RelA activity 
Description production of pigs with altered NFkB activity 
IP Reference EP1216564.3 
Protection Patent application published
Year Protection Granted 2012
Licensed Commercial In Confidence
Impact scientific publications and research funds
 
Title Genetically modified animals and methods for making the same. 
Description Production of pigs with altered RELA 
IP Reference WO2012116274 
Protection Patent application published
Year Protection Granted 2012
Licensed Commercial In Confidence
Impact scientific publications and research funding - media coverage
 
Title Nanos knock-out that ablates germline cells 
Description Animals that lack spermatogonial cells as recipient for SSCs 
IP Reference WO2016011029 
Protection Patent application published
Year Protection Granted 2015
Licensed Commercial In Confidence
Impact scientific publication
 
Title Use of transgenic techniques to manipulate sex ratio or progeny 
Description Using genetic engineering to alter sex ration of offspring in farm breeding 
IP Reference US61/971,869 
Protection Patent application published
Year Protection Granted 2014
Licensed Commercial In Confidence
Impact research funds
 
Title genetically edited swine 
Description production of animals resistant to ASFV 
IP Reference WO2017055844 
Protection Patent application published
Year Protection Granted 2015
Licensed Commercial In Confidence
Impact scientific publications and research grants
 
Company Name ROSLIN TECHNOLOGIES LIMITED 
Description Roslin Technologies is an agriculture biotechnology company that has been established as the commercialisation arm of the world renowned Roslin Institute and University of Edinburgh's Royal (Dick) School of Veterinary Studies. As well as developing a range of new products, we offer a strong platform for industry engagement through a range of services, licencing and collaboration opportunities. Located at the University's Easter Bush Campus which is part of the Midlothian Science Zone, Roslin Technologies is well placed to play a leading role in delivering strong industry impacts from new developments in Agri-tech. Although still rapidly developing, the Zone is already one of the largest animal science innovation hubs in the world, being home also to a number of organisations with animal science expertise and an international reputation for conducting world class research and teaching. Roslin Technologies is a joint venture that builds upon a strong and novel partnership between the world leading research, knowledge and expertise that is contained within the University of Edinburgh, and two investment and business development partners with a strong global network and reach. 
Year Established 2016 
Impact Roslin Technology (commercial partner of Roslin Institute) is currently offering a commercial biobanking service to the poultry industry to biobank commercial chicken flocks using the technology partially developed in this grant. The commercial partner of this grant, Cobb Vantress, Inc, has granted Roslin Technology the right to commercially exploit the non-patentable IP from this project and has made use of this commercial biobanking service offered by Roslin Technology. I, Mike McGrew, am a consultant for the commercial biobanking service.
Website http://roslintech.com/avian-germline-cryopreservation/
 
Description 2 Day Mini Science Festival for Primary Schools: Eastgate Theatre, Peebles 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Primary school children from P3-P7 from 4 primary schools attended workshops on "Brilliant Biology" activities involving DNA extraction from strawberries, personalised model chromosome building to reflect individual traits such as hair colour, eye colour, and a lung biology activity.
Year(s) Of Engagement Activity 2015,2016,2017,2018
 
Description 2nd Edinburgh Rat Genetics Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Stimulate interactions between local scientists, to share data and resources
Year(s) Of Engagement Activity 2017
 
Description BBC Country File interview 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact TV interview on genetically engineered pigs on mainstream BBC Country File programme
Year(s) Of Engagement Activity 2013
 
Description BBC at the Edinburgh Festivals: The Human Body. Lung Biology activity 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Lung biology activity
Year(s) Of Engagement Activity 2017
 
Description Brainstorming workshop on somatic cell derived bovine gametes/embryos 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Brainstorming Workshop on Somatic Cell derived Bovine Gametes/Embryos
Attended by heads of Indian organisations NDDB, DBT, the company TAG, and international research scientists (New Delhi, 25-26th June 2018)
Presented talk entitled " Pluripotent stem cells: Achievements and Challenges"
Year(s) Of Engagement Activity 2018
 
Description British Science Association, Science Week Public Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Public lecture on Cystic Fibrosis Gene Therapy
Year(s) Of Engagement Activity 2016
 
Description British Society for Gene and Cell Therapy. Public Engagement Day. 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Lung Biology, Cystic Fibrosis and Gene Therapy activity.
Year(s) Of Engagement Activity 2015
 
Description Cabaret of Dangerous Ideas: Dolly the Sheep: major discovery or minor distraction? Presenter, Edinburgh Festival Fringe. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Presentation with two colleagues, one a stem cell biologist and one a histrian of science in society, discussing the impact on research and society of the birth of Dolly the Sheep 20 years ago. Potential of GM technologies to confer resistance to diseases in farmed animals was discussed. Plenty of opportunity for audience contributions to debate.
Year(s) Of Engagement Activity 2016
URL http://www.youtube.com/watch?v=LClmL5C9YJE&feature=youtu.be
 
Description Come Dine With The Future 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact What will we be eating in 50 years time? H Sang and 4 other presenters described what will be on their dinner menu, considering advances in technology and challenges of sustainability
Year(s) Of Engagement Activity 2016
URL http://www.youtube.com/watch?v=Bkta-s7z9DY
 
Description Costing the Earth 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact BBC radio interview on genetically engineered livestock for BBC Radio 4 Costing the Earcth
Year(s) Of Engagement Activity 2013
 
Description CropTec 2016: Hopes for the future - New breeding technologies 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Described the basics of gene editing technologies, illustrated with examples of the potential of the technology in agriculture, discussed the challenges of applying the technologies.
Year(s) Of Engagement Activity 2016
URL http://www.croptecshow.com/index.php
 
Description Cutting edge Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Talk on genome edited livestock at international science festival
Year(s) Of Engagement Activity 2016
 
Description DBT workshop 
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 Indian Department of Biotechnology workshop on GM Livestock in Bangalore
Year(s) Of Engagement Activity 2016
 
Description Dolly at 20 
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 Presentation of research work to interested members of the public
Year(s) Of Engagement Activity 2016
 
Description Dolly at 20 
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 Graphic display of research work to audience at Dolly at 20 event
Year(s) Of Engagement Activity 2016
 
Description Edinburgh Rat Genetics Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact A number of laboratories in Edinburgh are using genetically engineered rats to study interesting areas of biology. The purpose of this first workshop was to present interesting new data on using rats as an experimental model, to share technology, resources and experiences amongst our local colleagues - and hopefully provide a forum for developing new ideas and collaborations. Presentations were made by researchers across the university (Roslin Institute, Medical School, IGMM, SCRM and Centre for Integrative Physiology).
Based on this initial workshop, there was interest amongst the attendees to have another meeting in 6-months time, to discuss the applications of CRISPR/Cas gene editing technology and invite a keynote speaker.

The programme of this workshop was organised by the Burdon laboratory

Edinburgh Rat Genetics Workshop - December 1st Roslin Institute (Room B006)
Programme:
9.30-9.45 Tom Burdon Welcome and summary of progress using Rat ESCs
9.45-10.30 John Mullins Introduction to transgenesis in rat, and utility in studying Cardiovascular Biology
Robert Menzies Cardiovascular studies in transgenic rats
10.30 -11.00 Phil Coan Hypertensive rat models
Break for coffee - 11.00-11.30
11.30-12.00 Richard Meehan Chromatin and Methylation in the rat
12.00- 12.30 Peter Kind Fragile X syndrome/Autism rat models
12.30 -13.00 Tilo Kunath Parkinsons disease rat model
Year(s) Of Engagement Activity 2016
URL http://www.roslin.ed.ac.uk/events/edinburgh-rat-genetics-workshop/
 
Description Edinburgh-Tsukuba Symposium: Stem cells and regenerative medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented talk at Symposium entitled " Tuning Self-renewal in rat ESCs" on April 16th 2018 at Tsukuba Medical Research Institute, Japan.
Promoted collaborative discussions.
Year(s) Of Engagement Activity 2018
 
Description Eurostemcell publication 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Online article
Year(s) Of Engagement Activity 2015
 
Description Exploiting the genome: How far can we go? 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Curiosity is part of human nature. We learn from experience and when the knowledge is acquired, we try to exploit it, for good...or evil!

In 1953, Watson and Crick revealed the structure of DNA and fifty years later the entire human genome was sequenced. Since then we have sequenced the genomes of over 10 other species and many more are on their way to being completed. Together with the power of molecular cloning technology, it is now possible to genetically modify organisms with a particular purpose, such as increasing resistance to a particular disease, or to generate new bio-products.

This public lecture was organised by the British Science Association.
Year(s) Of Engagement Activity 2014
URL https://www.youtube.com/watch?v=mCSj5lTslbU
 
Description Flutterby Fundraisers annual "The Big Night Oot for CF" Charity Ball. Presentation entitled : Progress towards Gene Therapy for CF 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Delivered a Research Update at an Annual fundraising ball for a charity that supports our CF Gene Therapy research
Year(s) Of Engagement Activity 2017
 
Description Genome Editing and the Future of Farming 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact On the 6th September The Roslin Institute opened its doors to an array of delegates from the worlds of research, industry and policy to discuss genome editing and its role in the future of farming, with many international colleagues including from USDA and OECD.
The global challenge of food security is time critical as we will need to produce 70% more food by 2050 without destroying the environment. Innovations in food production techniques are urgently required. Editing the genomes of crops and livestock offers new possibilities to address this complex issue. The meeting discussed the status of the technologies in crops and farmed animals and the associated regualtory and societal challenges were debated, lead by presenters with a broad array of relevant expertise. My role was as chair of a session.
Year(s) Of Engagement Activity 2016
URL http://www.nib.ac.uk/reporting-on-the-first-nib-specialist-meeting-genome-editing-and-the-future-of-...
 
Description Glasgow Skeptics: open meeting in Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact "Would you eat a GM chicken?" A presentation about GM farm animals with a focus on flu resistance via GM, plenty of discussion after the talk.
Year(s) Of Engagement Activity 2014
 
Description Hendrix Genetcic workshop 
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 Closed industry workshop on application of genetic engineering technology
Year(s) Of Engagement Activity 2016
 
Description International ITU Mol Biol & Genetics Congress, Istanbul 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact An international congress for undergraduate students. ~300 participants.
Year(s) Of Engagement Activity 2017
URL http://www.mbgkongre.itu.edu.tr/
 
Description Interview for national news, Financial Times 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact "Are these the chickens of the future?"article by science journalist that coordinated to include interviews with myself on GM, Dr Ian Dunn on behaviour and welfare and Dr John Hickey on breeding genetics. This article brought together key aspects of the application of research to poultry breeding and production.
Year(s) Of Engagement Activity 2016
URL https://www.ft.com/content/863e034e-d5c8-11e5-829b-8564e7528e54
 
Description Jedburgh Grammar: CF Gene Therapy Lecture to Higher/Advanced Higher Biology Pupils 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Presentation about genetic mutations, genotypes & phenotypes and advances in gene therapy for CF
Year(s) Of Engagement Activity 2015,2016,2017,2018
 
Description Member of organising committee for symposium " Coming of Age:The Legacy of Dolly at 20" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I was a member of the committee that organised a Symposium celebrating of the legacy of cloning of Dolly the sheep at the Roslin Institute - the first cloned mammal from an adult somatic cells. The whole event consisted of a public lecture by Sir Ian Wilmut (https://media.ed.ac.uk/channel/Dolly%20at%2020%20Public%20Lecture/52163171) followed by a one-day symposium at which many internationally reknown scientist presented their work in the area of cloning and stem cells. The symposium was nationally advertised and open to all academics, but additionally was organised so that students were encouraged to attend, at reduced rates with the support of the genetics society.
Year(s) Of Engagement Activity 2016
URL http://dolly.roslin.ed.ac.uk/events-archive/symposium/
 
Description Midlorthian Science Festival Debate 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Constructive and lengthy debate

Invited back to next festival
Year(s) Of Engagement Activity 2014
 
Description Mini Symposium on pluripotent stem cells 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Attendance at a Mini symposium, held at Kumamoto University - Institute of Molecular Embryology and Genetics.
Presented talk entitled " A beta adaptor for stem cell survival"
Year(s) Of Engagement Activity 2018
 
Description NERC Public Engagement Strategy information event "Public engagement: discussing GM animals" 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented on "Public engagement: discussing GM animals" to illustrate the benefits, interest and challenges of public engagement on a potentailly controversial topic
Year(s) Of Engagement Activity 2016
 
Description News artcile on BBC news website 
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 A press release was developed relating to our publication in BMC Biotechnology describing production and purification of bioactive proteins in the eggs of transgenic hens. This article was written by Pallab Ghosh of BBC and attracted a lot of attention and other news articles across the world. Contacts have been received from interested businesses.
Year(s) Of Engagement Activity 2019
URL https://www.bbc.co.uk/news/uk-scotland-47022070
 
Description Nuffield Council bioethics workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Workshop exploring bioethics of genome editing technology and applications
Year(s) Of Engagement Activity 2015,2016
 
Description Our Changing World Series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact University of Edinburgh showcase lecture on genome editing animals for food security
Year(s) Of Engagement Activity 2016
 
Description Peebles High School Careers Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Sessions with individual or groups of pupils interested in careers in science. Advice on subject choices, degree programmes and shared my own experience in terms of pathways to current position.
Year(s) Of Engagement Activity 2013,2014,2015,2016,2017
 
Description Press release 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Advertisement of research finding through national newspaper and TV
Year(s) Of Engagement Activity 2014
 
Description Published article received press coverage 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Published article discussed in public online forum
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-39006713
 
Description Published article receiving press coverage 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Press article in the Telegraph describing biobanking of chicken breeds using GM chicken hosts in a positive light
Year(s) Of Engagement Activity 2017
URL http://www.telegraph.co.uk/news/2017/02/17/rarechickensbrought-back-brink-extinction-edinburgh-unive...
 
Description Published article receiving press coverage 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Press article on gene targeted chicken used to study germ cell development and to develop surrogate host chickens for rare breed conservation
Year(s) Of Engagement Activity 2017
URL https://www.ft.com/content/10000b26-f52c-11e6-8758-6876151821a6
 
Description RSB Teachers Annual Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Talk on genome editing to teachers conference
Year(s) Of Engagement Activity 2016
 
Description Royal Highland Show: Flu-fighters and Genetic Toolbox activity 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Genetic Toolbox activity on genome editing of farm animals
Year(s) Of Engagement Activity 2017
 
Description SUSS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Talk on impact of genome editing technology on society at annual Scottish universities science school.
Year(s) Of Engagement Activity 2018
 
Description Talk Science at the British Library 
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 and discussion "Biotech on the farm - food for thought?", with a live audience in central London and video avaliable watched<500 times. Audience asked interesting and challenging questions. It was clear that GM as such was not seen by many as a problem as there was more concern about the involvement of multinational companies in food production.
Year(s) Of Engagement Activity 2014
URL https://www.youtube.com/watch?v=KgYIiMM5Z_w
 
Description TedX Glasgow "Why do we need GM chickens?" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact TedX Glasgow is a volunteer-run event attended by a an audience from school children to people supported by their employers to attend for personal development. The talks are very varied addressing a wide range of topics and so this was an opportunity to talk about GM technology in a Scottish context and in the context of sustainable agriculture. There was an oportunity at the end of the day to meet members of the audience freely and I had a lot of interesting discussions. The Youtube video has ~1390 views. https://www.youtube.com/watch?v=DUbqrh5otWs
Year(s) Of Engagement Activity 2017
URL https://www.youtube.com/watch?v=DUbqrh5otWs
 
Description The Food Chain 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact BBC World Service radio interview on genetically engineered livestock for The Food Chain
Year(s) Of Engagement Activity 2018
 
Description editorial on uses of GM 
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 Media (as a channel to the public)
Results and Impact Presented to reporters at AAAS, Boston USA
Year(s) Of Engagement Activity 2017
 
Description named biotechnology speaker on US Ste |Department Economic Bureau Outreach Fund 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact International workshop top engage stakeholders in genetic engineering technology and applications
Year(s) Of Engagement Activity 2015