Restriction of avian viruses by host interferon-inducible transmembrane proteins (IFITMs).

Lead Research Organisation: The Pirbright Institute
Department Name: Avian Viral Diseases

Abstract

Poultry products are the main source of animal protein for human consumption worldwide. Current global production is 55 billion chickens per year. Global population growth and rising affluence are fuelling demand for poultry meat and eggs, and a need exists to increase their supply. The UK poultry industry contributes around £3.4bn to the UK economy. Viruses that infect poultry create major challenges to animal health through loss of productivity and disease. These have simultaneous effects on the global poultry industry through a reduction in the output of poultry meat and eggs. Birds often carry viruses in the absence of any clinical symptoms; however some types of viruses cause severe diseases in poultry that exert substantial animal welfare and economic costs. Therefore, developing efficient control strategies against these viral diseases is crucial for the poultry industry, but also very important in alleviating poverty in developing countries, where these diseases are widespread, causing devastating effects on poultry farming.

Recent evidence has revealed that a family of proteins produced in human cells is able to limit the entry processes and replication of several very dangerous human viruses. Direct clinical relevance of the involvement of these proteins in viral diseases has recently been shown in patients hospitalized with the seasonal flu viruses. In this study researchers showed that more patients with severe symptoms had a particular version of the protein that is not commonly found in the population. These results reveal that the action of these proteins can profoundly alter the course of flu infections by limiting the spread of virus in the body's cells. Although these proteins have been well characterised in human and mouse, little data exists for other species. To date only limited details of two such proteins have been published in chickens; thought to be equivalent to two of the five known human proteins. No characterisation has been undertakn of the role that these chicken proteins play in the control of avian viruses. Since these proteins appear to be the first line of defence against infection, this suggests that individual chickens or entire poultry flocks with more active versions of the protein may be more resistant to avian influenza virus and other pathogenic poultry viral diseases. The research set out in this proposal will play a fundamental part in explaining how both the gene and protein are linked to viral susceptibility in chickens. Our preliminary work leading to this proposal has established that chickens do indeed have similar version of these proteins, and that they can protect against influenza infection.

It is highly plausible that variation affecting these proteins, as is seen in the human population, explains why some birds are more susceptible to viral infections. By analysing the genetic material of birds that differ in levels of resistance to these viruses, we hope to identify the chicken versions of these proteins that give protection, both in laboratory and commercial chickens. Analysis of these proteins in the chicken presents opportunities not just for a greater understanding of increased viral resistance, but also as tools to combat viruses in the poultry industry. It may be feasible to selectively breed for birds with improved resilience to viral infections; however this requires the identification of resistance-associated factors and knowledge of how they act.

The aim of this proposal is therefore to understand the biology and any genetic changes of these genes in chickens. Specifically we will examine the ability of the genes to protect the chickens against viruses. The output of this project will be in identifying versions of these proteins that give resistance to a number of avian viruses. Poultry breeding companies will then be able to select the protective version of the genes encoding these proteins in all future breeding programmes.

Technical Summary

Recent evidence has revealed that a family of interferon-inducible transmembrane (IFITM) proteins restrict the entry processes and replication of several highly pathogenic human viruses. We have now established that chickens encode functional IFITM3 orthologues that restrict influenza infection in vitro. We hypothesise that certain chIFITM allelic variants confer reduced or enhanced levels of protection to endemic and emerging viruses such as Infectious Bronchitis Virus (IBV), Infectious Bursal Disease Virus (IBDV) and avian influenza virus (AIV). IFITM proteins represent clear opportunities, not just for a greater understanding of enhanced viral resistance, but also as tools to combat these pathogenic viruses in the poultry industry, including viruses with zoonotic potential.

To address the objectives we have set out in this proposal we will answer three main questions:

1. Do chIFITMs restrict diverse avian viral pathogens?
This will define the breadth of antiviral activity of the chicken IFITM locus to important avian pathogens and the consequence on other antiviral genes of altering chIFITM expression levels.

2. What is the level of expression and genetic variation at the IFITM locus within inbred, commercial and outbred broiler and layer breeds?
This analysis will establish within and between breed diversity, and identify rare, potentially protective variants. It should also indicate if selection for production traits in the commercial lines has compromised population susceptibility to avian viral diseases. These markers will also prove useful for any future association analysis at the IFITM locus.

3. To what extent do individual alleles of IFITM genes confer resistance to IAV, IBD and IBDV?
This will characterise the in vivo significance of different chIFITM alleles and provide defined polymorphisms as breeding markers to improve intrinsic resistance to important avian virus pathogens.

Planned Impact

With current global production of 55 billion chickens annually, poultry products are the main source of animal protein for human consumption worldwide. The sustainability of this major food resource is now a global research priority. The UK poultry industry currently contributes around £3.4bn to the economy. Avian viruses, such as avian influenza, Infectious Bursal Disease Virus and Infectious Bronchitis Virus create major challenges to poultry health through loss of productivity and mortality, and have concomitant effects on the global poultry industry through a reduction in the output of poultry meat and eggs. Developing efficient control strategies against these viral diseases will not only of benefit Western societies, but also alleviate poverty in developing countries, where these diseases are widespread, causing devastating effects on poultry farming.

The primary focus of this study will be the academic work necessary to underpin and facilitate a range of benefits for different stakeholders. The discovery of the role of IFITM proteins as broad spectrum, anti-viral agents for avian viruses will provide new insights into innate immunity and potentially novel tools and breading programs with which to counter viral pathogens of poultry. The work will create opportunities for medium term industrial outcomes from this project, and we will formulate plans to engage industry in the project. One of the main beneficiaries of this work will be the livestock industry, and specifically poultry breeding companies. Two of the world leading companies, Aviagen and Cobb-Vantress are partners in this Animal Health Research club and thus results generated by this project has a great potential to benefit their global economic performance, and specifically the economic competitiveness of the UK poultry industry. Worldwide, it is likely that the EU and UK policy makers in Animal Health will have an interest in the results due to the impact that the poultry industry has on food sstainability. Outreach activities will be conducted to ensure that stakeholders benefit directly from the project, by gaining a deeper understanding how we intend to turn this research into practice.

We will have impact on the professional development of the scientists involved in this work. In addition to laboratory- and animal-based training, the staff employed on this project will have access to training courses on scientific methods, technical writing, presentation skills, ethics, and transferable skills courses provided by the Pirbright Institute and WTSI. They will also train new staff members and visitors to perpetuate skills and benefit from working with leading poultry companies during the project. Throughout the project we will utilise e-outreach by providing a description and updates of the project for a lay public through the Pirbright Institute and Sanger websites. IAH will also produce a video describing our work for a general audience that will be released during year one (a basic introduction to the project) and year three (the results of the project and future utility). We will engage with the General Public through the provision of press releases to media outlets at the initiation of the project; to both promote the objectives of BBSRC's Animal Health Research Club, and to explore this area of science in an understandable fashion. Scientists employed during the project will also be encouraged to take part in public engagement. Dr Fife is an active STEM ambassador, which creates opportunities to inspire young people and develop their creativity, problem-solving and employability skills the UK's future competitiveness. Prof Kellam gives science presentations to junior and secondary school children and all researchers will be encouraged to participate in STEM activities including school visits.
 
Description We have established that chickens encode interferon-inducible transmembrane (IFITM) orthologues that restrict influenza infection in vitro. The aim of this proposal is to determine the biology and genetic variation of the IFITM locus in chickens, specifically the ability of IFITM genes and alleles to protect the host against both endemic and emerging avian viruses. The output of this project is to identify alleles that correlate with resistance to a number of avian viruses allowing poultry breeding programs to select the beneficial alleles.

The primary focus of this study will facilitate a range of benefits for different stakeholders. The discovery of the role of IFITM proteins as broad spectrum, anti-viral agents for avian viruses will provide new insights into innate immunity and potentially novel tools and breading programs with which to counter viral pathogens of poultry. The work will create opportunities industrial outcomes from this project, and we will formulate plans to engage industry in the project. One of the main beneficiaries of this work will be the livestock industry, and specifically poultry breeding companies. Two of the world leading companies, Aviagen and Cobb-Vantress are partners in this Animal Health Research club and thus results generated by this project has a great potential to benefit their global economic performance, and specifically the economic competitiveness of the UK poultry industry. Worldwide, it is likely that the EU and UK policy makers in Animal Health will have an interest in the results due to the impact that the poultry industry has on food sustainability. Outreach activities will be conducted to ensure that stakeholders benefit directly from the project, by gaining a deeper understanding how we intend to turn this research into practice.

• We have shown that IFITM1, 2, 3, 5 and 10 are present in the chicken genome and are ISGs
• Unlike mammals, all IFITMs are up-regulated upon infection with viral pathogens
• There is differential up-regulation depending on virus used and cell type infected
• We have shown that IFITM 3 is knocked down when siRNA is transfected into immortalised and primary cells
• We have shown that all the IFITMs are expressed constitutively in all chicken tissues tested
• We have re-sequenced the chicken IFITM locus using multiple sequencing platforms including Pacbio, Miseq, and an Oxford Nanopore MinION™ device.
Next:
• Complete the siRNA panel - choose the most potent siRNA or a combination thereof
• Over-express the IFITMs using an IFITM-HA construct and assess the restriction patterns
• Use the IFITM-HA constructs to characterise IFITM localisation
• Complete time course studies on IBV and IBDV infections
• Use embryonated eggs to assess differences in expression of IFITM
• Assess the impact of differential sex expression of chicken IFITMs
• Use alanine scanning mutants to detect motifs for viral restriction and mode of action
• Work with collaborators in Liverpool to assess Glycosylation & Phosphorylation of IFITMs
• Continue to develop MAbs against IFITM1, 2, 3 and 5 to assess IFITM protein within the cell

Additionally we will examine how multiples viruses respond in the absence of IFITMs, and if the knockdown of these gene has an effect on the transcriptional profile of interferon stimulated genes during infection using an siRNA-based expression system to permanently reduce expression of IFITMs both ex vivo and in vivo.
Exploitation Route This project is ongoing and is providing useful information of the activation of host genes by avian viruses. Vaccine development and avian disease resistance. We are now collaborating with international partners to enable the highest impact for our discoveries and to maximise the output of the IP generated by this project. We have also received additional funding for these activities through our commercial partners in the vaccine and avian genetics industries.
Sectors Agriculture, Food and Drink,Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://www.pirbright.ac.uk/research/GeneticsGenomics/Default.aspx
 
Description The Genetics and Genomics group at the Pirbright Institute have identified these antiviral proteins in the chicken (chIFITM). They have shown that a reduction in chIFITM expression results in an increase in the virus titre in CEFs infected with avian influenza A virus (AIV) H9N2, suggesting that chIFITMs have a functional role in the control of viral infections. The observation may have useful implications in terms of vaccine production. To this end, a patent was filed relating to the modification and testing of avian IFITMs, and has now been granted in multiple countries. Many vaccines have been produced in embryonated hen's eggs or continuous avian cell lines for over 30 years. However, it is well established that the rate determining step in the manufacture of numerous vaccines is the induction of antiviral immune responses that inhibits the replication of vaccine viruses. To generate chIFITM knock-down, we will use cutting edge genetic approaches such CRISPR/Cas9 which will directly target and knock-out chIFITM expression. We believe that this approach will overcome the rate limiting step in vaccine production, directly resulting in increased vaccine yields and improve the speed at which vaccines can be manufactured. We are now collaborating with commercial partners to realise innovation with impact for this discovery. This work has directly led to further funding from the BMGF.
First Year Of Impact 2016
Sector Agriculture, Food and Drink,Communities and Social Services/Policy,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Contributed to Chief Medical Officers report- Genomics section
Geographic Reach Europe 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
URL https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/6310...
 
Description Commercial Partner
Amount £30,000 (GBP)
Organisation HyLine 
Sector Private
Country United States
Start 08/2014 
End 06/2015
 
Description LVIF
Amount $1,500,000 (CAD)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 04/2018 
End 09/2020
 
Description Pathfinder BB/R012431/1 Grant holder: Dr Mark Fife. Grant title: chIFITM knockdown/knockout technology as a platform technology for increased vaccine yields in SPF Eggs.
Amount £12,500 (GBP)
Funding ID BB/R012431/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 11/2017 
End 02/2018
 
Title A Versatile Panel of Reference Gene Assays for the Measurement of Chicken mRNA by Quantitative PCR 
Description Quantitative real-time PCR assays are widely used for the quantification of mRNA within avian experimental samples. Multiple stably-expressed reference genes can be used to control random technical variation between samples. It is necessary to select reference genes with the lowest variation in representative samples. The candidate reference gene assays must be reliable. In particular, they should have high amplification specificity and efficiency, and not produce signals from contaminating DNA. Whilst recent research papers identify specific genes that are stable in particular tissues and experimental treatments, here we describe a panel of ten avian gene primer and probe sets that can be used to identify suitable reference genes in many experimental contexts. The panel was tested with TaqMan and SYBR Green systems in two experimental scenarios, a tissue collection, and virus infection of cultured fibroblasts. GeNorm and NormFinder algorithms were able to select appropriate reference gene sets in each case. We show the effects of using the selected genes on the detection of statistically significant differences in expression. The results are compared with those obtained using 28s ribosomal RNA, the present most widely accepted reference gene in chicken work, identifying circumstances where the use of this gene might provide misleading results. Widely used methods for eliminating DNA contamination of RNA reduced, but did not completely remove, detectable DNA. We therefore attached special importance to testing each qPCR assay for absence of signal using DNA template. 
Type Of Material Technology assay or reagent 
Year Produced 2016 
Provided To Others? Yes  
Impact The assays and analyses developed here provide a useful resource for selecting reference genes for investigations of avian biology. 
 
Title Comprehensive analysis of genetic variants across immune loci in indigenous breeds. 
Description The interferon-induced transmembrane (IFITM) protein family comprises a class of restriction factors widely characterised in humans for their potent antiviral activity. Their biological activity is well documented in several animal species, but their genetic variation and biological mechanism is less well understood, particularly in avian species. Here we report the complete sequence of the domestic chicken Gallus gallus IFITM locus from a wide variety of chicken breeds to examine the detailed pattern of genetic variation of the locus on chromosome 5, including the flanking genes ATHL1 and B4GALNT4. We have generated chIFITM sequences from commercial breeds (supermarket-derived chicken breasts), ancient bone samples, indigenous chickens from Nigeria (Nsukka) and Ethiopia, European breeds and inbred chicken lines from The Pirbright Institute, totalling of 211 chickens. Through mapping of genetic variants to the latest chIFITM consensus sequence our data reveal that the chIFITM locus does not show structural variation in the locus across the populations analysed, despite spanning diverse breeds from different geographic locations. However, single nucleotide variants (SNVs) in functionally important regions of the proteins within certain groups of chickens were detected, in particular the European breeds and indigenous birds from Ethiopia and Nigeria. In addition, we also found that two out of four SNVs located in the chIFITM1 (Ser36 and Arg77) and chIFITM3 (Val103) proteins were simultaneously under positive selection. Together these data suggest that IFITM genetic variation may contribute to the capacities of different chicken populations to resist viral infection. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2019 
Provided To Others? Yes  
Impact This paper is currently in press in. BMC Genomics. 
 
Title IFITM Seq 
Description We have established that chickens encode interferon-inducible transmembrane (IFITM) orthologues that restrict influenza infection in vitro. The aim of our work is to determine the biology and genetic variation of the IFITM locus in chickens, specifically the ability of IFITM genes and alleles to protect the host against both endemic and emerging avian viruses. The output of this project is to identify alleles that correlate with resistance to a number of avian viruses allowing poultry breeding programs to select the beneficial alleles. We have now produced contiguos sequnce for the IFITM Locus that was previously not represented in the Gallus gallus genome. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2016 
Provided To Others? Yes  
Impact We have filed patents for the develpment of vaccines. Patent filed for The Pirbright & Sanger Institutes "Viral resistance genes (IFITM genes) in chickens". International Patent Application No. PCT/GB2014/051693. 
 
Description Horizon Discovery Ltd Cambridge Research Park, United Kingdom 
Organisation Horizon Discovery Group plc
PI Contribution Verify IFITM knock-out cell by qPCR and immuno-blotting. Verification of further knock-out cell lines by DNA sequencing, immuno-blotting and qPCR Cell infection with Avian Influenza Viruses Assess the viral titre of cells infected with Influenza Viruses in K/O and wildtype cells. Quantitative analysis of viral infection in IFITM K/O cells Demonstrate increased AIV viral titres at lab scale and estimation of what this may equate to with respect to vaccine dose yields. Analysis of IFITM K/O cell lines permissivity to a range of additional animal viruses (Relevant to the LVIF). Milestone 7: Demonstrate permissivity increased and viral titres for a range of LVIF relevant viruses in the edited cell lines.
Collaborator Contribution Develop a CRISPR/cas9 gene editing system to specifically target the chIFITM locus in avian cell culture
Impact Grant funding
Start Year 2017
 
Description ILRI Research Collaboration (Kenya, March 2017) 
Organisation International Livestock Research Institute (ILRI)
Country Kenya 
Sector Charity/Non Profit 
PI Contribution Exchange of ideas and samples for indigenous breeds of livestock
Collaborator Contribution Contributed samples for analysis.
Impact Analysis of indigenous breed genomic sequences for Immune function genes.
Start Year 2017
 
Description Industrial partnership-Aviagen 2018 
Organisation Aviagen Group
Country United States 
Sector Private 
PI Contribution We have established a significant industrial partnership with Aviagen group Ltd. The nature of this work remains confidential.
Collaborator Contribution The nature of this work remains confidential.
Impact The nature of this work remains confidential.
Start Year 2018
 
Description Research Collaboration with Nigeria (23rd - 28th January 2017) 
Organisation University of Nigeria
Country Nigeria 
Sector Academic/University 
PI Contribution Analysis of rare breed indigenous chicken in Nigeria.
Collaborator Contribution Helped with sampling and background information of the breed.
Impact Analysis is ongoing.
Start Year 2017
 
Description SANGER IFITM 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution The Pirbright Institute (TPI) is a world leader in research on viral diseases of livestock with a strong track record in translating this research into effective disease control. The Genetics and Genomics group is interested in understanding the genetics and evolution of animal-pathogen interactions, with the strategic aim of improving the control of viral disease outbreaks. The group's main focus involves the study of the genetic basis of avian viral disease resistance. The virus-restricting IFITM proteins are under investigation in this study, thus contributing directly to the BBSRC key strategic priority on Global Food security.
Collaborator Contribution Wellcome Trust Sanger Institute (WTSI) is a world leader in uncovering the genetic basis of disease including infectious disease, providing results that are translated into diagnostics, treatments or therapies that reduce global health burdens. The virus genomics group investigates human pathogenic virus infections and the molecular genetic determinants of disease pathogenesis and transmission including zoonotic virus infections.
Impact S. Smith, M. S. Gibson, R. Wash, F. Ferrara, E. Wright, N. Temperton, P. Kellam, and M. Fife. (2013) Chicken IFITM3 restricts Influenza viruses and Lyssaviruses in vitro. J. Virology. 87, 12957 Benfield C, Smith SE, Wright E, Wash RS, Ferrara F, Temperton NJ, Kellam P. Bat and pig Interferon-Induced Transmembrane Protein 3 restrict cell entry by influenza virus and lyssaviruses. J Gen Virol. 2015 (in press)
Start Year 2014
 
Title Avian cells for improved virus production 
Description Type I interferons protect cells from virus infection through the induction of a group of genes collectively named interferon-stimulated genes (ISGs). Among these interferon stimulated proteins, are the IFITM (interferon-inducible transmembrane) genes which have been shown to restrict the replication of several highly pathogenic human viruses, including severe acute respiratory syndrome (SARS) coronavirus, filoviruses (Marburg virus and Ebola virus), influenza A viruses (IAVs), and flaviviruses (dengue virus). The Genetics and Genomics group have identified these antiviral proteins in the chicken (chIFITM) and have shown that a reduction in chIFITM expression results in an increase in the virus titre in CEFs infected with avian influenza A virus (AIV) H9N2, suggesting that chIFITMs have a functional role in the control of viral infections. The observation may have useful implications in terms of vaccine production. To this end, a patent was filed relating to the modification and testing of avian IFITMs, and has now been granted in multiple countries. Many vaccines have been produced in embryonated hen's eggs or continuous avian cell lines for more than 30 years. However, it is well established that the rate determining step in the manufacture of numerous vaccines is the induction of antiviral immune responses that prevents the replication of vaccine viruses. To generate chIFITM knock-down, we will use cutting edge genetic approaches such as siRNA and a CRISPR/Cas9 system which will directly target and knock-out chIFITM expression. We believe that this approach will overcome the rate limiting step in vaccine production, directly resulting in increased vaccine yields and improve the speed at which vaccines can be manufactured. We are currently in talks with major vaccine producers keen to adopt this internationally patented technology, to advance the field of both animal and human vaccine production. 
IP Reference United States Patent Application No. 14/895,866 
Protection Patent application published
Year Protection Granted 2016
Licensed No
Impact This work has arisen as a result of an Animal Health Research Club grant. Involvement of the commercial sector has been encouraged and applauded by the ARC Steering committee. The IMPACT of this work is potentially very significant, and could provide considerable income to The Pirbright Institute.
 
Title Chicken IFITMs 
Description The present invention provides an avian cell in which the expression or activity of one or more of the following genes, or a homologue thereof: Chicken IFITM1 (SEQ ID No. 1); Chicken IFITM2 (SEQ ID No. 2) and Chicken IFITM3 (SEQ ID No. 3) is reduced. The invention also provides methods for passaging viruses in avian cells, embryos and/or avian cell lines which have reduced expression of one or more IFITM genes and methods which involve investigating the sequence of one or more of the following genes, or a homologue thereof: Chicken IFITM1 (SEQ ID No. 1); Chicken IFITM2 (SEQ ID No. 2) and Chicken IFITM3 (SEQ ID No. 3). 
IP Reference PCT/GB2014/051693 
Protection Patent granted
Year Protection Granted 2018
Licensed Commercial In Confidence
Impact The present invention provides an avian cell in which the expression or activity of one or more of the following genes, or a homologue thereof: Chicken IFITM1 (SEQ ID No. 1); Chicken IFITM2 (SEQ ID No. 2) and Chicken IFITM3 (SEQ ID No. 3) is reduced. The invention also provides methods for passaging viruses in avian cells, embryos and/or avian cell lines which have reduced expression of one or more IFITM genes and methods which involve investigating the sequence of one or more of the following genes, or a homologue thereof: Chicken IFITM1 (SEQ ID No. 1); Chicken IFITM2 (SEQ ID No. 2) and Chicken IFITM3 (SEQ ID No. 3). This patent has enabled us to leverage funding for continued work.
 
Title Viral resistance genes (IFITM genes) in chickens 
Description Viral resistance genes (IFITM genes) in chickens: potential for increased vaccine produciton. 
IP Reference PCT/GB2014/051693 
Protection Patent application published
Year Protection Granted 2014
Licensed No
Impact Viral resistance genes (IFITM genes) in chickens: potential for increased vaccine produciton.
 
Description AB Improving Approaches to Prevent and Control Viral Diseases of Livestock and Poultry 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Batra, A., Maier, H.J., Britton P., Hiscox, J.A., Fife, M.S., 2015. PI3K/AKT signalling during infectious bronchitis virus infection. Food Security: Improving Approaches to Prevent and Control Viral Diseases of Livestock and Poultry, British Council Research Links Workshop, Istanbul, Turkey (Oral presentation)
Year(s) Of Engagement Activity 2015
 
Description AB International Nidovirus Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Batra, A., Maier, H.J., Britton P., Hiscox, J.A., Fife, M.S., 2014. AKT activation during infectious bronchitis virus infection. XIIIth International Nidovirus Symposium, Salamanca, Spain (Poster presentation)
Year(s) Of Engagement Activity 2014
 
Description AB Society of General Microbiology Annual conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Poster presentation. Batra, A., Maier, H.J., Britton, P., Hiscox, J.A., Fife, M.S. AKT activation during infectious bronchitis virus infection. Society of General Microbiology Annual conference, Liverpool, UK
Year(s) Of Engagement Activity 2013,2014,2015
 
Description Chair of organising Committee for Wellcome Trust-Animal Genetics and Diseases 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This meeting brought together specialists working on the interface between genomics, genetic engineering and infectious disease with the aims of improving animal and human health and welfare.

Scientific sessions included:
Genetics of immune responses and disease resistance
Genetically engineered livestock (including genome editing)
Quantitative genetics and epigenetics applied to disease
Epidemiology and pathogen evolution
Bioinformatics, comparative and functional genomics
Precision medicine of animal companions
Year(s) Of Engagement Activity 2017
URL https://coursesandconferences.wellcomegenomecampus.org/events/item.aspx?e=635&dm_i=2SUU,HOGH,4R4AW1,...
 
Description Encouraging women into science and engineering STEM. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact MH Visited Warwick School, Redhill to talk to secondary students about careers in STEM. A very positive outcome and well received.
Year(s) Of Engagement Activity 2018
 
Description Holt School Surrey. Bee meadow & A-level outreach Talk. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I discussed the importance of pollinators for biodiversity and food security with the younger students. I also discussed careers in science with A-Level students. There was good interaction and many questions surrounding both topics.
Year(s) Of Engagement Activity 2018
 
Description Innovate Guildford Outreach (12th March) 
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 With amazing exhibits, activities, workshops, talks and competitions, it's FREE to attend. Explore the four zones: Engineering, One Health, Digital Media and Future Living, experience interactive performances, hear inspiring speakers (including leading gaming pioneer Peter Molyneux and animal health pioneer Professor Nick Bacon) and take in an amazing atmosphere. Theatre, music and comedy will feature through the day, with everything from how technology might have affected Shakespeare's plays to risky recycling and photographic secrets.
Year(s) Of Engagement Activity 2017
URL https://www.guildford.gov.uk/innovateguildford
 
Description Innovate Guildford Outreach (12th March) 
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 Innovate Guildford Outreach (12th March).
Year(s) Of Engagement Activity 2016
 
Description Invited Speaker at Gates Foundation Keystone Meeting Leveraging Genomic Diversity to Promote Animal and Human Health (S5) Meeting Detail November 25 - 29, 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Genomic variation is a driving force of animal and human health, and susceptibility to disease. Yet our knowledge rarely spans human ethnic genomic diversity and genomic variation between animal breeds, limiting their translational impact. This symposium aims to: 1) Highlight translational genomics in humans and animals (clinical medicine and animal breeding for health and productivity; 2) Explore synergies and cross-disciplinary learning; 3) Explore opportunities to leverage genomic diversity to push the current boundaries to translation; and 4) Address translation and affordability in low- and middle-income settings. Large-scale genomics initiatives like Genome England, the US Precision Medicine initiative, and the Human Heredity and Health in African Consortium are providing extraordinarily large data sets to explore useful genotype-phenotype connections. Equivalent initiatives for animal data are starting. This meeting will explore the translation of genomic research in animals and humans, high and low-resourced environments, ethnic diversity, and cultural context. Identifying common strands in animal and human health opens up opportunities for repurposing of ideas and applications, and for finding innovative solutions for translational genomics through cross-boundary communities of practice.
Year(s) Of Engagement Activity 2018
URL http://www.keystonesymposia.org/18S5#utm_source=emaillink&utm_medium=banner&utm_campaign=S5email
 
Description Kingdown School Warminster Wiltshire talk to 6th form students about career in science. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I presented my career path to the students to engage them on STEM careers. I had a good level of discussion and many questions.
Year(s) Of Engagement Activity 2018
 
Description MF AIRG 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Avina immunology research group meeting in Canada
Year(s) Of Engagement Activity 2014
 
Description MF PAG 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Plant and Animal Genome XXIV Conference (PAG) is designed to provide a forum on recent developments and future plans for plant and animal genome projects. Consisting of technical presentations, poster sessions, exhibits and workshops, the conference is an excellent opportunity to exchange ideas and applications on this internationally important project.
Year(s) Of Engagement Activity 2014,2016
 
Description MF STEM2 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 1200 students from Years 9-13 i.e. pre- and in sixth form. Our exhibits included Vero cells in flasks, plaques, Vero cells viewed down a microscope, 2D real-size models of sequencing kit, virus and DNA models, careers hand-outs.
Year(s) Of Engagement Activity 2015
 
Description NL Animal Health Research Club 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact ARC will hold up to two dissemination events per annum. The aim of these events is to facilitate the dissemination of the research findings from the grants awarded through ARC to the Industry Members of the Club and other researchers. The dissemination events also provide an excellent opportunity for networking and we encourage delegates to make the most of the time made available for this purpose in the programme. BBSRC staff and the ARC coordinators will be available throughout the day should you have any questions regarding the Club.
Presentations: The presentations are the main opportunity for ARC research groups to present research findings and future plans and for Industrial Members to find out about ARC funded projects and provide feedback. Featured projects have been allocated presentation time as described in the programme and should include at least 5 minutes for questions. Presenters are asked to keep to time and presentations should demonstrate the relevance of the work to animal health and the livestock industry.
Posters: Research groups funded through ARC have been offered the opportunity to provide posters of work which is of relevance to the Industry Members of the Club. This will provide an opportunity to have informal discussions about current progress during networking activities and provide additional project information of relevance to ARC.
Year(s) Of Engagement Activity 2015,2016
 
Description NL Next Generation Sequencing applications to improve livestock welfare, food security and socioeconomic stability in Brazil, British research Council, Newton Fund 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation: Next Generation Sequencing applications to improve livestock welfare, food security and socioeconomic stability in Brazil, British research Council, Newton Fund
Year(s) Of Engagement Activity 2015
 
Description NL Transcriptomics 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 2nd Transcriptomics Workshop, The Jenner Institute. Oxford, UK. 08/05/2015
Year(s) Of Engagement Activity 2015
 
Description Organiser of the Animal Genetics and Diseases conference 08 - 10 May 2019 Wellcome Genome Campus, UK. Highlighting recent advances in animal genetics and genomic technologies. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I am on the organising committee for this conference. The second conference in this series will highlight recent advances in animal genetics and genomic technologies. It will bring together specialists working on the interface of genomics, genetic engineering and infectious disease with the aims of improving animal and human health and welfare.

Novel genomic technologies, mathematical modelling and quantitative genetics approaches, applied to host animals, as well as their pathogens, have transformed the understanding of animal diseases, host-pathogen interactions and epidemiology and their effects on productivity of farmed animal species and food supply chains.

This year's conference will not only put the spotlight on the immune response of host animals and epidemiology but also cover the genetics and genomics of pathogens and the impact of animal-human relationships.

We encourage registrations from researchers, breeders and technical specialists interested in learning and disseminating the latest cutting-edge techniques and methodologies across model species, wildlife, farmed animals and companion animals.
Year(s) Of Engagement Activity 2019
URL https://coursesandconferences.wellcomegenomecampus.org/our-events/animal-genetics-diseases-2019/?dm_...
 
Description STEM Outreach Event (Farnborough, 9th November) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact See web link
Year(s) Of Engagement Activity 2016
 
Description TW ARC 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact ARC will hold up to two dissemination events per annum. The aim of these events is to facilitate the dissemination of the research findings from the grants awarded through ARC to the Industry Members of the Club and other researchers. The dissemination events also provide an excellent opportunity for networking and we encourage delegates to make the most of the time made available for this purpose in the programme. BBSRC staff and the ARC coordinators will be available throughout the day should you have any questions regarding the Club.
Presentations: The presentations are the main opportunity for ARC research groups to present research findings and future plans and for Industrial Members to find out about ARC funded projects and provide feedback. Featured projects have been allocated presentation time as described in the programme and should include at least 5 minutes for questions. Presenters are asked to keep to time and presentations should demonstrate the relevance of the work to animal health and the livestock industry.
Posters: Research groups funded through ARC have been offered the opportunity to provide posters of work which is of relevance to the Industry Members of the Club. This will provide an opportunity to have informal discussions about current progress during networking activities and provide additional project information of relevance to ARC.
Year(s) Of Engagement Activity 2015,2016
 
Description TW Oxford Interdisciplinary Bioscience Networking Event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Oxford Interdisciplinary Bioscience Networking Event
Year(s) Of Engagement Activity 2015
 
Description TW Society for General Microbiology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Society for General Microbiology 2015 Meeting
Year(s) Of Engagement Activity 2015
 
Description Taiwan -UK Partnering Award: Surveillance of influenza viruses 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Attended the International Flu Virus Symposium for Celebrating IPM 47th Anniversary" in Tri-Service General Hospital in Taipei, Taiwan.

Tri-Service General Hospital address:
No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City 114, Taiwan (R.O.C.)

Invited speaker for medical staff and research scientists.
Year(s) Of Engagement Activity 2019
URL https://www.cdc.gov.tw/rwd/english
 
Description Tillingbourne bug hunt. New Rd, Chilworth, Guildford GU4 8NB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Stimulating increased interest in science and research. Good interest and engagement.
Year(s) Of Engagement Activity 2018
 
Description Winston Churchill Careers Fair. Winston Churchill School, Hermitage Road, St Johns, Woking, Surrey, GU21 8TL 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact AS attended and presented at this event to stimulate increased interest in science and research.
Year(s) Of Engagement Activity 2018