Developing Rapid Responses to Emerging Virus Infections of Poultry (DRREVIP)

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

The study of viruses of poultry made important contributions to the development of the modern science of virology, due to the ready availability of infectious materials and experimental subjects and by the fact that the majority of the poultry viruses posed no threat to humans. Subsequently the same factors allowed development of techniques for the assay and propagation of viruses in the laboratory, using eggs then tissue culture. These same techniques then played important roles in mammalian virology. Nowadays poultry virology helps protect us from emerging zoonotic viruses such as H5N1 and West Nile virus. It also helps protect the supply of the most important and universally acceptable sources of animal protein to feed a growing world population. That supply has to be protected throughout the sophisticated modern industry, from elite founder stocks in worldwide (including UK and European) breeder companies right down to the massive, obvious level of broiler and egg production. Infectious threats arise regularly, sometimes from previously unknown viruses.
Less obviously, poultry virology plays major roles in human health and in the Biotechnology and Pharmaceutical industries. Isolation and diagnosis of viruses is often conducted in eggs or avian cells, and some important vaccines (notably seasonal and pandemic influenza vaccines) are produced in them. Diagnosis and isolation of viruses that remain unknown, and their production to make new vaccines, will probably require the development of genetically modified eggs and chicken cells.
The UK has traditionally been strong in poultry virus research, arguably leading to the development of the influenza vaccine and to the discovery of antiviral interferon. It has also contributed extensively to work on emerging viruses. BBSRC plans increased effort in poultry virology in the new National Centre for Livestock Virology at IAH Pirbright, working alongside a new National Avian Research Facility at Roslin, Edinburgh. However, until those facilities are completed, the field faces difficulties in recruitment, retention, succession and critical mass.
This proposal addresses important scientific challenges in the design and development of modified cells to allow better isolation and diagnosis of emerging viruses as well as faster and better production of vaccines against them (to protect global food supply but also to benefit the Biotechnology and Pharmaceutical industries). It will cover endemic and exotic viruses as, in the poultry sector, new viruses rapidly cross national and continental boundaries to become global problems.
More importantly, it will help secure effective capacity in UK poultry virus research in advance of the new facilities. It establishes a small, focussed and focal network of university teams, with considerable experience of poultry virology, to recruit young post-doctoral scientists. It will be supported by a leading, representative researcher each from Roslin and IAH, offering network access to those facilities and assisting in managing the programme. Recruits will be trained in the demands of the academic sector, alongside and in collaboration with biomedical scientists, to publish in high impact journals and regularly aim for academic fellowships, yet they will receive strong guidance in poultry virology (and related disciplines) from their teams and the network, with strong support from the IAH and Roslin. The programme cannot cover all aspects of poultry virology and related disciplines but it is hoped that other centres of excellence with interests in poultry virology (e.g. Edinburgh, Belfast, Liverpool, Warwick, DEFRA's AHVLA) will participate in training and collaborating with those who will form the core of the next generation of UK poultry virologists. At the end, some recruits are expected to join the national poultry research facilities while others will remain in universities, but in strong positions to collaborate with those in the facilities.

Technical Summary

Whether emerging viruses present as clinical or sub-clinical, acute or persistent, affects how far they might spread before they are recognised. In either situation, interactions between the virus and cell will be crucial, as they will dictate whether or not the virus will be able to replicate and whether or not it induces the expression of host responses that might be used as key signals of otherwise inapparent infection.

These interactions will be affected by host genetic factors that influence innate antiviral responses, particularly the "cell-autonomous" or "intrinsic" responses, and by virus countermeasures. Consequently, this programme focuses on:

(i) characterizing innate and intrinsic responses, and the influence of different host genetic backgrounds;
(ii) isolating new substrates for virus diagnosis, analysis and propagation (by modifying cells and by producing transgenic chickens);
(iii) studying interactions between known viruses and the innate/intrinsic responses. MDV, ALV-J, IBDV and CAV are good examples of viruses causing sub-clinical and persistent infections. AIV and Newcastle disease virus (NDV) will also be studied because they have well recognised modulators of the mammalian innate/intrinsic responses that are likely to target the chicken (and other avian) responses in broad, but distinct, ways. If AIV were to return to poultry from mammalian reservoirs to which it has become adapted (rather than from ducks, as is usual) it might also be limited by its altered receptor tropism; and
(iv) streamlining recombinant vaccine development by quickly identifying appropriate epitopes and antigens to incorporate into the vaccine (particularly for pathogens with large genomes) that induce suitable responses across different chicken breeds.

In doing so, the programme will create also a cadre of new generation poultry virologists well trained and equipped to tackle the threat posed to global food security by emerging viruses of poultry.

Planned Impact

Potential beneficiaries of this research would be:

Commercial vaccine producers.
The work, though directly relevant to producers of poultry vaccines will have ramifications for the vaccine industry in the human sector. Benefits of the work, if it leads (directly or indirectly) to improved conventional live, killed, recombinant or subunit vaccines will be across the board: increased food security, wealth creation (vaccine producers, poultry producers), quality-of-life (reducing risk of pandemic flu, protecting supply of poultry meat and eggs - a key source of nutrition worldwide, protecting from infection).

Poultry Breeders.
Breeders will have new approaches and materials for diagnostic of incipient latent infections that might threaten their flocks.

Poultry Farmers.
Farmers will benefit from access to improved recombinant vaccines. Initially this will be via relatively high technology commercial producers. However, improvements in yield could reduce vaccine costs making them more accessible in developing countries and smaller-scale operations.

Replacement, Refinement and Reduction of Animals in Research (3Rs).
Most of the programme aims to improve and develop cell lines to allow more work with viruses and vaccines in vitro. In particular the technology to be developed in Goal 5 should to reduce animal usage and severity of procedures by early elimination of some vaccine candidates using just a few animals without the need for challenge experiments, leaving only the best vaccine candidates to receive the full and careful analysis using challenge experiments.

Publications

10 25 50
 
Description Having now passed its original finish date, we successfully applied for a 9 month no-cost extension for the project. Many of the components of the project are on track for their targets. A key finding in 2016 was the ground-breaking demonstration, reported by Long et al in Nature (Species difference in ANP32A underlies influenza A virus polymerase host restriction. Long, J. et al. Nature, 2016; 529 (7584): 101 DOI: 10.1038/nature16474) of the identity of the gene that limits avian influenza virus replication to avian cells, unless they acquire specific mutations to allow them to replicate in mammalian cells, including human. Humans have the same gene but it is longer in all birds except ratites like the ostrich. Consistent with this discovery is the observation by others that avian influenza H5N1 isolated from ostriches looks just like a virus isolated from humans rather than one from chickens.

The ANP32A work has been progressed by the establishment of a collaboration (with Prof Mike McGrew, Roslin Institute), concentrating on transcriptomic analysis of wt & CRISPR-mutant PGCs and on analysis of their ability to support infection of avian influenza virus and other avian viruses. The work is progressing towards patenting and applications for follow-on funding (with potential impact in pharma and agriculture).

In 2016 we also published a manuscript that constitutes a key resource for the relevant community, describing the chicken interferome (Giotis, ES et al. Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-alpha). Vet Res. (2016) Aug 5;47(1):75. doi: 10.1186/s13567-016-0363-8).

Last year we published a manuscript characterising the innate and IFN responses of the immortalised chicken fibroblast DF-1 cell line relative to primary CEFs. (Giotis, ES et al. Constitutively elevated levels of SOCS1 suppress innate responses in DF-1 immortalised chicken fibroblast cells. Scientific Reports (2017) 7, 17485. doi:10.1038/s41598-017-17730-2. We showed that DF-1 is competent in mounting these responses but that they are "dampened" by high-level, constitutive expression of the regulatory ISG, SOCS1. This helps explain why DF-1 is better able to propagate some (but not all) avian (and other) viruses. We have further disabled the innate and IFN responses in DF-1 (as a model) by expression of the BVDV immunomodulator, Npro. The characteristics of the resulting cell line have been extensively characterised biochemically, virologically and by RNA-seq (C. Ross, S, Giotis, S. Goodbourn, M. Skinner; unpublished).

Last year we also co-authored a publication (Dulwich, K. et al. Differential gene expression in chicken primary B cells infected ex vivo with attenuated and very virulent strains of infectious bursal disease virus (IBDV). J. Gen Virol (2017) 98: 2918-2930, doi: 10.1099/jgv.0.000979) as the result of a new collaboration with Dr Andrew Broadbent's group at The Pirbright Institute, describing a novel substrate for strains of IBDV (notably 'very virulent' strains), which previously could only be propagated in vivo, in chicks or in embryonated eggs.

The study of viruses of poultry made important contributions to the development of the modern science of virology, due to the ready availability of infectious materials and experimental subjects and by the fact that the majority of the poultry viruses posed no threat to humans. Subsequently the same factors allowed development of techniques for the assay and propagation of viruses in the laboratory, using eggs then tissue culture. These same techniques then played important roles in mammalian virology. Nowadays poultry virology helps protect us from emerging zoonotic viruses such as H5N1 and West Nile virus. It also helps protect the supply of the most important and universally acceptable sources of animal protein to feed a growing world population. That supply has to be protected throughout the sophisticated modern industry, from elite founder stocks in worldwide (including UK and European) breeder companies right down to the massive, obvious level of broiler and egg production. Infectious threats arise regularly, sometimes from previously unknown viruses. Less obviously, poultry virology plays major roles in human health and in the Biotechnology and Pharmaceutical industries. Isolation and diagnosis of viruses is often conducted in eggs or avian cells, and some important vaccines (notably seasonal and pandemic influenza vaccines) are produced in them. Diagnosis and isolation of viruses that remain unknown, and their production to make new vaccines, will probably require the development of genetically modified eggs and chicken cells. The UK has traditionally been strong in poultry virus research, arguably leading to the development of the influenza vaccine and to the discovery of antiviral interferon. It has also contributed extensively to work on emerging viruses. BBSRC plans increased effort in poultry virology in the new National Centre for Livestock Virology at IAH Pirbright, working alongside a new National Avian Research Facility at Roslin, Edinburgh. However, until those facilities are completed, the field faces difficulties in recruitment, retention, succession and critical mass. This proposal addresses important scientific challenges in the design and development of modified cells to allow better isolation and diagnosis of emerging viruses as well as faster and better production of vaccines against them (to protect global food supply but also to benefit the Biotechnology and Pharmaceutical industries). It will cover endemic and exotic viruses as, in the poultry sector, new viruses rapidly cross national and continental boundaries to become global problems. More importantly, it will help secure effective capacity in UK poultry virus research in advance of the new facilities. It establishes a small, focussed and focal network of university teams, with considerable experience of poultry virology, to recruit young post-doctoral scientists. It will be supported by a leading, representative researcher each from Roslin and IAH, offering network access to those facilities and assisting in managing the programme. Recruits will be trained in the demands of the academic sector, alongside and in collaboration with biomedical scientists, to publish in high impact journals and regularly aim for academic fellowships, yet they will receive strong guidance in poultry virology (and related disciplines) from their teams and the network, with strong support from the IAH and Roslin. The programme cannot cover all aspects of poultry virology and related disciplines but it is hoped that other centres of excellence with interests in poultry virology (e.g. Edinburgh, Belfast, Liverpool, Warwick, DEFRA's AHVLA) will participate in training and collaborating with those who will form the core of the next generation of UK poultry virologists. At the end, some recruits are expected to join the national poultry research facilities while others will remain in universities, but in strong positions to collaborate with those in the facilities. Extend and develop the scientific base in poultry virus research to maintain capacity pending commissioning of new national facilities. Aims: (1) address recognition of emerging viruses before wide dissemination of inapparent infections; (2) address need to prepare for emergence of new subtypes of avian influenza. Better substrates for production of vaccine viruses from (3) transgenic chickens or (4) designer cell lines; (5) faster identification of antigenic epitopes for recombinant vaccines. GOAL A: To create a cadre of new researchers who will form the core of the next generation of UK poultry virologists. GOAL 1 is the development of systems to recognize the pre-symptomatic presence of novel pathogens. Firstly spontaneously or artificially immortalized cell lines will be isolated from CEFs produced from chickens that differ in their genetic susceptibility to viral pathogens. Transcriptomic and proteomic analysis will be conducted on control and induced, or infected CEFs or cell lines, probing for signatures of altered cellular expression and metabolism, for which rapid assays will be developed to detect 'signatures' in culture or in infected embryonated eggs. These same 'omic approaches will also be applied elsewhere to support the other goals. 1.1 Development of spontaneously or artificially immortalized cell lines for the propagation of chicken pathogens 1.2 Identifying innate immune responses to persistent viruses using transcriptomics and proteomics of infected CEFs and cell lines. 1.3 Identifying innate immunity genes activated by virus infection of eggs 1.4 Development of qPCR macro-array for the detection of infection signatures 1.5 Development of indicator cell lines for the detection of chicken pathogens GOAL 2 (overlapping with generation of cell lines in Goal 1) will be the direct generation of cell lines more permissive to vaccine virus propagation, by expression of viral modulators or cellular regulators of the innate responses. 2.1 Modification of immortalised chicken cell lines to express putative virus and host-encoded antagonists of innate immunity 2.2 Modification of immortalised chicken cell lines with altered expression of cellular innate response genes 2.2(i) Development of a chicken-specific RNAi screening pipeline. 2.2(iii) Derivation of chicken cell lines more permissive to avian viruses. 2.2(iv) Identification of chicken host factors that enhance antiviral responses. GOAL 3 is the identification of viral and host determinants affecting the outcome of infection with AIV, including HPAI subtypes H5 and H7, to assist in evaluation of whether we need prepare for emergence of novel subtypes into poultry. 3.1 Construction of cell lines to investigate host-range factors for influenza virus 3.2 Generation of rg AIV to study the role of NS1. 3.3 Generation of rgAIV encoding GFP to study in vivo tropism in chickens. 3.4 Generation of rg reassortants of pH1N1 and AIV to test chicken infectivity. GOAL 4 will be the production of trangenic chicken lines in which innate immune suppressor genes are induciblyexpressed, to significantly increase the yield of vaccine viruses produced in embryonated eggs, and in CEFs derived from them. 4.1 Virus in vivo dynamics studies. 4.2 "Super-eggs" enhanced vaccine production vehicles. 4.2.1 Construction of inducible expression plasmids for combinations of IIS genes and chicken ST6GAL1. 4.2.2 Construction of transgenic chickens. 4.3 Comparison of yields and isolation efficiency in transgenic eggs. GOAL 5 is the development and evaluation of a new high-throughput method of determining in vivo T cell responses, to assist recombinant vaccine production, starting with IBDV as a model before tackling the large genome of MDV. 5.1 Developing class I and class II pipelines using selected peptides from IBDV 5.2 Validating both peptide pipelines using the genome of IBDV 5.3. Scanning the MDV proteome using overlapping peptide
Exploitation Route The approaches to cell engineering that we are developing will be of use to the veterinary vaccine industry
Sectors Agriculture, Food and Drink,Environment,Government, Democracy and Justice,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://www.sciencedaily.com/releases/2016/01/160106143025.htm
 
Description ChTRIM15 (homologue of human TRIM21) has been identified by Fred Sorgeloos (working with Prof Ian Goodfellow in Cambridge) from a de novo assembly of RNA-seq reads provided from the Skinner laboratory. It allows purification of chicken IgY antibodies, which are increasingly being used by pharma. It is available for licensing (see: https://www.enterprise.cam.ac.uk/reagents/igy-purification-protein & https://ximbio.com/reagent/152742/chicken-igy-precipitating-protein-vector).
First Year Of Impact 2015
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Chair of Health & Safety Executive's (HSE) Scientific Advisory Committee on Genetic Modification (Contained Use) (SACGM(CU)
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL http://webcommunities.hse.gov.uk/connect.ti/SACGM/grouphome
 
Description Contributing to the chapter on Marek's disease for the OIE Terrestrial Manual
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact The contribution to the Terrestrial Manual on the recent advances in the diagnosis and control of Marek's disease will impact on improved and better control of the disease to reduce losses and improved food security
URL http://www.oie.int/
 
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 Invited to address 21-Oct-15 launch of European Academies Science Advisory Council report on Gain of Function: experimental applications relating to potentially pandemic pathogens
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact Addressed 21-Oct-15 launch of European Academies Science Advisory Council report on Gain of Function: experimental applications relating to potentially pandemic pathogens to describe UK & European approach to risk assessment and management of proposed GoF research
URL https://www.easac.eu/fileadmin/PDF_s/reports_statements/Gain_of_Function/EASAC_GOF_Web_complete_cent...
 
Description Member Jenner Vaccine Foundation Board
Geographic Reach National 
Policy Influence Type Participation in a national consultation
URL http://www.jenner.ac.uk/people
 
Description Participation in the Management of the Oxford DTP
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact As part of the Management committee of the Oxford-Pirbright-Oxford Brookes-Diamond doctorate Training Partnership, contributed to the success of the DTP in meeting the objectives, recruitment and review
URL http://www.biodtp.ox.ac.uk/
 
Description Prof Wendy Barclay: Member of Department of Health's New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG)
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact The New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) is an expert committee of the Department of Health (DH), and advises the Chief Medical Officer (CMO) and, through the CMO, to ministers, DH and other Government departments on the threat posed by new and emerging respiratory viruses. It provides scientific risk assessment and mitigation advice on the threat posed by new and emerging respiratory virus threats and on options for their management
URL https://www.gov.uk/government/groups/new-and-emerging-respiratory-virus-threats-advisory-group
 
Description Re-appointed Chair of HSE SACGM(CU) for further 3 years from 1-Nov-17
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL https://webcommunities.hse.gov.uk/connect.ti/SACGM/grouphome
 
Description Royal Society Contact Group on Gene Editing Technologies
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Dissecting the molecular pathways of MDV oncoprotein Meq for understanding pathogenesis and aid vaccine development
Amount £440,000 (GBP)
Funding ID BB/R007896/1  
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2018 
End 03/2021
 
Description India-United Kingdom Bioinformatics Network
Amount £25,000 (GBP)
Funding ID BB/K021362/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 03/2013 
End 02/2018
 
Description Innovations in control of avian infectious diseases for sustainable growth and food security in low and middle income countries
Amount £200,000 (GBP)
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 12/2016 
End 11/2021
 
Description Marek's Disease Virus induced immunosuppression
Amount £395,000 (GBP)
Funding ID BB/LK014262/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 09/2014 
End 09/2017
 
Description NC3Rs Research Grant
Amount £7,740 (GBP)
Funding ID NC/R001138/1 
Organisation National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) 
Sector Private
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 12/2017 
End 11/2019
 
Description Newton Fund
Amount £45,105 (GBP)
Funding ID BB/R012792/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2018 
End 03/2021
 
Description Recombinant MDV vaccine expressing gRNA targeting REV using CRISPR/Cas9 system to prevent MDV and REV infection
Amount ¥120,000 (CNY)
Funding ID SKLVBF201605 
Organisation State Key Laboratory of Veterinary Biotechnology 
Start 01/2016 
End 12/2017
 
Description Role of PML bodies in avian herpesvirus infections: Generating a tool box of reagents to understand innate restriction of virus infection in chicken
Amount £7,000 (GBP)
Organisation The Houghton Trust 
Sector Charity/Non Profit
Country Unknown
Start 10/2016 
End 09/2017
 
Description Small Project Grant
Amount £9,937 (GBP)
Funding ID E Giotis 
Organisation The Houghton Trust 
Sector Charity/Non Profit
Country Unknown
Start 11/2014 
End 10/2015
 
Description Studentship Identification of genetic markers in the haemagglutinin glycoprotein critical for antigenic activity of H9N2
Amount £118,000 (GBP)
Funding ID BBS/E/I/00001759 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2015 
End 09/2019
 
Description UK-China partnership on Global Food Security: Combating avian tumor diseases for sustainable poultry proudction
Amount £382,000 (GBP)
Funding ID BB/R007632/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2018 
End 03/2020
 
Title CRISPR/Cas9-based gene editing of avian herpesvirus vectors to develop novel recombinant vaccines 
Description Development of recombinant herpesvirus vaccines are usually achieved by classical homologous recombination methods. The advent of new genome editing tools has enabled its application on avian herpesvirus vaccine strains to develop new recombinant vaccines potentially capable of expressing protective antigens from multiple pathogens 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? Yes  
Impact The major impact will be in the generation of novel vaccines that can simultaneously protect against multiple avian diseases 
URL http://www.poultryworld.net/Health/Articles/2016/12/Is-GM-technology-the-future-of-poultry-vaccines-...
 
Title ArrayExpress Accession E-MTAB-3711 
Description Affymetrix GeneChip CEF +/- IFN 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact Giotis et al Veterinary Research (2016) 
URL http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3711/
 
Title ArrayExpress Accession E-MTAB-3712 
Description ST Array CEF +/- IFN 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact Giotis et al Vet Res (2016) 
URL http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3712
 
Title CEF IFN RNA-seq RR1 ERA 
Description RNA-seq data deposited to EBI ERA CEF control or treated with recombinant ChIFN1 (biological triplicates) Thank you for your recent submission to the European Nucleotide Archive. Your study accession number is: PRJEB7620. Your secondary study accession number is: ERP008544. Your study title is: Chicken embryo fibroblasts stimulated for innate responses by exogenous ChIFN1. 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact Improvements to annotation of chicken genome Draft manuscript: Submitted to Cytogenetic and Genome Research as part of the Third Report on Chicken Genes and Chromosomes The Avian RNASeq Consortium: a community effort to annotate the chicken genome (Prepared by Jacqueline Smith, Dave Burt and the Avian RNASeq Consortium) Giotis et al Vet Res (2016) 
URL http://www.ebi.ac.uk/ena/data/view/PRJEB7620
 
Title E-MTAB-3643 
Description Affymetrix Chicken Gene 1.0 ST Arrays "The identification of positive chicken factors for influenza polymerase activity" 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Long et al. Nature (2016) 
URL https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3643
 
Title E-MTAB-4028 
Description Microarray: Genome-wide comparison of Chicken Embryo Fibroblasts (CEF) and DF-1 in response to recombinant chicken chIFN-?? and infection with Infectious Bursal Disease Virus (IBDV) 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Available for comparison of transcriptomic changes following infection with different viruses 
URL https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-4028
 
Title E-MTAB-5947 
Description Transcription profiling by array of differential gene expression in chicken primary B cells infected ex vivo with attenuated and very virulent strains of infectious bursal disease virus (IBDV) 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact Infectious bursal disease virus (IBDV) belongs to the family Birnaviridae and is economically important to the poultry industry worldwide. IBDV infects B cells in the bursa of Fabricius (BF), which can cause severe immunosuppression and mortality in young chickens. Earlier studies have shown that strains of IBDV lose their virulence potential after serial passage in non-B lymphoid cells, for reasons that are poorly understood. This study aimed to investigate the gene expression profiles of one cell-culture adapted attenuated IBDV strain (D78) and one very virulent IBDV strain (UK661) in chicken primary B cells cultured ex vivo from the bursa of Fabricius. The viruses were studied in B cells over 48h and their gene expression was initially evaluated with qPCR. The mRNA was isolated from the cells at 18 hours post-infection and screened with Affymetrix microarrays in triplicate. The study included mock controls which were conducted in triplicate. 
URL https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5947/
 
Description Avian Vaccines Malaysian Researchers 
Organisation Putra Malaysia University
Department Department of Pathology
Country Malaysia 
Sector Hospitals 
PI Contribution We have successfully organized a British Council funded workshop on Emerging and Next Generation Vaccine Technologies Against Veterinary Viruses at Institute of Bioscience (IBS), Universiti Putra Malaysia from 01 to 04 August 2016.
Collaborator Contribution Through this partnership, we have applied two research grants to work together in tackling infections in poultry.
Impact Two Funding Applied One Publication Online
Start Year 2016
 
Description Collaboration and Partnership With American Researchers 
Organisation University of Rochester
Department Neuromuscular Disease Center
Country United States of America 
Sector Academic/University 
PI Contribution To establish bases on system biology of avian immunity, collaboration was established with Luis Martinez-Sobrido.
Collaborator Contribution Researcher from Rochester are establishing mouse reporter cell lines and we at Pirbright are generating chicken reporter cell lines to be used for antiviral and virus pathogensis studies.
Impact We have devised the CRISPR/Cas9 strategy and are working to generate knockin cell lines in both institutions.
Start Year 2016
 
Description Collaboration with Harbin Veterinary Research Institute China 
Organisation Chinese Academy of Agricultural Sciences
Department Harbin Veterinary Research Institute (HVRI)
Country China, People's Republic of 
Sector Public 
PI Contribution We had intellectual input in formulating the research programme
Collaborator Contribution The partners visited Pirbright and set up collaborative research plans and signed a memorandum of understanding
Impact Output or outcomes are yet to materialize. But we had one joint publication
Start Year 2014
 
Description Global Alliance for Research on Avian Diseases 
Organisation Global Alliance for Research on Avian Diseases
PI Contribution This alliance led by Pirbright has participation from over 40 countries and comprises of academics and industry professionals. This forum helps in working together, identifies the challenges and opportunities for improved control of avian diseases
Collaborator Contribution Two successful international meetings were organised as part of this alliance, one in London in 2015 and most recent one in Hanoi, Vietnam in January 2018
Impact Organisation of two successful international meetings and development of significant collaborations
Start Year 2015
 
Description Invitation to participate in the Vaccine Innovation Forum 2017 at Shanghai 26-27 April 2017 
Organisation Chinese Academy of Agricultural Sciences
Department Shanghai Veterinary Research Institute
PI Contribution Prof. Nair was invited to participate in the Vaccine Innovation Forum 2017 at Shanghai 26-27 April 2017 to present a talk on 'Novel Vaccine Development for Avian Virus Diseases'. He also participated in the round table discussions on the challenges and opportunities in the vaccines and vaccination sector
Collaborator Contribution Vaccine Innovation Forum will help in expanding the future collaborations and activities of the UK-China Centre of Excellence for Research on Avian Diseases (http://www.uk-china-cerad.org/).
Impact organised joint meeting in China and the UK to discuss on challenges and opportunities
Start Year 2017
 
Description Microbiology Society Focused Meeting 
Organisation Microbiology Society
Country Unknown 
Sector Learned Society 
PI Contribution 1. V Nair presented a talk on 'Marek's disease pathogenesis' at the Focused Meeting 2016: Molecular Biology and Pathogenesis of Avian Viruses organised by Microbiology Society 27 Sep 2016.
Collaborator Contribution Helped to organise Focused Meeting on Molecular Biology and Pathogenesis on Avian Viruses
Impact V Nair invited talk on 'Marek's disease pathogenesis' at the Focused Meeting 2016: Molecular Biology and Pathogenesis of Avian Viruses organised by Microbiology Society 27 Sep 2016.
Start Year 2016
 
Description Partnership with Brazilian Researchers working on avian and bats immunity 
Organisation Animal and Plant Health Agency
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Through Bats and Birds Research Network, we gathered a team of researcher who have interests or working on avian and bats innate immunity. All above-mentioned partners are now active members of the network and contributing significantly.
Collaborator Contribution We have obtained two funding, one from BBSRC and one from British Council to investigate the role of virus induced innate immunity and dynamics of viruses in these hosts. Brazilian participants are mainly responsible to collect samples, based on their extensive field experience and British partners are involved in the analysis and interpretation of the outcome.
Impact Workshop on Birds and Bats at University of Surrey, June 2016 Poultry Health Course at Pirbright Institute, April 2017 Visit of Brazilian and British Partners to laboratory facilities Virtual Meeting to Discuss and Plan the Collaborations Mutual Funding and Research Articles
Start Year 2015
 
Description Partnership with Brazilian Researchers working on avian and bats immunity 
Organisation State University of Campinas
Country Brazil, Federative Republic of 
Sector Academic/University 
PI Contribution Through Bats and Birds Research Network, we gathered a team of researcher who have interests or working on avian and bats innate immunity. All above-mentioned partners are now active members of the network and contributing significantly.
Collaborator Contribution We have obtained two funding, one from BBSRC and one from British Council to investigate the role of virus induced innate immunity and dynamics of viruses in these hosts. Brazilian participants are mainly responsible to collect samples, based on their extensive field experience and British partners are involved in the analysis and interpretation of the outcome.
Impact Workshop on Birds and Bats at University of Surrey, June 2016 Poultry Health Course at Pirbright Institute, April 2017 Visit of Brazilian and British Partners to laboratory facilities Virtual Meeting to Discuss and Plan the Collaborations Mutual Funding and Research Articles
Start Year 2015
 
Description Partnership with Brazilian Researchers working on avian and bats immunity 
Organisation University of Sao Paulo
Department Department of Virology
Country Brazil, Federative Republic of 
Sector Academic/University 
PI Contribution Through Bats and Birds Research Network, we gathered a team of researcher who have interests or working on avian and bats innate immunity. All above-mentioned partners are now active members of the network and contributing significantly.
Collaborator Contribution We have obtained two funding, one from BBSRC and one from British Council to investigate the role of virus induced innate immunity and dynamics of viruses in these hosts. Brazilian participants are mainly responsible to collect samples, based on their extensive field experience and British partners are involved in the analysis and interpretation of the outcome.
Impact Workshop on Birds and Bats at University of Surrey, June 2016 Poultry Health Course at Pirbright Institute, April 2017 Visit of Brazilian and British Partners to laboratory facilities Virtual Meeting to Discuss and Plan the Collaborations Mutual Funding and Research Articles
Start Year 2015
 
Description Partnership with Brazilian Researchers working on avian and bats immunity 
Organisation University of Surrey
Department Surrey Space Centre
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Through Bats and Birds Research Network, we gathered a team of researcher who have interests or working on avian and bats innate immunity. All above-mentioned partners are now active members of the network and contributing significantly.
Collaborator Contribution We have obtained two funding, one from BBSRC and one from British Council to investigate the role of virus induced innate immunity and dynamics of viruses in these hosts. Brazilian participants are mainly responsible to collect samples, based on their extensive field experience and British partners are involved in the analysis and interpretation of the outcome.
Impact Workshop on Birds and Bats at University of Surrey, June 2016 Poultry Health Course at Pirbright Institute, April 2017 Visit of Brazilian and British Partners to laboratory facilities Virtual Meeting to Discuss and Plan the Collaborations Mutual Funding and Research Articles
Start Year 2015
 
Description UK Korea collaboration 
Organisation Seoul National University
Country Korea, Republic of 
Sector Academic/University 
PI Contribution This collaboration has brought in Pirbright Institute's experience in Virology
Collaborator Contribution Partner's experience in genetics and genomics as well as gene editing and transgenic technology
Impact The visits by the Seoul partners to Pirbright and subsequent discussions on research collaboration has initiated a number of projects. This has also led to the award of the Royal Society International Professorship to Prof. Nair and Prof. Jae Yong Han from Seoul National University
Start Year 2015
 
Title Chicken TRIM15 IgY precipitating reagent ZNF777 
Description Chicken IgY binding protein By Frederic Sorgeloos & Ian Goodfellow (University of Cambridge) 
IP Reference  
Protection Protection not required
Year Protection Granted
Licensed Yes
Impact Valuable research tool
 
Description AVIANVIRUSRESEARCH.ORG website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact AvianVirusResearch.org is an initiative of the BBSRC-funded "DRREVIP" sLoLa to provide a home for information and discussions on research into avian viruses (including those that affect poultry), their pathogenesis and their prevention (especially by vaccines).
Year(s) Of Engagement Activity 2016
URL http://avianvirusresearch.org/
 
Description Birds and Bats Workshop (University of Surrey) 
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 It was organised to bring together researchers from Brazil and UK to discuss the current advances in bats and bird immunity and virology
Year(s) Of Engagement Activity 2016
URL http://birdsandbats.net
 
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 Chaired the Poultry Disease group meeting 
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 Poultry Disease group is a forum of veterinary practitioners to discuss the advances in poultry diseases that could be translated from research labs to the farms
Year(s) Of Engagement Activity 2017
 
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 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 Inauguration of the UK-China Centre of Excellence for Research on Avian Diseases (CERAD) and Symposium on Recent Advances in Avian Disease Research 
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 Inauguration of the UK-China Centre of Excellence for Research on Avian Diseases (CERAD) and Symposium on Recent Advances in Avian Disease Research. This was held in Binzhou, Shandong province in China in 2015
Year(s) Of Engagement Activity 2015
 
Description Interview for the magazine Science & Vie (Science & Life, the n°1 science magazine in France) 
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 Interview for an article on genetically modified farm animals resistant to infectious diseases.
Year(s) Of Engagement Activity 2017
 
Description Invitation to give keynote talk on 'Control of avian diseases: Challenges and opportunities' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave the Keynote talk on 'Control of avian diseases: Challenges and opportunities' at this International Symposium organized with an aim to gather international virology experts from both human and veterinary fields to share research experience, update findings and contribute their expertise through presentation and interactive discussion. The topics will cover a wide range of virology research common in both human and animal aspects. In addition, technological platforms such as vaccine development, and novel assays will be emphasized and addressed.
Year(s) Of Engagement Activity 2018
URL http://www.biotec.or.th/virus-symposium2018/index.php
 
Description Invitation to talk at the Vaccine Symposium "Vaccines at different levels of complexity from subunit to whole cell formulations" jointly organised by the Centre of Genomic Regulation (CRG), Radboud UMC and MSD Animal Health, with the support from the MycoSynVac project 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a talk and participated in the discussion on the challenges and research opportunities for innovation in poultry disease control
Year(s) Of Engagement Activity 2017
URL http://www.crg.eu/
 
Description Invited to talk at the International Conference on Building Human and Animal Health Capacities organised by the Jordan University of Science and Technology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Participated in the discussion and talked on 'The recent advances in vaccination-based control of poultry diseases'. The need for increased awareness of the pathogen diversity in the design of vaccines and the opportunities from advances in vaccine technologies were discussed
Year(s) Of Engagement Activity 2017
URL http://www.just.edu.jo/conferences/bhahc/Pages/default.aspx
 
Description Keynote talk at the World Veterinary Poultry Association meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to give the keynote talk on 'Avian tumour viruses: their contribution to our understanding of cancer' at the World Veterinary Poultry Association XXth Congress in Edinburgh
Year(s) Of Engagement Activity 2017
URL http://www.wvpac2017.com/
 
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 Organisation of UK-India Bioinformatics Workshop 
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 The meeting discussed the challenges and opportunities and have decided to come up with a strategy document on working together between UK and India on data-driven biology
Year(s) Of Engagement Activity 2018
 
Description Organised & Hosted Microbiology Society FOCUSED MEETING 2016: MOLECULAR BIOLOGY AND PATHOGENESIS OF AVIAN VIRUSES 
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 Focused Meeting on Molecular Biology and Pathogenesis of Avian Viruses took place at Charles Darwin House, London, UK.

Avian viruses have contributed immensely to our understanding of not only virology but important aspects of biology including cancer, immunology and cell biology.

In recent years, the role of birds as sources of important zoonotic viruses (avian influenza, West Nile, Japanese encephalitis, the equine encephalitis viruses) has become apparent. Poultry (reaching a global annual population of around 55 billion chickens) are also increasingly important as a universally acceptable source of protein for a growing world population. With a plethora of viruses, with frequent occurrence of emergence of novel pathogens and continuing diversity, the vaccination strategies widely used by the industry are being challenged.

With significant growth of the poultry population happening in Asia and South America, where emergence and re-emergence of avian viral pathogens is often observed, this timely meeting focusing on avian viruses will bring together the international scientific community to assess the extent of the problem and help find solutions. Those working on key, often novel, aspects of the molecular biology and pathogenesis of a range of important avian viruses will join others studying host-virus interactions using genetics, genomics, transcriptomics and proteomics, especially in the study of the innate (particularly interferon) responses.

Topics will include:

Molecular biology and genetics of avian virus replication
Tropism and host range restriction
Pathogenesis of avian viruses
Host antiviral responses and virus immunomodulation
New and improved approaches to the control of avian viruses
Organisers: Dr Mike Skinner (Imperial College London, UK) and Professor Venugopal Nair (The Pirbright Institute, UK).

Approved by the Royal Society of Biology for purposes of CPD, this event may be counted as 42 CPD credits.
Year(s) Of Engagement Activity 2016
URL https://microbiologysociety.org/event/society-events-and-meetings/focused-meeting-2016-molecular-bio...
 
Description Organised the 3rd UK-China CERAD meeting in Guildford, UK in July 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 The 3rd UK-China CERAD meeting helped to bring together professional from both countries to identify challenges and exploit the opportunities for improved control of poultry diseases and increasing food security.
Year(s) Of Engagement Activity 2017
URL http://www.uk-china-cerad.org/
 
Description Organising and giving Keynote talk at the GARAD meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Global Alliance of Poultry industry professional and academia to discuss about the advances in control strategies of diseases
Year(s) Of Engagement Activity 2018
URL http://Garad.org
 
Description Planned, introduction and chairing SGM debate on Influenza "Gain-of-Function" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Wendy Barclay planned & introduced debate on Influenza "Gain-of-Function" controversy at Society for General Microbiology Annual Conference, Birmingham 30 Mar-1 Apr 2015. Mike Skinner chaired the debate which was attended by >300 scientists (including many PhD students) and regulators.
Year(s) Of Engagement Activity 2015
URL http://www.microbiologysociety.org/all-microsite-sections/microbiology-today/index.cfm/article/8D4A5...
 
Description Poultry Health Course (Pirbright) 
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 The course is organised for participants from Brazil to understand the current advances in poultry diseases.
Year(s) Of Engagement Activity 2017
URL http://www.poultryhealthcourse.com/
 
Description Poultry Health course 
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 Poultry Health Course is run as a residential and online course to transfer recent advances in avian disease research from the laboratory to the field.
Year(s) Of Engagement Activity Pre-2006
URL http://www.poultryhealthcourse.com/
 
Description Second Symposium of the UK-China Centre of Excellence for Research on Avian Diseases held in March 2016 in Binzhou, Shandong Province, China 
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 second international meeting of the UK-China CERAD was attended by a number of delegates from both UK and China and reviewed the progress. Plans were drawn of further activities and plans for securing additional grants.
Year(s) Of Engagement Activity 2016
 
Description TedX Glasgow 
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 ~900 views. https://www.youtube.com/watch?v=DUbqrh5otWs
Year(s) Of Engagement Activity 2017