Analysis of innate immune responses in vivo and the control of effective immune responses to infection

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

Abstract

While studies of innate immune responses to stimulatory agonists and pathogens in in vitro systems will provide a powerful framework of knowledge on the nature and regulation of innate responses in the target animal species, responses to infection in vivo will also be influenced by the microenvironment in which the pathogen-host cell interaction occurs. Innate immune responses contribute to control of infection not only by triggering non-specific defense mechanisms but also by regulating the adaptive immune response. The latter operates largely through antigen-presenting cells (APC), and their capacity to influence differentiation of T lymphocytes. We aim to extend the work in earlier themes, by examining in vivo responses of APC to infection and their capacity to induce specific T cell responses. The work will focus particularly on intracellular pathogens and will include studies to characterise relevant subsets of APC and T lymphocytes in the target species.

Publications

10 25 50

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Rothwell L (2012) Chicken interleukin-21 is costimulatory for T cells and blocks maturation of dendritic cells. in Developmental and comparative immunology

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Wright DM (2013) Detectability of bovine TB using the tuberculin skin test does not vary significantly according to pathogen genotype within Northern Ireland. in Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases

 
Description Highlights of ISP theme 'Analysis of innate immune responses in vivo and the control of effective immune responses to infection'
This theme aims to interrogate innate responses in vivo and identify innate response pathways that influence the ability of the adaptive immune response to control or eliminate infection:

1. Afferent Lymphatic cannulation
We have re-established the afferent lymphatic cannulation technique at RI with significant ISP funding. This was a major effort with significant input from B Charleston and the team at Dryden farm. We now have the technique up and running with surgeries being performed by C Bell with significant input from I McGuinnes (ISP funded plus one). We have refined the technique in line with the 3Rs such that our success rate (where lymph flows for >48h from an identified afferent lymphatic vessel) has improved from ~50% to over 70%. This means that we can use fewer animals to achieve our objectives. In addition, we have introduced refinements to animal husbandry and maintenance which reduce the overall severity of the technique and improve the longevity of the lymph collection period. A biobank of cells has been established which will underpin future ISP objectives.
We have examined the potential for DCs in afferent lymph to cross-present antigens from T. parva to CD8+ T cells (I Morrison and C Bell). We have shown that NK cells recirculate through the lymph (Hamilton et al, 2017) and provided preliminary data to show that the frequency and phenotype of NK cells in the lymph is significantly altered following BCG vaccination (Hamilton PhD thesis). We also demonstrated that BCG vaccination induces significant alterations in the frequency of DCs present within the lymph (unpublished). This extends the previously published data on BCG uptake by afferent lymph DCs (Hope et al, 2012). An output from this aspect of the ISP is a BBSRC funded project in the Vaccinology Highlight call (BBSRC BB/P003958/1 awarded to J Hope, I Morrison, T Freeman and C Bell; 80% FEC value £697k). This project started in February 2017. This allows the functional and phenotypic properties of cells exposed to BCG to be investigated including analysis of genes associated with specific stimulation of T cell subsets. We aim to further investigate DC interactions with M. bovis and the subsequent reciprocal interactions with gamma delta T cells (E Anderson PCDS studentship) to define mechanisms whereby priming or licencing of DCs influences the nature of the CD4+ T cell response. This will enable us to pinpoint targets for improved vaccine design or adjuvants.

2. Novel adjuvant analysis
Alongside the afferent DCs we have examined the response of monocyte derived DCs to a novel adjuvant (cobalt oxide) in collaboration with S Howie (QMRI). This has enabled us to extend and translate studies performed in mice to demonstrate that cobalt nanoparticles can act as adjuvants as well as Ag delivery systems in the absence of inflammation or adverse effects (e.g. cytotoxicity) in vitro and in vivo. The use of this novel adjuvant to deliver a TB vaccine candidate Ag (Ag85A) was shown in a small cohort of calves. These data are currently being extended with MRC Confidence in Concept Funding in collaboration with an industrial partner (Benchmark Ltd) interested in developing adjuvants for both large animals and fish. We will use this novel adjuvant alongside the TB vaccine candidate Ag in a new project funded by BBSRC (Single-Administration Vaccine Enhancement, BB/R008272/1 & BB/R007616/1). In this collaborative project with Heriot Watt university we will produce 3D printed capsules which can be engineered to deliver a booster vaccine at defined time points enabling one-time vaccination of calves for long term protective immunity.

3. Vaccine development for Mycobacterium avium paratuberculosis
Under ISP and grant (BB/H010718/1) funding, we demonstrated that an adenovirus-MVA prime boost vaccine could significantly protect calves from infection with Mycobacterium avium paratuberculosis. A number of immunological correlates of protection, measured as a highly significant reduction in bacterial load in the gut, were defined and we will seek further funding to examine these in more detail. An ongoing PhD studentship in the BBSRC EASTBIO scheme is examining the response of bovine APCs to infection with strains of MAP that differ in virulence. This project aims to compare a field strain isolated from a clinical case of Johne's disease with the lab adapted sequence strain of MAP. Significant differences in intracellular killing, cytokine profiles and uptake pathways have been identified.

4. Identification of a novel subset of T lymphocytes in cattle
We have identified a novel subset of T lymphocytes in cattle, based on expression of the NK cell marker NKp46. These cells are present as a small discrete population from birth onwards. Unlike other unconventional T cell subsets, they express a diverse T cell repertoire. They are functionally distinct from conventional T cells and NK cells, sharing some properties of both, and hence have the potential to participate in both innate and adaptive immune responses.
Work has focused on understanding the bovine response to non-conventional antigens. Currently the work indicates the presence of a population of T-cells that respond to lipoproteins. This response appears to more specific to tuberculosis-complex mycobacteria that the conventional peptide antigens and may therefore offer an improved diagnostic target. Continuing work will focus on lipid-specific T-cells with the intention of being able to incorporate these novel antigens into future vaccine developments.

5. Antigen processing pathways in parasitized cells
Endogenous processing of antigen for recognition by CD4 T cell: The conventional route of antigen processing for CD4 T cell recognition involves processing within the endosomal compartment following uptake from the extracellular environment. Cells infected with Theileria parasites express high levels of MHC (both class I and class II), as well as co-stimulatory molecules, on their cell surface and are therefore able to present antigen directly to T cells. We have shown that processing of antigens recognised by CD4 T cells on infected cells is proteasome-dependent and largely independent of endosomal cathepsin activities. These findings indicate that processing occurs via an endogenous pathway and implies that generation of similar responses by vaccination may require a vaccine formulation that results in endogenous processing.

6. Functional differentiation of T cell responses
There is well established evidence that CD8 T cells play a central role in immunity to the bovine protozoan parasite Theileria parva, and a number of parasite antigens recognised by CD8 T cells from immune cattle have been identified. However, attempts to vaccinate cattle using viral vectors have resulted in only partial immunity in some animals. This has provided a model system to compare the T cell responses induced by a non-protective (prime-boost viral vectors) and protective (live parasite) vaccines, to identify those features that are critical for immunity. We have shown that the magnitude of the responses induced by both vaccines and the kinetics of recall if the responses following parasite challenge are similar for both immunisation methods. However, in contrast to responses induced by live parasites, the CD8 T cells generated by immunisation with viral vectors exhibit poor cytotoxic activity against the parasite-infected cells, indicating that there is defect in functional differentiation of the specific CD8 T cells. Our findings indicate that this defect is attributable to other cell types, most likely CD4 T cells. We are now collaborating with the Earlham Institute in relation to single cell sequencing of T-cells from protective and non-protective responses.

7. Parasite genetic and antigenic diversity
Immunity induced by one strain of Theileria parva does not provide complete protection against challenge with some heterologous strains. This is associated with polymorphism in the antigens recognised by immune CD8 T cells. High throughput sequencing of PCR amplicons of genes encoding CD8 antigens has been used to examine genotypic diversity of parasite populations in infected cattle and buffalo (the wildlife reservoir) in the field. These studies have revealed a number of key findings:
- All of the parasite genes exhibit allelic diversity at the nucleotide level, but a subset of them are highly conserved at the amino acid level. Parallel studies indicate that following infection these conserved proteins induce much weaker CD8 T cell responses compared to those induced by the more variable genes.
- Multiple allelic variants of each parasite gene are detected in single samples from each animal, indicating that the infections arise from multiple infection events.
- Parasites in infected buffalo exhibit much greater diversity than those in cattle. Overall, the results indicate that the cattle-maintained parasites represent a subset of those found in buffalo, which have adapted to efficient transmission between cattle.
- Comparison of gene sequences of parasites from buffalo in Kenya and South Africa demonstrate that most of the sequence diversity is observed in both populations, indicating that diversification has occurred predominantly before geographical separation.

8. A high throughput sequencing method to define MHCI genes in cattle, pigs goats sheep and horses
Using PCR primers that amplify all expressed alleles and by incorporating individual animal identifier tags, it is now possible to obtain definitive typing of all expressed class I genes in multiple livestock species, examining up to 200 individuals in a single sequencing run. The majority of work has so far been carried out in cattle and similar approaches are being developed for MHCII genes: DRB3, DQA and DQB in cattle. Application of this method will enable complete characterisation of MHC genotypes in the Holstein breed and comparison of these genotypes with other breeds of cattle.
We have started characterising the global diversity of bovine MHC collecting samples from Zambia, Uganda, Cameroon, Kenya, Pakistan, Brazil and Italy. Additional sampling is planned for China, Turkey, Poland, Ghana and south America. The data from the work already conducted has shown evidence of evolutionary divergence of MHC molecules between the different cattle lineages (bos taurus european, bos taurus africanus and bos indicus) and we plan to integrate the data generated with other activities (e.g. peptide-MHC elution studie and epitope prediction algorithms) to rapidly fill a current gap in knowledge with direct relevance to vaccine development for cattle - how MHC influences epitope selection.

9. Peptide elution studies to define immunogenic peptides and aid vaccine development
We have collaborated with Oxford University to apply peptide-MHCI elution studies from Theileria infected cells. The data from these studies have enabled us to produce refined peptide-binding motifs for the relevant MHCI alleles (Led by Porf. M Nielsen, University of Copenhagen), and this has identified Theileria antigens that are preferentially entering the MHC pathways (which may lead on to the identification of novel antigens to be incorporated into future vaccines) and has provided information about how the structure of different bovine MHCI haplotypes may influence the immunopeptidome (i.e. the peptides presented by MHC molecules) that will influence future antigen identification strategies.
Furthemore, we have preliminary data showing that epitopes that are immunodominant in MHC homozygous animals are not relevant to animal that have the same MHC but are heterozygous. We now have data confirming that this can directly impact on the performance of candidate vaccines. By developing a fully MHC defined herd at Langhill we will have critical animal resources to further explore this area.
We have generated bovine class I MHC tetramers that allow identification and purification of epitope-specific CD8 T cells (In collaboration with workers in Denmark and Bristol). This allows generation of precise data on the kinetics of antigenic-specific CD8 T cell responses and isolation of the specific T cells for functional analyses.

10. Annotation of the bovine T cell receptor beta and alpha/delta gene loci
This has provided essential reference data on the variable gene repertoires, which for the first time allows detailed analyses of the clonal composition of bovine antigen-specific T cell populations during infection and/or immunisation. We have now generated NGS based technologies to permit high resolution analysis of TCR repertoires. We have data for cattle TRB and TRD repertoires and have secured additional funding to extend these technologies to sheep, pigs, goat and water.

11. Antibody generation
We have generated antibodies against bovine CD107a (degranulation marker that can be used to identify responding NK cells and antigen-specific T-cells). This antibody has been used to study the imunobiology of trypanosome infections in cattle and also to help study the kinetics and magnitude of Theileria-specific responses ex vivo. We have also generate antibodies against bovine CD137 and CD152, but further validation of these is required.
Exploitation Route The work continues to develop methods and generate reagents that are of value to scientists and the commercial sector interested in examining innate and adaptive responses to livestock infections and vaccines. The work is now broadening its scope to livestock breeds and their infectious diseases of importance in LMICs. Vaccine and adjuvant development will hopefully be taken forward with commercial partners.
Sectors Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology

 
Description Most of the research from this theme is still developmental, but with significant progress in reagents and methods to dissect livestock host innate responses. The main areas of impact have been training of personnel, particular in rare skills including surgical techniques and basic knowledge underpinning development of novel diagnostics and vaccines. In general, BBSRC strategic investment at Roslin via this and other Institute Strategic Programmes has sustained expertise and facilities that have attracted substantial inward investment at Easter Bush. This has recently included £15M Gates Foundation funding to establish the Centre for Tropical Livestock Genetics & Health to implement genetic gain and treatments in support of farmers in low- and middle-income farmers, including to control endemic and zoonotic diseases. It has also driven dozens of productive collaborations with industry via contracts and leveraging schemes, leading to £10M private equity investment to form Roslin Technologies to commercialise our research and construction of a new £32M Innovation Centre adjacent to the Institute to engage and grow businesses. Moreover, the expertise supported by this funding has attracted major investment in Agri-Tech Centres at Easter Bush funded by InnovateUK (Centre for Innovation Excellence in Livestock & Agri-EPI). These Centres will increase national capacity for infectious challenge in farmed animals, gene editing and collection of novel phenotypes and be linked to stakeholders throughout the food supply chain
First Year Of Impact 2013
Sector Agriculture, Food and Drink
Impact Types Societal,Economic

 
Description BBSRC Industrial Partnering Award
Amount £1,500,000 (GBP)
Funding ID BB/P022049/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2017 
End 09/2020
 
Description BBSRC LINK
Amount £336,000 (GBP)
Funding ID BB/K00638X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2013 
End 09/2016
 
Description BBSRC Responsive Mode
Amount £644,177 (GBP)
Funding ID BB/R008272/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 03/2021
 
Description BBSRC Strategic LoLa scheme
Amount £5,700,000 (GBP)
Funding ID BB/N001591/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2017 
End 03/2021
 
Description BBSRC Vaccinology Highlight
Amount £696,488 (GBP)
Funding ID BB/P003958/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 02/2017 
End 01/2020
 
Description BBSRC-DBT joint call for proposals Farmed Animal Disease and Health (FADH)
Amount £428,822 (GBP)
Funding ID BB/L004739/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2014 
End 09/2017
 
Description BMGF grant
Amount £2,050,805 (GBP)
Funding ID BMGF OPP1108042 and OPP1126862 
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 05/2014 
End 04/2017
 
Description CASE studentship
Amount £94,126 (GBP)
Funding ID 1509513 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2014 
End 09/2018
 
Description Development and testing of Operational Models of Bovine Tuberculosis in British Cattle and Badgers
Amount £22,454 (GBP)
Organisation Department For Environment, Food And Rural Affairs (DEFRA) 
Sector Public
Country United Kingdom
Start 05/2015 
End 08/2016
 
Description European Commission H2020-INFRAIA-2016-1
Amount € 10,000,000 (EUR)
Funding ID EU project 731014 
Organisation European Commission H2020 
Sector Public
Country Belgium
Start 04/2017 
End 03/2022
 
Description MRC Confidence in Concept Scheme
Amount £89,205 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2016 
End 09/2017
 
Description Study of the immunobiology of M cells (Sehgal)
Amount £75,000 (GBP)
Funding ID EASTBIO DTP 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2012 
End 08/2016
 
Description Welcome Trust Pathfinder
Amount £129,709 (GBP)
Funding ID 204521/Z/16/Z 
Organisation Wellcome Trust 
Department Wellcome Trust Bloomsbury Centre
Sector Academic/University
Country United Kingdom
Start 01/2017 
End 06/2018
 
Description open call
Amount £379,303 (GBP)
Funding ID BB/L004003/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2014 
End 04/2017
 
Title ELispot for PCV2 
Description The assay is able to detect a cellular immune response to PCV2. 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? No  
Impact Improvement of vaccine efficacy assessment. 
 
Title In vitro culture of bovine intestinal enteroids 
Description We have developed the methodology for generating and culturing bovine intestinal enteroids - stem cell-derived 3-dimensional structures, including a lumen and crypts, and with all cell types represented. Importantly these are able to be continuously passaged, and can be cryopreserved. Therefore, they are (i) a more physiologically relevant in vitro model for the bovine intestine, (ii) represent a viable route to replacing animal use in the study of the bovine intestine - for example, in host-pathogen studies of important bovine enteric pathogens (potentially including drug screening). 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2018 
Provided To Others? Yes  
Impact While it is too early to assess impact of our research tool, we have already had multiple enquiries for collaboration and requests for advice on use of the technique, both within Roslin Institute and from external institutions. We predict that this will lead to a reduction in animal use as the use of enteroids becomes more wiodespread. 
 
Description Bovine gamma delta T cells 
Organisation University of Massachusetts
Country United States 
Sector Academic/University 
PI Contribution This builds upon a long term partnership between J Hope and C Baldwin group who have common interests in bovine gamma delta T cells. This resulted in a grant award to Baldwin, Telfer (both U Mass), Connelley and Hope (both Roslin). J Hope contributed scientific knowledge and background to the development of a grant proposal to USDA-NIFA to assess expression of T cell receptors. Dr Connelley will provide scientific input and be directly involved in sequencing the T cell receptor genes.
Collaborator Contribution The Baldwin and Telfer groups at UMass have worked on bovine gamma delta T cells for a significant period of time and provide expertise on the biology of gamma delta T cells in leptospira and Mycobacterial infections and extensive knowledge of WC1 receptor family expressed by these cells.
Impact USDA-NIFA AFRI animal health award (#2016-09379; Role of the T cell receptor in interacting with WC1 for bovine gamma delta T cell activation).
Start Year 2012
 
Description Bovine mycobacteria in vivo studies 
Organisation Agri-Food and Biosciences Institute
Country United Kingdom 
Sector Public 
PI Contribution We have studied immune cell populations in cattle infected with M bovis and M. avium paratuberculosis to define correlates of protective immunity.
Collaborator Contribution Provided blood and tissue samples from infected cattle as part of their ongoing studies. Provided laboratory space and assistance for a PhD student visiting to collect samples.
Impact This collaboration contributed to PhD theses from C Hamilton and H Mathie.
Start Year 2012
 
Description Cameroon Infectious disease epidemiology links 
Organisation Cameroonian Academy of Sciences
Country Cameroon 
Sector Academic/University 
PI Contribution expertise in infectious diseases epidemiology and study design. We currently have 2 BBSRC GCRF Impact Accelerator Awards active in Cameroon as part of ongoing links and collaborations.
Collaborator Contribution expertise in infectious disease logistics local setting transport accommodation.
Impact Grant on HPAI in North Cameroon - no funded Grant on FMD in Adamawa Region Cameroon - not funded 1 month collection of FMD samples - paper in preparation use of samples from TB project to screen for RVF - 2 papers in preparation
Start Year 2011
 
Description Collaboration with AB Vista 
Organisation AB Vista
Country United Kingdom 
Sector Private 
PI Contribution We are researching the activity of ovodefensins, naturally-occurring egg peptides with antimicrobial properties. With BBSRC LINK funding we are exploring the activity of diverse ovodefensins from multiple avian species, dissecting their structure and mode of action, and exploring their capacity to act as growth promoters and novel therapeutics.
Collaborator Contribution AB Vista have made a substantial cash contribution to the LINK project (c. £460k) and also provide access to natural populations of broilers for feed trials using diets supplemented (or not) with Trichoderma-expressed ovodefensins. They also support analysis of the impact of such diets on intestinal microbiota and metabolites.
Impact Commercially sensitive and to be disclosed following scrutiny for Intellectual Property.
Start Year 2012
 
Description Immune correlates and immune resources for ruminants 
Organisation Moredun Research Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Myeloid cell biology of ruminants Transcriptome analysis of ruminant myeloid cells
Collaborator Contribution Development of resources for sheep and cattle immunity Host-pathogen interactions involving ruminant innate cells Ruminant innate cell interactions with acquired immune cell populations Vaccines
Impact Outputs See: BB/I020519/1; BB/I019863/1; BB/J500513/1 Publications: Corripio-Miyar Y, Hope J, McInnes CJ, Wattegedera SR, Jensen K, Pang Y, Entrican G.. Glass EJ. (2015). Phenotypic and functional analysis of monocyte populations in cattle peripheral blood identifies a subset with high endocytic and allogeneic T-cell stimulatory capacity. Veterinary research, 46:112. Doull L, Wattegedera S, Longbottom D, Mwangi D, Nath M, Glass E, Entrican G. (2015). Late production of CXCL8 in ruminant oro-nasal turbinate cells in response to Chlamydia abortus infection. Veterinary Immunology and Immunopathology, 168 (1-2), pp. 97-102.
 
Description Proxima 
Organisation Proxima Concepts Limited
PI Contribution Generated preliminary data to apply for funding which was successful.
Collaborator Contribution Supplied material to test in in vivo experiments to apply for funding.
Impact Obtained multiple joined small and large research grants
Start Year 2018
 
Description Study of M cell immunobiology and their role in mucosally-acquired infections 
Organisation Tohoku University
Department Graduate School of Medicine
Country Japan 
Sector Academic/University 
PI Contribution Dr. Atsushi Kobayashi worked within my research group for 2 years here at The Roslin Institute.
Collaborator Contribution Dr. Dr. Atsushi Kobayashi brought his expertise here for two years and worked as a visiting scientist in my research group.
Impact Several publications: DNA RESEARCH 19, 407-422, (2012); doi:10.1093/dnares/dss022 Mucosal Immunology 5, 216-225; doi: 10.1038/mi.2011.68 Mucosal Immunology 6, 1027-1037; doi:10.1038/mi.2012.141 Mucosal Immunology 6, 666-677; doi:10.1038/mi.2013.30
Start Year 2011
 
Description Study of M cell immunobiology and their role in mucosally-acquired infections (Emory) 
Organisation Emory University
Country United States 
Sector Academic/University 
PI Contribution We provided the ageing and prion disease pathogenesis mouse models
Collaborator Contribution Prof. Ifor Williams provided expertise in M cell immunobiology and mucosal immunology. Prof. Williams also provided unique M-cell-deficient mice (Vil1-Cre Rank-flox mice) as well as reagents to synthesise murine recombinant gst-RANKL. These were invaluable for the study of M cells in mice in vivo.
Impact Several publications: DNA RESEARCH 19, 407-422, (2012); doi:10.1093/dnares/dss022 Mucosal Immunology 5, 216-225; doi: 10.1038/mi.2011.68 Mucosal Immunology 6, 1027-1037; doi:10.1038/mi.2012.141 Mucosal Immunology 6, 666-677; doi:10.1038/mi.2013.30 Nat Nanotechnol. 2015 Apr;10(4):361-9; DOI: 10.1038/NNANO.2015.19 PLoS Pathog 12(12): e1006075; doi:10.1371/journal.ppat.1006075 Prof. WIlliams is also a named collaborator on the following BBSRC grants: BB/J014672/1 BB/M024288/1 BB/K021257/1
Start Year 2009
 
Description Study of M cell immunobiology and their role in mucosally-acquired infections (RIKEN) 
Organisation RIKEN
Department RIKEN Center for Integrative Medical Sciences (IMS)
Country Japan 
Sector Hospitals 
PI Contribution We provided the ageing and prion disease pathogenesis mouse models.
Collaborator Contribution Prof. Hiroshi Ohno and his colleagues provided expertise in M cell immunobiology.
Impact Several publications: DNA RESEARCH 19, 407-422, (2012); doi:10.1093/dnares/dss022 Mucosal Immunology 5, 216-225; doi: 10.1038/mi.2011.68 Mucosal Immunology 6, 1027-1037; doi:10.1038/mi.2012.141 Mucosal Immunology 6, 666-677; doi:10.1038/mi.2013.30 Prof. Ohno is also a named collaborator on the following BBSRC grants: BB/J014672/1 BB/M024288/1 and BBSRC Japan Partnering Award
Start Year 2007
 
Description Study of role of IL25 in lymphoid tissue development 
Organisation University of Pennsylvania
Department Perelman School of Medicine
Country United States 
Sector Academic/University 
PI Contribution We provided mouse models in which the status of gut-associated lymphoid tissues could be manipulated.
Collaborator Contribution Prof. David Artis provided IL25-deficient mice as well as substantial expertise in mucosal immunology and the influence of the microbiota on gut-associated lymphoid tissue development.
Impact Mucosal Immunol. 2015 May;8(3):582-95; doi:10.1038/mi.2014.90
Start Year 2011
 
Description Study of role of sialoadhesin in prion disease pathogenesis 
Organisation University of Dundee
Department Division of Population Health Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We provided the mouse prion disease pathogenesis models
Collaborator Contribution Prof. Paul R. Crocker provided expertise in glycoimmunology as well as CD169-deficient mice
Impact Immunology, 143, 120-129 (2014); doi:10.1111/imm.12294
Start Year 2012
 
Description Study role of CXCR5 expression in ILC3 cells 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution We provided the unique CXCR5-floxed mice created in this project to Dr. Matthew Hepworth at the University of Manchester.
Collaborator Contribution The CXCR5-floxed mice were crossed to ID2 ER2 Cre - ROSA-RFP mice to enable the study of effects of CXCR5-deficiency in ILC3 cells.
Impact Manuscript published in the Journal of Experimental Medicine in February 2019. PMID:30814299 "Antigen presenting ILC3 regulate T cell-dependent IgA responses to colonic mucosal bacteria" by Felipe Melo-Gonzalez, Hana Kammoun, Elza Evren, Emma Dutton, Markella Papadopoulou, Barry Bradford, Ceylan Tanes, Fahmina Fardus-Reid, Jonathan Swann, Kyle Bittinger, Neil Mabbott, Bruce Vallance, Tim Willinger, David Withers, and Matthew Hepworth
Start Year 2017
 
Description Brain infection study reveals how disease spreads from gut 
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 Press release describing our study published in the Journal of Virology: http://jvi.asm.org/content/89/18/9532.long
Year(s) Of Engagement Activity 2015
URL http://www.ed.ac.uk/news/2015/prions-040815
 
Description British society for Immunology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Poster presentation at the British Society for Immunology, Dec 2017. Poster entitled: Precision cut lung slices: A platform for examining host-pathogen interactions in an avian model. Authors on the posters: Bryson K, Esposito M., Lamont S., Stevens M., McLaughlan G. and Vervelde L.
Year(s) Of Engagement Activity 2017
 
Description Career event at Earlston High 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Participated in school careers event at Earlston Highschool for pupils of S1.
Participated as STEM ambassador, multiple talks on career as scientist including activity People like me set up by STEM.
Year(s) Of Engagement Activity 2016
 
Description Gut cells are gatekeepers of infectious brain diseases, study finds 
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 Press release via the media describing our recent research published in PLoS Pathogens
Year(s) Of Engagement Activity 2016
URL http://www.bbsrc.ac.uk/news/health/2016/161214-pr-gut-cells-gatekeepers-of-infectious-brain-diseases...
 
Description Immunology conference (Germany) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Oral presentation at the avian immunology research group meeting in Germany, Sept 2016.
Audience included industry members post graduate students, junior and senior scientists.
UK was voted to be the organisers of the next meeting in 2018 in Oxford and I will be part of the organising team. This will lead to great publicity for the funded avian immunology research funded by the RCUK.
Year(s) Of Engagement Activity 2016
URL http://www.airg2016.vetmed.uni-muenchen.de/airg_2018/index.html
 
Description Invited speaker at the fifth Edinburgh Infectious Diseases Annual Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Talk at the fifth Edinburgh Infectious Diseases Annual Symposium, sparked vivid discussions and awareness of the use of livestock animals for fundamental research.
Year(s) Of Engagement Activity 2016
URL http://www.eid.ed.ac.uk/symposium2016
 
Description Keeping bugs at Bay: a Public Engagement Activity at the Roslin Institute 2014 
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 This activity aims to teach people how the immune system fights bugs.
Year(s) Of Engagement Activity 2014
 
Description Keeping bugs at Bay: a Public Engagement Activity at the Royal Highland Show 2015 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact This activity aims to teach people how the immune system fights bugs.
Year(s) Of Engagement Activity 2015
 
Description Public lecture entitled Confronting the Microbial Menace in Our Food'. Professor Mark Stevens 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact The inaugural lecture of Professor Mark Stevens was held on 30 October 2017 on his BBSRC-funded research to identify bacterial and host factors influencing the ability of Salmonella, Campylobacter and E. coli to colonise farm animals and cause disease. It was attended by children from local schools, members of the public, students at The Roslin Institute and wider University of Edinburgh and posted online.
Year(s) Of Engagement Activity 2017,2018
URL https://media.ed.ac.uk/media/Inaugural+lectureA+Confronting+the+microbial+menace+in+our+food/1_x5k5e...
 
Description Swine Practitioner workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Practitioner meeting in France to inform them on new insights on vaccination protocols.
Year(s) Of Engagement Activity 2017