Pete Kaiser

The University of Edinburgh, Edinburgh, Scotland, United Kingdom

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Publications (144)449.66 Total impact

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    ABSTRACT: Avian pathogenic Escherichia coli (APEC) infections are a serious impediment to sustainable poultry production worldwide. Licensed vaccines are available, but the immunological basis of protection is ill-defined and a need exists to extend cross-serotype efficacy. Here, we analysed innate and adaptive responses induced by commercial vaccines in turkeys. Both a live-attenuated APEC O78 ΔaroA vaccine (Poulvac® E. coli) and a formalin-inactivated APEC O78 bacterin conferred significant protection against homologous intra-airsac challenge in a model of acute colibacillosis. Analysis of expression levels of signature cytokine mRNAs indicated that both vaccines induced a predominantly Th2 response in the spleen. Both vaccines resulted in increased levels of serum O78-specific IgY detected by ELISA and significant splenocyte recall responses to soluble APEC antigens at post-vaccination and post-challenge periods. Supplementing a non-adjuvanted inactivated vaccine with Th2-biasing (Titermax® Gold or aluminium hydroxide) or Th1-biasing (CASAC or CpG motifs) adjuvants, suggested that Th2-biasing adjuvants may give more protection. However, all adjuvants tested augmented humoral responses and protection relative to controls. Our data highlight the importance of both cell-mediated and antibody responses in APEC vaccine-mediated protection toward the control of a key avian endemic disease.
    Veterinary Research 12/2015; 46(1):5. DOI:10.1186/s13567-014-0132-5 · 3.38 Impact Factor
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    ABSTRACT: Avian pathogenic Escherichia coli (APEC) exert substantial economic costs on poultry producers worldwide. Vaccination is an attractive method of control, but the immunological basis of protection is poorly understood. Here, we examine the effect of intramuscular injection of cyclophosphamide or saline on homologous protection induced by licensed inactivated or live-attenuated APEC O78 vaccines in chickens. In saline-treated birds, both vaccines induced significant APEC-specific IgY and protection against homologous challenge, as evidenced by enumeration of tissue-associated bacteria and analysis of pathology. In cyclophosphamide-treated birds, B cells were severely depleted whereas percentages of circulating CD4- and CD8-positive T cells were normal as detected by flow cytometry. Further, such birds did not produce APEC-specific IgY and were as susceptible to challenge as age-matched unvaccinated controls. The data indicate that homologous protection conferred by licensed APEC vaccines strictly requires a cyclophosphamide-sensitive cell population that includes B cells. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 06/2015; DOI:10.1016/j.vaccine.2015.06.034 · 3.49 Impact Factor
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    ABSTRACT: A new member of the chicken TNF superfamily has recently been identified, namely receptor activator of NF-κB ligand (RANKL), as have its signalling receptor, RANK, and its decoy receptor, osteoprotegerin (OPG). In mammals, RANKL and RANK are transmembrane proteins expressed on the surface of Th1 cells and dendritic cells (DC) respectively, whereas OPG is expressed as a soluble protein from osteoblasts and DC. Recombinant soluble chicken RANKL (chRANKL) forms homotrimers whereas chicken OPG (chOPG) forms homodimers, characteristic of these molecules in mammals. ChRANKL, chRANK and chOPG are expressed at the mRNA level in most tissues and organs. ChRANKL is transcriptionally regulated by Ca(2+) mobilisation and enhances the mRNA expression levels of pro-inflammatory cytokines in bone marrow-derived DC (BMDC); this is inhibited by both chOPG-Fc and soluble chRANK-Fc. However, chRANKL does not enhance the expression of cell surface markers in either BMDC or BM-derived macrophages (BMM). Furthermore, chRANKL enhances the survival of APC similar to its mammalian orthologue. Copyright © 2015. Published by Elsevier Ltd.
    Developmental and comparative immunology 03/2015; 51(1). DOI:10.1016/j.dci.2015.03.006 · 3.71 Impact Factor
  • Journal of Animal Science 01/2015; DOI:10.2527/jas.2014-8597 · 1.92 Impact Factor
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    ABSTRACT: Chicken whole genome gene expression arrays were used to analyse the host response to infection by Infectious Bursal Disease Virus (IBDV). Spleen and bursal tissue were examined from control and infected birds at 2, 3 and 4 days post-infection from two lines that differ in their resistance to IBDV infection. The host response was evaluated over this period and differences between susceptible and resistant chicken lines were examined. Anti-viral genes, including IFNA, IFNG, MX1, IFITM1, IFITM3 and IFITM5 were up-regulated in response to infection. Evaluation of this gene expression data has allowed us to predicted several genes as candidates for involvement in resistance to IBDV. Infectious bursal disease (IBD) is of economic importance to the poultry industry and thus is also important for food security. Vaccines are available but field strains of the virus are of increasing virulence. There is thus an urgent need to explore new control solutions, one of which would be to breed birds with greater resistance to IBD. A goal which is perhaps uniquely achievable with poultry, of all farm animal species, as the genetics of 85% of the 60 billion chickens produced worldwide each year is under the control of essentially two breeding companies. This is the most comprehensive study to try to identify global transcriptomic differences in the target organ of the virus between chicken lines that differ in resistance, and to predict candidate resistance genes. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Journal of Virology 12/2014; 89(5). DOI:10.1128/JVI.02828-14 · 4.65 Impact Factor
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    ABSTRACT: Chickens raised under village production systems are exposed to a wide variety of pathogens, and current or previous infections may affect their susceptibility to further infections with another parasite, and/or can alter the manifestation of each infection. It is possible that co-infections may be as important as environmental risk factors. However, in cross-sectional studies, where the timing of infection is unknown, apparent associations between infections may be observed due to parasites sharing common risk factors. This study measured antibody titres to 3 viral (Newcastle disease, Marek's disease and infectious bursal disease) and 2 bacterial (Pasteurella multocida and Salmonella) diseases, and the infection prevalence of 3 families of endo- and ecto-parasites (Ascaridida, Eimeria and lice) in 1056 village chickens from two geographically distinct populations in Ethiopia. Samples were collected during 4 cross-sectional surveys, each approximately 6 months apart. Constrained ordination, a technique for analysis of ecological community data, was used to explore this complex dataset and enabled potential relationships to be uncovered and tested despite the different measurements used for the different parasites. It was found that only a small proportion of variation in the data could be explained by the risk factors measured. Very few birds (9/1280) were found to be seropositive to Newcastle disease. Positive relationships were identified between Pasteurella and Salmonella titres; and between Marek's disease and parasitic infections, and these two groups of diseases were correlated with females and males respectively. This may suggest differences in the way that the immune systems of male and female chickens interact with these parasites. In conclusion, we find that a number of infectious pathogens and their interactions are likely to impact village chicken health and production. Control of these infections is likely to be of importance in future development planning.
    Preventive Veterinary Medicine 11/2014; 117(2). DOI:10.1016/j.prevetmed.2014.07.002 · 2.51 Impact Factor
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    ABSTRACT: In the poultry production industry, chickens with access to outdoor areas are exposed to a wide range of parasites e.g. the helminth Ascaridia galli. By real-time quantitative RT-PCR, the relative gene expression of the T helper 1 (Th1) cytokine IFN-γ, the T helper 2 (Th2) cytokine IL-13, the anti-inflammatory cytokines IL-10 and TGF-β4 and the pro-inflammatory cytokine IL-17F were determined over a period of 3 weeks in A. galli and non-A. galli-infected chickens. A characteristic Th2 response was observed in the jejunum of A. galli-infected chickens with increased expression of IL-13 and decreased expression of IFN-γ from day 14 post infection. At the putative time of larvae invasion into the intestinal mucosa (day 7), an increased expression of IFN-γ, IL-10, and TGF-β4 was observed in the spleen. At the putative onset of the innate immune response (day 10), a decreased expression of jejunal IFN-γ and IL-13 was observed. Finally, at the expected period of an adaptive immune response (days 14–21) a general decreased expression of IFN-γ and TGF-β4 in spleen and IFN-γ in jejunum was followed by a decreased expression of IFN-γ and IL-10 at day 21 in caecal tonsils.
    Veterinary Parasitology 10/2014; 206(3-4). DOI:10.1016/j.vetpar.2014.10.016 · 2.55 Impact Factor
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    Veterinary Immunology and Immunopathology 10/2014; DOI:10.1016/j.vetimm.2014.08.002 · 1.75 Impact Factor
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    ABSTRACT: Abstract Text: Salmonella Enteritidis is a threat to human health due to the consumption of contaminated meat or eggs. A genome wide association study was performed using a 60 K SNP chip to identify genomic regions associated with resistance to salmonella carrier-state. We genotyped 209 chicks issued from an F8 advanced intercross line between two experimental inbred lines and experimentally infected with S. Enteritidis. Their carrier-state was assessed by measuring the fecal count of S. Enteritidis 4 weeks after infection. After quality controls, 22,557 markers could be used for a genome wide association analysis performed with the plink software. Half of the markers associated with the highest probabilities were located in genomic regions previously identified for their association with resistance to S. Enteritidis carrier-state or resistance to S. Typhimurium in chicken. This study therefore confirms and refines the location of several regions of interest. Keywords: Chicken; Salmonella Enteritidis; GWAS
    10th World Congress on Genetics Applied to Livestock Production; 08/2014
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    ABSTRACT: Serological data for Salmonella and Infec-tious Bursal Disease Virus (IBDV) were recorded for 760 indigenous Ethiopian village chickens raised in two distinct geographical regions, Horro and Jarso. Chickens were gen-otyped with a 620K SNP array. A multidimensional scaling analysis showed that the two populations were genetically distinct. In Horro chickens, genome-wide scans revealed nine SNP with chromosome-wide significant association with Salmonella resistance and seven SNP with genome-wide significant association with IBDV resistance. In Jarso chickens, these scans revealed one SNP with genome-wide and two SNP with chromosome-wide significant associa-tion with Salmonella resistance, and one SNP with genome-wide and three SNP with chromosome-wide significant association with IBDV resistance. All significant SNP for each region for either disease were located on different chromosomes. Most of these SNP had a significant additive effect and were located close to annotated genes that are known to impact the immune response in chickens.
    10 th World Congress of Genetics Applied to Livestock Production; 08/2014
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    ABSTRACT: This study aimed to evaluate the response of Harderian gland (HG) cells after in vitro stimulation with class B synthetic oligodeoxyribonucleotides (ODN) containing CpG motifs. This knowledge is of importance for the development of mucosal vaccines for poultry, such as eye-drop or spray vaccines, to determine if class B CpG ODN can act as an vaccine adjuvant or as a prophylactic treatment mainly against respiratory disease viruses. The relative expression of Toll-like receptor 21 (TLR21), interferon (IFN)-γ, interleukin (IL)-1β and IL-10 genes were quantified at 1, 3, 6 and 18 h post-stimulation of HG cells from 5-week-old birds. In addition, it was also investigated if expression of these genes was affected by the age of the birds (differences between 5- and 12-week-old birds), concentrations of ODN or cell preparation method used. Class B CpG ODN induced upregulation of TLR21 and IFN-γ mRNA expression levels at 1 h post-stimulation depending on concentration of ODN used but only in HG cells isolated from young birds.
    Veterinary Immunology and Immunopathology 08/2014; 161(3-4). DOI:10.1016/j.vetimm.2014.04.010 · 1.75 Impact Factor
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    ABSTRACT: The observed genetic divergence likely emanated from limited gene flow, variation in demographic history and route and time of introduction. Moreover, the two populations might be descended from different ancestral origins and they have been established and developed under different management histories. Ecological variability and demographic structure of the community may have also contributed to this divergence. Horro chickens are genetically more homogenous than Jarso chickens (Figure 4). The optimal K was 2, however biologically meaningful pattern was observed at K = 4 following the marketsheds sampled. Table 2. Indicators of genetic diversity (mean (std)). Study site Horro Jarso Location W. Ethiopia E. Ethiopia Agro-ecology Sub-humid Semi-arid Topography Undulating Rugged Religion 98% Christians 99% Muslims Rainfall 1685mm 700mm Temperature 19°C 21°C Flock size 8 birds 4 birds Table 1. Description of the study sites. Figure 1. The study sites. Figure 2. The binned MAF.
    34th International Society for Animal Genetics, Xi'an, China; 07/2014
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    ABSTRACT: We have generated the first transgenic chickens in which reporter genes are expressed in a specific immune cell lineage, based upon control elements of the colony stimulating factor 1 receptor (CSF1R) locus. The Fms intronic regulatory element (FIRE) within CSF1R is shown to be highly conserved in amniotes and absolutely required for myeloid-restricted expression of fluorescent reporter genes. As in mammals, CSF1R-reporter genes were specifically expressed at high levels in cells of the macrophage lineage and at a much lower level in granulocytes. The cell lineage specificity of reporter gene expression was confirmed by demonstration of coincident expression with the endogenous CSF1R protein. In transgenic birds, expression of the reporter gene provided a defined marker for macrophage-lineage cells, identifying the earliest stages in the yolk sac, throughout embryonic development and in all adult tissues. The reporter genes permit detailed and dynamic visualisation of embryonic chicken macrophages. Chicken embryonic macrophages are not recruited to incisional wounds, but are able to recognise and phagocytose microbial antigens.
    Development 07/2014; 141(16). DOI:10.1242/dev.105593 · 6.27 Impact Factor
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    ABSTRACT: Campylobacter is the main cause of foodborne diarrhoeal illness in humans in the developed world and it has been estimated that 60-80% of cases are attributed to handling or consumption of chicken. Our previous studies have demonstrated that caecal Campylobacter levels in chickens can be significantly reduced by oral vaccination with Salmonella Typhimurium ∆aroA strains expressing the C. jejuni antigen CjaA. We evaluated avian pathogenic E. coli (APEC) ∆aroA expressing CjaA as a TetC fusion, or TetC, relative to S. Typhimurium ∆aroA expressing the same antigens. APEC have lower zoonotic potential and a commercially available APEC vaccine (PoulVac® E. coli) is used to control avian colibacillosis. In two trials, neither vaccine decreased caecal Campylobacter levels compared to mock-vaccinated controls, though antigen-specific humoral responses were detected. To screen other candidate antigens, 22 surface-localised and immunogenic Campylobacter proteins were cloned as GST fusions and their solubility was assessed. Nine were purified in sufficient quantities to be evaluated as subunit vaccines in chickens and three conferred up to 2log10 reductions in caecal Campylobacter carriage at 49-56 days post-hatching across at least two independent replicates. Current work will evaluate whether combining the three antigens above confers improved protection and investigates the nature of the protective immune responses.
    Avian Immunology Research Group Meeting 2014, Guelph, Canada; 07/2014
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    Mark S Gibson, Pete Kaiser, Mark Fife
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    ABSTRACT: The interleukin-1 gene family encodes a group of related proteins that exhibit a remarkable pleiotropy in the context of health and disease. The set of indispensable functions they control suggests that these genes should be found in all eukaryotic species. The ligands and receptors of this family have been primarily characterised in man and mouse. The genomes of most non-mammalian animal species sequenced so far possess all of the IL-1 receptor genes found in mammals. Yet, strikingly, very few of the ligands are identifiable in non-mammalian genomes. Our recent identification of two further IL-1 ligands in the chicken warranted a critical reappraisal of the evolution of this vitally important cytokine family. This review presents substantial data gathered across multiple, divergent metazoan genomes to unambiguously trace the origin of these genes. With the hypothesis that all of these genes, both ligands and receptors, were formed in a single ancient ancestor, extensive database mining revealed sufficient evidence to confirm this. It therefore suggests that the emergence of mammals is unrelated to the expansion of the IL-1 family. A thorough review of this cytokine family in the chicken, the most extensively studied amongst non-mammalian species, is also presented. Electronic supplementary material The online version of this article (doi:10.1007/s00251-014-0780-7) contains supplementary material, which is available to authorized users.
    Immunogenetics 05/2014; 66(7-8). DOI:10.1007/s00251-014-0780-7 · 2.49 Impact Factor
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    ABSTRACT: Avian pathogenic Escherichia coli (APEC) cause severe respiratory and systemic disease in poultry yet the nature and consequences of host immune responses to infection are poorly understood. Here, we describe a turkey sub-acute respiratory challenge model and cytokine, cell-mediated and humoral responses associated with protection against homologous re-challenge. Intra-airsac inoculation of turkeys with 105 colony-forming units of APEC O78:H9 strain chi7122nalR induced transient and mild clinical signs of colibacillosis followed by clearance of the bacteria from the lungs and visceral organs. Upon re-challenge with 107 chi7122nalR, primed birds were solidly protected against clinical signs and exhibited negligible bacterial loads in visceral organs, whereas age-matched control birds exhibited high lesion scores and bacterial loads in the organs. Levels of mRNA for signature cytokines suggested induction of a Th1 response in the lung, whereas a distinct anti-inflammatory cytokine profile was detected in the liver. Proliferative responses of splenocytes to either Concanavalin A or soluble chi7122nalR antigens were negligible prior to clearance of bacteria, but APEC-specific responses were significantly elevated at later time intervals and at re-challenge relative to control birds. Primary infection also induced significantly elevated chi7122nalR-specific serum IgY and bile IgA responses which were bactericidal against chi7122nalR and an isogenic Deltarfb mutant. Bactericidal activity was observed in the presence of immune, but not heat-inactivated immune serum, indicating that the antibodies can fix complement and are not directed solely at the lipopolysaccharide O-antigen. Such data inform the rational design of strategies to control a recalcitrant endemic disease of poultry.
    Veterinary Research 02/2014; 45(1):19. DOI:10.1186/1297-9716-45-19 · 3.38 Impact Factor
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    ABSTRACT: Coccidiosis, caused by species of the apicomplexan parasite Eimeria, is a major disease of chickens. Eimeria species are present world-wide, and are ubiquitous under intensive farming methods. However, prevalence of Eimeria species is not uniform across production systems. In developing countries such as Ethiopia, a high proportion of chicken production occurs on rural smallholdings (i.e. 'village chicken production') where infectious diseases constrain productivity and surveillance is low. Coccidiosis is reported to be prevalent in these areas. However, a reliance on oocyst morphology to determine the infecting species may impede accurate diagnosis. Here, we used cross-sectional and longitudinal studies to investigate the prevalence of Eimeria oocyst shedding at two rural sites in the Ethiopian highlands. Faecal samples were collected from 767 randomly selected chickens in May or October 2011. In addition, 110 chickens were sampled in both May and October. Eimeria oocysts were detected microscopically in 427 (56%, 95% confidence interval (95% CI) 52-59%) of the 767 faecal samples tested. Moderate clustering of positive birds was detected within households, perhaps suggesting common risk factors or exposure pathways. Seven species of Eimeria were detected by real time PCR in a subset of samples further analysed, with the prevalence of some species varying by region. Co-infections were common; 64% (23/36, 95% CI 46-79%) of positive samples contained more than one Eimeria spp. Despite frequent infection and co-infection overt clinical disease was not reported. Eimeria oocysts were detected significantly more frequently in October (248/384, 65%, 95% CI 60-69%), following the main rainy season, compared to May (179/383, 47%, 95% CI 42-52%, p < 0.001). Eimeria oocyst positivity in May did not significantly affect the likelihood of detecting Eimeria oocyst five months later perhaps suggesting infection with different species or immunologically distinct strains. Eimeria spp oocysts may be frequently detected in faecal samples from village chickens in Ethiopia. Co-infection with multiple Eimeria spp was common and almost half of Eimeria positive birds had at least one highly pathogenic species detected. Despite this, all sampled birds were free of overt disease. Although there was no evidence of a difference in the prevalence of oocysts in faecal samples between study regions, there was evidence of variation in the prevalence of some species, perhaps suggesting regional differences in exposure to risk factors associated with the birds, their management and/or location-specific environmental and ecological factors.
    BMC Veterinary Research 10/2013; 9(1):208. DOI:10.1186/1746-6148-9-208 · 1.74 Impact Factor
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    ABSTRACT: Macrophages contribute to innate and acquired immunity as well as many aspects of homeostasis and development. Studies of macrophage biology and function in birds have been hampered by a lack of definitive cell surface markers. As in mammals, avian macrophages proliferate and differentiate in response to CSF1 and IL34, acting through the shared receptor, CSF1R. CSF1R mRNA expression in the chicken is restricted to macrophages and their progenitors. To expedite studies of avian macrophage biology, we produced an avian CSF1R-Fc chimeric protein and generated a monoclonal antibody (designated ROS-AV170) against the chicken CSF1R using the chimeric protein as immunogen. Specific binding of ROS-AV170 to CSF1R was confirmed by FACS, ELISA and immunohistochemistry on tissue sections. CSF1 down-regulated cell surface expression of the CSF1R detected with ROS-AV170, but the antibody did not block CSF1 signalling. Expression of CSF1R was detected on the surface of bone marrow progenitors only after culture in the absence of CSF1, and was induced during macrophage differentiation. Constitutive surface expression of CSF1R distinguished monocytes from other myeloid cells, including heterophils and thrombocytes. This antibody will therefore be of considerable utility for the study of chicken macrophage biology. Abreviations: mAb, monoclonal antibody; BMDM, bone marrow-derived macrophages; CSF1R, colony stimulating factor 1 receptor; FACS, fluorescence-activated cell sorting; PBMC, peripheral blood monocytes; WB, western blot.
    Developmental and comparative immunology 09/2013; 42(2). DOI:10.1016/j.dci.2013.09.011 · 3.71 Impact Factor
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    ABSTRACT: Campylobacter is the main cause of foodborne diarrhoeal illness in humans in the developed world and it has been estimated that 60–80% of cases are attributed to handling or consumption of chicken. Our previous studies have demonstrated that caecal Campylobacter levels in chickens can be significantly reduced by oral vaccination with Salmonella Typhimurium ΔaroA strains expressing the C. jejuni antigen CjaA. We evaluated an attenuated avian pathogenic E. coli (APEC) expressing CjaA as a TetC fusion, or TetC, relative to S. Typhimurium ΔaroA expressing the same antigens. APEC have lower zoonotic potential and a commercially available APEC vaccine (PoulVac® E. coli) is used to control avian colibacillosis. In a single trial, neither vaccine decreased caecal Campylobacter levels compared to mock-vaccinated controls, though antigen-specific humoral responses were detected. To screen other candidate antigens, the surface-localised and immunogenic Campylobacter proteins PorA, FspA1, CjaA, FliD and FlgE2 were cloned, expressed, purified as GST fusions and evaluated as subunit vaccines in chickens. Although decreases in caecal Campylobacter counts of up to 1.5 log10 CFU/g were observed in the CjaA and FliD groups at various time points, they were not statistically significant different from controls. Six other candidates have been cloned, expressed and purified and further trials will assess their protective efficacy and seek to reproduce protective effects observed with CjaA and FliD.
    17th International Workshop on Campylobacter, Helicobacter and Related Organisms (CHRO) 2013, Aberdeen, UK; 09/2013
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    Dataset: ng.2657-S1

Publication Stats

4k Citations
449.66 Total Impact Points

Institutions

  • 2010–2015
    • The University of Edinburgh
      • • Royal (Dick) School of Veterinary Studies
      • • Roslin Institute
      Edinburgh, Scotland, United Kingdom
    • University of Queensland
      Brisbane, Queensland, Australia
  • 2013
    • The Roslin Institute
      Edinburgh, Scotland, United Kingdom
  • 1998–2012
    • Institute for Animal Health
      • Department of Immunology
      United Kingdom
  • 2006–2009
    • Iowa State University
      • Department of Animal Science
      Ames, IA, United States
    • Royal Veterinary College
      • Department of Pathology and Infectious Diseases
      London, ENG, United Kingdom
  • 1999–2009
    • Biotechnology and Biological Sciences Research Council
      Swindon, England, United Kingdom
  • 2008
    • Imperial College London
      • Section of Leukocyte Biology
      Londinium, England, United Kingdom
    • Southern University Agricultural Research and Extension Center
      Baton Rouge, Louisiana, United States
  • 2003–2005
    • Texas A&M University
      • Department of Poultry Science
      College Station, Texas, United States