Explore the impact of genetic variation on the livestock immune response to pathogens
Lead Research Organisation:
The Pirbright Institute
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
This project aims to advance our understanding of the functional impact of genetic variation on the immune response of livestock, with particular emphasis on innate immune responses. The knowledge gained will enable a more accurate assessment of the interplay between different arms of the immune system through their effector cells during infection and vaccination. Advances in sequencing technology and analysis now provide the opportunity decipher genetic variation at the level of the genome and transcriptome at high resolution. These data facilitate the interrogation of specific immune components in vitro and in vivo to resolve their function and importance during particular pathogen infections. This project will use these methods to provide a basis for identifying gene variants that are beneficial or detrimental to the host during infection, a greater understanding of the molecular mechanisms that govern the immune response and better define potential correlates of protection.
Planned Impact
unavailable
Organisations
- The Pirbright Institute (Lead Research Organisation)
- UNIVERSITY OF EDINBURGH (Collaboration)
- University of Glasgow (Collaboration)
- U.S. Department of Agriculture USDA (Collaboration)
- Norwegian School of Veterinary Science (Collaboration)
- International Livestock Research Institute (ILRI) (Collaboration)
- Stanford University (Collaboration)
- Texas A&M University-Central Texas (Collaboration)
- University of Warwick (Collaboration)
- ANTHONY NOLAN (Collaboration)
People |
ORCID iD |
| John Hammond (Principal Investigator) |
Publications
Allan AJ
(2015)
Cattle NK Cell Heterogeneity and the Influence of MHC Class I.
in Journal of immunology (Baltimore, Md. : 1950)
Ballingall KT
(2018)
Comparative MHC nomenclature: report from the ISAG/IUIS-VIC committee 2018.
in Immunogenetics
Bickhart DM
(2017)
Single-molecule sequencing and chromatin conformation capture enable de novo reference assembly of the domestic goat genome.
in Nature genetics
Browning HM
(2015)
Common cancer in a wild animal: the California sea lion (Zalophus californianus) as an emerging model for carcinogenesis.
in Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Browning HM
(2014)
Evidence for a genetic basis of urogenital carcinoma in the wild California sea lion.
in Proceedings. Biological sciences
Bruijnesteijn J
(2020)
Nomenclature report for killer-cell immunoglobulin-like receptors (KIR) in macaque species: new genes/alleles, renaming recombinant entities and IPD-NHKIR updates.
in Immunogenetics
Connelley TK
(2014)
NKp46+ CD3+ cells: a novel nonconventional T cell subset in cattle exhibiting both NK cell and T cell features.
in Journal of immunology (Baltimore, Md. : 1950)
De Groot NG
(2020)
Nomenclature report 2019: major histocompatibility complex genes and alleles of Great and Small Ape and Old and New World monkey species.
in Immunogenetics
Dorey-Robinson D
(2023)
IgMAT: immunoglobulin sequence multi-species annotation tool for any species including those with incomplete antibody annotation or unusual characteristics.
in BMC bioinformatics
Ellis SA
(2014)
The functional significance of cattle major histocompatibility complex class I genetic diversity.
in Annual review of animal biosciences
| Description | We have assembled the first complete MHC class I haplotype from cattle that is being used for genetic mapping as the break points in the genome where genes are rearranged have no been pinpointed. We have significantly extended our ability to annotate the immune genes in ruminant genomes, and are currently working with sheep, goats and cattle as well as the non-ruminant species, the pig. These regions are notoriously hard to assemble and annotate and this data is being used to underpin the development of assay to properly quantify relative gene expression during infection and vaccination. Methods to sequence and analyze the cattle antigen specific response to vaccination and infection with FMDV have also been developed. This has in turn led us to understand the unique way that cattle antibodies are formed and expand in vivo to challenge. |
| Exploitation Route | The bioinformatic approaches we have developed are applicable across species and antigens. Understanding the antibody response helps us to define how protection occurs after vaccination or infection. This can be fed into vaccine design and testing. |
| Sectors | Agriculture Food and Drink |
| Description | Our methodological approaches are being adopted by others to explore the antibody repertoire in response to different infections in other species. These findings have also underpinned successful applied research funding. We have also been able to use the skills in genome annotaion that we have aquired to underpin the annotation of new livestock genomes that are being sequenced to ensure accuracy before they are made public. |
| First Year Of Impact | 2014 |
| Sector | Agriculture, Food and Drink |
| Description | BBSRC GCRF Databases and Resources |
| Amount | £1,400,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 06/2018 |
| Description | BBSRC GCRF Databases and Resources |
| Amount | £730,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2017 |
| End | 08/2019 |
| Description | BBSRC IAA, "Generating high-quality reference of the Babraham pig." |
| Amount | £44,075 (GBP) |
| Funding ID | BB/S506680/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2018 |
| End | 05/2020 |
| Description | Pirbright Agri-Food Technology Seed Fund |
| Amount | £23,568 (GBP) |
| Organisation | The Pirbright Institute |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2018 |
| End | 01/2019 |
| Description | The impact of natural genetic variation on ruminant immune responses |
| Amount | £80,000 (GBP) |
| Organisation | University of Southampton |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 09/2018 |
| End | 09/2022 |
| Description | Wellcome Trust Strategic award |
| Amount | £2,433,971 (GBP) |
| Organisation | Wellcome Trust |
| Department | Wellcome Trust Institutional Strategic Support Fund |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2014 |
| End | 03/2017 |
| Title | Genome enrichement with long read sequencing |
| Description | We have developed the Nimblegen-Roche SeqCapEZ probes based pull down method to work with genomic DNA fragments up to 6kb in length with PacBio sequencing. This is being used for de novo assembly of variable regions |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2018 |
| Provided To Others? | No |
| Impact | We are now involved with industry to refine this protocol further with less input DNA and high multiplex capability. |
| Description | Anne Storset |
| Organisation | Norwegian School of Veterinary Science |
| Country | Norway |
| Sector | Academic/University |
| PI Contribution | Informing current immunological studies about the NK cell diversity they are studying |
| Collaborator Contribution | Providing immunological data and antibodies for current and future studies |
| Impact | None yet |
| Start Year | 2014 |
| Description | Bridget Penman |
| Organisation | University of Warwick |
| Department | School of Life Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are providing genetic data and diversity measures of MHC and associated receptors to inform the modelling efforts to elucidate which selection pressures are the main drivers for the types of diversity we see in extant species. |
| Collaborator Contribution | They are experts in mathmatical modelling and will provide data to help explain genetic diversity in cattle. |
| Impact | Not yet |
| Start Year | 2017 |
| Description | Derek Bickhart-USDA |
| Organisation | U.S. Department of Agriculture USDA |
| Department | Beltsville Agricultural Research Center |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Our group has provided the genomic framework of the cattle NK cell regions and the biological input. |
| Collaborator Contribution | The ARS group has used our data as a framework to map and predict cattle SNPs for variable immune traits using their whole genome data |
| Impact | Research application based on preliminary data to a BBSRC-NIFA call. This collaboration is multi-disciplinary combining molecular biology and computational biology |
| Start Year | 2014 |
| Description | Glasgow |
| Organisation | University of Glasgow |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are providing diverse genetic data and molecular interaction data leading to immune functional variation. We are also working with diverse viral sequences and providing sequence data and analysis of attenuated viral populations and functional outputs. |
| Collaborator Contribution | This group is putting this data into a new mathematical model to analyze biological diversity and evolutionary patterns. Using our virus data they are using their analytical framework for RNA virus population analysis that has been developed at Glasgow, as a comparison to our analysis with different viruses. |
| Impact | The collaboration is multi-disciplinary involving molecular biology and genetics with mathematical modelling |
| Start Year | 2012 |
| Description | ILRI Research Collaboration (Kenya, March 2017) |
| Organisation | International Livestock Research Institute (ILRI) |
| Country | Kenya |
| Sector | Charity/Non Profit |
| PI Contribution | Exchange of ideas and samples for indigenous breeds of livestock |
| Collaborator Contribution | Contributed samples for analysis. |
| Impact | Analysis of indigenous breed genomic sequences for Immune function genes. |
| Start Year | 2017 |
| Description | Loren Skow, Texas A&M |
| Organisation | Texas A&M University-Central Texas |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We are sequencing extended MHC haplotypes from cattle samples that have previously been typed by low resolution SNPs |
| Collaborator Contribution | Providing samples and SNP data for animals with known phenotypes. |
| Impact | Not yet |
| Start Year | 2017 |
| Description | Parham Lab at Stanford |
| Organisation | Stanford University |
| Department | School of Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Our group designed the experiments and generated a majority of the data. We also led the analysis of the data and writing of the manuscripts |
| Collaborator Contribution | The Parham lab is the leading group worldwide in the evolutionary study of NK cell receptors and MHC class I. This group generated part of the data and helped in the analysis, interpretation and manuscript preparation |
| Impact | Definition of the Cattle Killer Cell Igndash like Receptor Gene Family: Comparison with Aurochs and Human Counterparts Nicholas D. Sanderson, Paul J. Norman, Lisbeth A. Guethlein, Shirley Ellis, Christina Williams, Matthew Breen, Steven D. E. Park, David A. Magee, Farbod Babrzadeh, Andrew Warry, Mick Watson, Daniel G. Bradley, David E. MacHugh, Peter Parham, and John A. Hammond. Journal of Immunology, Dec 15, 2014; 193 (12) This collaboration is not multi-didciplinary |
| Start Year | 2009 |
| Description | The Anthony Nolan |
| Organisation | Anthony Nolan |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Providing data contributing to the maintenance and curation of IPD-MHC databases |
| Collaborator Contribution | Incorporating our data into IPD-MHC |
| Impact | This collaboration is not multi-disciplinary. The main output so far is the cattle section on IPD-MHC |
| Start Year | 2012 |
| Description | The Roslin Institute |
| Organisation | University of Edinburgh |
| Department | The Roslin Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have been working with several groups using our molecular and genetic data to help understand cattle cellular immunology. We have also hosted a visiting scientist to provide training in molecular techniques and data analysis, This has continued and now includes members of the Centre for Tropical Livestock Health and Genetics where we are engaged in sample sharing and maximising the value of genetic data by linking different sources as much as possible. |
| Collaborator Contribution | Our partners have provided data and reagents as well as intellectual input to help us translate genetic diversity into functional diversity |
| Impact | This collaboration is multi-disciplinary, although largely immunology and associated genetics is also involves bioinformatics |
| Start Year | 2011 |
| Description | Guest lecture at Southampton University |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | Very interactive discussions and stimulated wider interest in genomics amongst undergraduate students None to date except being asked to continue delivering this lecture |
| Year(s) Of Engagement Activity | 2013,2014 |
| Description | ISAG 2017 - Comparison of the cattle leukocyte receptor complex with related livestock species |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Discussed our current research |
| Year(s) Of Engagement Activity | 2017 |
| Description | Immunogenetics Workshop at ILRI, Nairobi - The evolution and diversity of NK cell receptors in livestock species |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Discussed our current research |
| Year(s) Of Engagement Activity | 2017 |
| Description | Internal Seminar - The evolution and diversity of natural killer cell receptors in bovids. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Presented our current research and received audience feedback |
| Year(s) Of Engagement Activity | 2018 |
| Description | Internal seminar - Use of long-read sequencing to resolve complex genomic regions |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Discussed our current research |
| Year(s) Of Engagement Activity | 2017 |
| Description | KIR 2017 Workshop - Comparison of the cattle leukocyte receptor complex with related livestock species |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Discussed our current research |
| Year(s) Of Engagement Activity | 2017 |
| Description | LEAF Open Farm Sunday |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Public engagement at a local farm to describe our research and relevance to the public. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Oral presentation - 2019 PAG meeting - Contiguity of the Goat Genome Assembly Enables Comparative Analyses and Gene Discovery within the Repetitive Immune-Related Regions. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Discussed our current research and received audience feedback |
| Year(s) Of Engagement Activity | 2019 |
| Description | Oral presentation - KIR meeting 2018 - Goat and sheep KIR have independently expanded compared to cattle and a unique subtype is unusually expressed |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Presented current research and received audience feedback |
| Year(s) Of Engagement Activity | 2018 |
| Description | Outreach at Fox Corner Community Wildlife Area |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Local community outreach event in which we volunteered to clear invasive plant species |
| Year(s) Of Engagement Activity | 2017 |
| Description | PacBio Leiden |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Presented data to academics and industry experts on the methods we have developed to enrich and sequence targeted areas of genomes |
| Year(s) Of Engagement Activity | 2018 |
| Description | Presentation to UKRI chair and Trustee Board |
| 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 | Policymakers/politicians |
| Results and Impact | Presentation of latest research in livestock immunogenetic diversity to UKRI chair and Trustee Board members. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Public Open Day at Diamond Light Source |
| 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 | Staffed The Pirbright Institute's booth at Diamond Light Source's Public Open Day in July 2017. Described our current research to the general public. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Science update to BBSRC executives |
| 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 | Policymakers/politicians |
| Results and Impact | Presentation of our latest research in livestock immunogenetic diversity to visiting BBSRC executives at The Pirbright Institute. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Southampton Lecture |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | Lectures on Genomic Immunology and Food Security as part of an undergraduate course to molecular biologists |
| Year(s) Of Engagement Activity | 2015,2016,2017 |
| Description | conference seminar - cattle NKC at 2015 KIR Workshop |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Discussed our current research |
| Year(s) Of Engagement Activity | 2015 |
| Description | internal seminar - NKC evolution |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Conveyed and discussed our current research to peers at The Pirbright Institute. |
| Year(s) Of Engagement Activity | 2016 |
| Description | internal seminar - sequencing immune gene complexes |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Presented an introduction to our current research |
| Year(s) Of Engagement Activity | 2017 |
| Description | invited seminar - NKC and LRC co-evolution - University of Minnesota |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Discussed our current research |
| Year(s) Of Engagement Activity | 2016 |
| Description | invited seminar - NKC evolution - UFMG, Brazil |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Discussed current research at UFMG Vet School in Belo Horizonte, Brazil |
| Year(s) Of Engagement Activity | 2016 |
| Description | invited seminar - sequencing immune gene complexes - University of Minnesota |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Discussed current work using new reference genomes to characterise immune gene complexes |
| Year(s) Of Engagement Activity | 2016 |