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Immunogenetics and the carriage of meningococcal bacteria

Primary Supervisor: Dr Bridget Penman, School of Life Sciences

Secondary supervisor: t.b.c.

PhD project title: Immunogenetics and the carriage of meningococcal bacteria

University of Registration: University of Warwick

Project outline:

    Neisseria meningitidis is a bacterium carried in the back of the throat. Most of the time carriage is harmless. However, when N. meningitidis invasive disease occurs, causing meningitis or sepsis, it has an extremely high mortality rate. An important aspect of the ecology and evolution of N. meningitidis which has so far gone unstudied is the relationship between human immune system genes and N. meningitidis carriage.

    Human leukocyte antigen (HLA) genes encode proteins that help T cells recognise pathogens. HLA genes are some of the most diverse in the human genome, and a person’s particular set of HLA genes is part of what makes their immune system unique. This project will investigate whether HLA genotype affects the carriage of N. meningitidis, and the public health implications of any such relationship.

    This project is a collaboration between Dr Bridget Penman’s group at the University of Warwick and Prof Martin Maiden’s group at the University of Oxford. The Penman group is where the student will be hosted and will carry out immunogenetic and epidemiological analyses. Collaboration with the Maiden group will allow access to existing stored throat swab samples from N. meningitidis carriage studies, for which bacterial genomes have already been sequenced. The student will use in silico techniques to select an HLA locus to investigate; type the swab samples for that HLA locus, and analyse the resulting combined dataset of HLA data and bacterial genomic data. The student will also incorporate the results of these analyses into epidemiological models of N. meningitidis carriage. Analysis of these models will provide novel insights into this important pathogen. This project will suit a student who is interested in population genetics, host-pathogen interactions, infectious disease epidemiology and public health.

    Background reading:

    1. MacLennan JM et al . Meningococcal carriage in periods of high and low invasive meningococcal disease incidence in the UK: comparison of UKMenCar1-4 cross-sectional survey results. Lancet Infect Dis. 2021;21(5):677-687. doi: 10.1016/S1473-3099(20)30842-2.

    2. Sanchez-Mazas A. A review of HLA allele and SNP associations with highly prevalent infectious diseases in human populations. Swiss Med Wkly. 2020;150:w20214. doi: 10.4414/smw.2020.20214.

    BBSRC Strategic Research Priority: Understanding the Rules of Life: Immunology, Microbiology & Systems Biology

        Techniques that will be undertaken during the project:

        • In silico prediction of MHC molecule / peptide binding
        • Epidemiological modelling
        • Statistical analysis of immunogenetic/microbial carriage data
        • Bioinformatics techniques to process microbial genomic data
        • Machine learning to analyse combined immunogenetic/microbial genomic data

        Contact: Dr Bridget Penman, University of Warwick