Using genotype-to-phenotype analyses to identify the genetic determinants of gastroenteritis caused by the food-borne pathogen Campylobacter jejuni

Campylobacter jejuni is the major causative agent of foodborne gastroenteritis across Europe. Contaminated chicken meat is the main source of infections and hence control of this pathogen is critical to food security in the poultry industry.

The three major virulence determinants of C. jejuni are capsule, lipooligosaccharide and flagella. The flagella controls the motility of this bacterial pathogen enabling movement towards nutrients and away from damaging agents. The capsule and lipooligosaccharide mediate resistance to immune effectors, influence adhesive properties and contribute to autoimmune complications of C. jejuni infections. All three structures are decorated with a variety of sugar molecules (glycans). These glycans are highly variable between strains due to differences in gene content and allelic variation. Many of these glycans also vary in structure and presence within strains due to high frequency, reversible switches in gene expression caused by hypermutable sequences and referred to as phase variation.

A vast amount of whole genome sequence data is available for C. jejuni providing a major resource for assessing the contributions of genetic elements to phenotypic behaviours. This project aims to unlock the genomic data to identify genotypic determinants of specific phenotypes as part of a long-term goal of establishing a genetic measure of disease potential.

The specific objectives are:- Objective 1. Examine the phenotypic variability of multiple isolates of a single C. jejuni clonal complex. Objective 2. Construct mutants to associate phenotypic variation with specific genes, allelic variants or phase variation states. Objective 3. Generate genetic probes or immunological reagents to track specific genotypes or phase variation states in epidemiological samples. Objective 4. Mine genome databases to assess the distribution and prevalence of single or combinations of disease-associated genotypic variants.

The specific techniques gained during this project will be immunological assays (e.g. serum bactericidal assays, ELISA, Western blotting), tissue culture (e.g. for measuring adhesion and invasion), infection models (e.g. infection of organ cultures and use of animal models), molecular biology (e.g. PCR, GeneScan, cloning, site-directed mutagenesis) and bioinformatics (e.g. whole genome sequence analysis, association tests).

Eligibility:

UK/EU applicants only.

Entry requirements:

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject.

The University of Leicester English language requirements apply where applicable: https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65

How to apply:

Please refer to the application guidance and apply using the online application link at https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp

Project / Funding Enquiries: [email protected]
Application enquiries to [email protected]