Imperial College London Featured PhD Programmes
Coventry University Featured PhD Programmes
University of Reading Featured PhD Programmes

Role of metabolism-related islets in Salmonella pathogenesis & zoonotic risk


Project Description

Supervisors: Professor Mark Stevens & Dr Prerna Vohra (University of Edinburgh) and Professor Andrew Roe (University of Glasgow).

Salmonella enterica is an animal and zoonotic pathogen of global importance. An estimated 78 million cases of human nontyphoidal salmonellosis occur annually, causing the loss of 59k lives and 4.1m disability-adjusted life years. Such infections are frequently acquired via the food chain from farmed animals. Enteric and systemic salmonellosis also constrains animal productivity and welfare. A need exists for more effective vaccines to control Salmonella in farmed animals. Toward this aim, we have used transposon-directed insertion-site sequencing to assign roles to thousands of Salmonella enterica serovar Typhimurium genes in intestinal colonisation of chickens, pigs and cattle [1, 2]. These studies identified a core subset of genes that play conserved roles across species, but also identified host- and niche-specific virulence factors. Many attenuating mutations were located in islets of metabolism-related genes of poorly defined function. Variation in metabolism-related genes has also been associated with the host tropism and invasive potential of Salmonella.

In this studentship we propose to:
1. Generate mutations in metabolism-related islets implicated in Salmonella pathogenesis.
2. Define the impact of such mutations on the metabolome of Salmonella by mass spectrometry.
3. Characterise mutant phenotypes in vitro, for example in relation to use of specific metabolites and using cell-based assays of virulence-associated phenotypes.
4. Use novel 3R methods to assign phenotypes to mutants in farm animals, for example using ligated intestinal loop models to quantify net replication, inflammation and secretory responses.
5. Use computational approaches to study the relationship between metabolism-related islets and the differential tropism and virulence of S. Typhimurium pathovariants and S. enterica serovars.

The project will harness expertise, datasets and techniques in both partner institutions. Professor Stevens has used award-winning 3R models to study Salmonella virulence with minimal animal use, including by assigning spatiotemporal phenotypes of strains screened in pools [1-4] and via use of surgical models to study the mode and genetics of systemic translocation [4] and Salmonella-induced secretory and inflammatory responses [5]. The proposed studentship aligns closely with the One Health ethos of the programme given the potential to combat an important zoonosis and owing to the similar pathology of enteric salmonellosis in humans, pigs and calves. The project has the potential to yield novel vaccines or treatments to enhance both food safety and animal health. Professor Roe has identified metabolic pathways that regulate virulence in the enteric pathogen Citrobacter rodentium [6] and established a key role for sensing of host D-serine in pathogenic Escherichia coli [7]. Much scope exists to extend this expertise, and the associated metabolomics capability of the Glasgow Polyomics facility, to study the role of Salmonella metabolism and metabolite sensing in pathogenesis.

Funding Notes

Eligibility:
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement.

Applications:
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to our PGR student team at

When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.

References

[1] Chaudhuri RR et al. 2013. PLoS Genetics 9:e1003456.
[2] Vohra et al. 2019. BMC Genomics 20:20.
[3] Vohra P et al. 2018. Appl Environ Microbiol 284: e02262-17.
[4] Pullinger GD et al. 2010. Microbiol 156:3108-22.
[5] Pullinger GD et al. 2010. Infect Immun 78:372-80.
[6] Connolly JP et al. 2018. Nat Commun 9:4187.
[7] Connolly JP, Roe AJ. 2016. Microb Cell 3:181-184.

Related Subjects

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully





FindAPhD. Copyright 2005-2020
All rights reserved.