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Are farm animal-associated Salmonella hyper-susceptible to bacteriophage killing?

  • Full or part time
  • Application Deadline
    Friday, January 11, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a bacterial pathogen that generally causes gastroenteritis in humans. iNTS (invasive non-typhoidal salmonellosis) has recently been found to be responsible for epidemics of bloodstream infection. The clinical syndrome presents with septicaemia and is associated with high morbidity and mortality, killing 388,000 people annually in Africa. It has recently been discovered that, in Africa, different Salmonella serovars infect humans and farm animals. We hypothesise that farm animal-associated Salmonella rarely infect humans because they are susceptible to phage infection.

We have recently discovered that the human pathogen S. Typhimurium ST313 carries a novel phage immunity system that protects the pathogenic bacteria from predation by bacteriophage. This project will investigate whether farm animal-associated Salmonella from Africa have an alternative immunity system to protect them from phage killing, or whether they are hyper-sensitive to phage infection.

This project will begin with a detailed bioinformatic analysis of 5000 African Salmonella Genomes to determine the prevalence of the BstA system in human-associated and farm animal-associated Salmonella. Next, we will determine whether farm animal-associated Salmonella that lack the BstA system are hyper-sensitive to phage infection, using a bank of bacteriophages that have already been isolated from river water in the UK and in Africa (in a collaborative project involving the two project supervisors). To investigate the ecological implications of differences in phage susceptibility between human-associated and farm animal-associated Salmonella, competition experiments will be conducted. Finally, we will use a molecular genetic approach to determine whether the BstA system will protect food-associated Salmonella from bacteriophage killing.

This position will suit an enthusiastic Ph.D. student with an interest in Salmonella, genomics, phage biology and bioinformatics. The project will be led by Jay Hinton, the Professor of Microbial Pathogenesis in the Institute of Integrative Biology, University of Liverpool, and co-supervised by Dr Tim Blower from the Biosciences Department of Durham University.

We will provide a thorough training in the use of bioinformatics to analyse bacterial genomes. The successful applicant will also gain experience in many aspects of molecular microbiology, including bacterial genetics and phage biology.

For further information see the website: https://www.liverpool.ac.uk/integrative-biology/

To apply

Please complete the online application form and attach a full CV and covering letter. Informal enquiries may be made to

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,777 for 2018-19). The PhD will start in October 2019. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. There are 2 stages to the application process.

References

Hammarlöf DL, Kröger C, Owen SV, Canals R, Lacharme-Lora, Wenner N, Schager AE, Wells TJ, Henderson IR, Wigley P, Hokamp K, Feasey NA, Gordon MA, Hinton JCD (2018) Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella. PNAS pii: 201714718 DOI: 10.1073/pnas.1714718115

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