About the Project
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. Although the clinical picture is well-established, little is known about the infection biology of iNTS pathogens because of the lack of basic research on this neglected infection.
Comprehensive phylogenomic analyses have identified a novel African clade of S. Typhimurium, ST313 associated with iNTS disease (Kingsley et al., 2009). All African S. Typhimurium ST313 isolates carry a characteristic accessory genome that includes distinct plasmids, and the phages BTP1 and BTP5 (Owen et al., 2017). BTP1 is capable of modifying the LPS of S. Typhimurium via the GtrC acetyltransferases (Kintz et al., 2015).
We have recently discovered that the S. Typhimurium ST313 isolates responsible for the African iNTS epidemic are closely related to ST313 strains that are currently causing gastroenteritis in the UK (Ashton et al., unpublished).
This project will involve the construction of hybrid versions of the UK strains that carry components of the accessory genome of the African isolates. We will use a genetic approach to introduce phages and plasmids from African Salmonella isolates into the UK ST313 strains.
Subsequently, extensive phenotypic and transcriptomic analyses will be used to screen for fitness benefits associated with particular components of the accessory genome. The results will be used to devise a series of experiments to address the mechanistic differences that differentiate the invasive African strains from European gastroenteritis strains.
The information will be used to understand the process of evolution that culminated in the arisal of virulent S. Typhimurium strains in Africa, and could lead to novel therapeutic approaches.
This position will suit an enthusiastic Ph.D. student with an interest in Salmonella infection, functional genomics and gene regulation.
The project will be led by Jay Hinton, the Professor of Microbial Pathogenesis in the Institute of Integrative Biology, University of Liverpool.
We will provide a thorough training in the use of functional genomics to study bacterial pathogenesis. The successful applicant will gain experience in many aspects of molecular microbiology, including bacterial genetics, molecular biology, computational biology and infection biology.
Applicants should have at least a First or Upper Second class B. Sc. Honours degree that includes a significant component of molecular microbiology. Prior laboratory experience that involved Salmonella genetics would be an advantage.
Funding Notes
The Institute of Integrative Biology offers competitive IIB International Scholarships. These cover tuition and research fees and a one-off sum of £1000 will be provided on commencement of studies but students must provide all their living costs for the duration of their studies.
Applicants must be able to commence studies 1 October 2017.
All applications must be made before 26 May 2017 using the University of Liverpool on-line system at https://www.liverpool.ac.uk/study/postgraduate-research/how-to-apply/ for Full Time PhD Biological Sciences for term 2017-18.
Interviews will be held during June with applicants notified of the outcome by 30 June 2017.
References
Kingsley, R. A., C. L. Msefula, N. R. Thomson, S. Kariuki, K. E. Holt, M. A. Gordon, D. Harris, L. Clarke, S. Whitehead, V. Sangal, K. Marsh, M. Achtman, M. E. Molyneux, M. Cormican, J. Parkhill, C. A. MacLennan, R. S. Heyderman & G. Dougan, (2009) Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome research 19: 2279-2287.
Kintz E, Davies MR, Hammarlöf DL, Canals R, Hinton JC, van der Woude MW (2015) A BTP1 prophage gene present in invasive non-typhoidal Salmonella determines composition and length of the O-antigen of the lipopolysaccharide. Mol Microbiol. 96: 263-75. doi: 10.1111/mmi.12933.
Owen SV, Wenner N, Canals R, Makumi A, Hammarlöf DL, Aertsen A, Feasey NA Hinton JC (2017) Characterization of the Prophage Repertoire of African Salmonella Typhimurium ST313 Reveals High Levels of Spontaneous Induction of Novel Phage BTP1. Frontiers Microbiology 8: 235. doi: 10.3389/fmicb.2017.00235.