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Understanding how mutability facilitates survival of alternating selection and bottlenecks by the major food-borne pathogen Campylobacter jejuni

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Aims. Campylobacter jejuni is a major agent of food-borne gastroenteritis. This pathogen contains multiple hypermutable sequences whose hypermutability enables the bacteria to survive the combined effects of fluctuating selection and non-selective bottlenecks. This project will improve our understanding of the pathogenesis and transmission of this important pathogen.

Hypothesis. We hypothesise that the rate of hypermutation is a key determinant for C. jejuni to survive alternating selection by the immune system and bacteriophages.

Experimental methods and research plan. The hypermutable sequences of C. jejuni are mainly polyG tracts (a type of microsatellite) that are highly mutable and whose mutations mediate ON/OFF switches in gene expression. My laboratory has developed a rapid, high through-put analysis method to detect variation in these polyG tracts (Bayliss et al. 2011 and Lango-Scholey et al. 2106) and utilised this assay to characterise the extent of variation in 27 phase-variable genes of C. jejuni strain 11168 during in vitro passage, infections of chickens and after imposition of non-selective bottlenecks (Aidley et al 2016). We have also utilised this method to examine escape of killing by bacteriophage F336 and shown that escape is mainly due to ON/OFF switches in two genes, cj1421 and cj1422, that modify the capsule (Aidley et al 2017). We have unpublished data showing that switches in these genes mediate resistance to killing by human serum so that we can select for one state with phage and the other state with serum and hence have alternating selection. This project will further explore these alternating selection pressures using mutants with altered switching rates, imposition of bottlenecks and with computer modelling.

Funding Notes

This project is offered as part of the Midlands Integrative Biosciences (Doctoral) Training Partnership (MIBTP). This programme is a BBSRC funded doctoral training partnership between the University of Warwick, the University of Birmingham and the University of Leicester.

Further information on this scheme and the application process can be obtained from:-
View Website

For specific information on this project please contact Dr Chris Bayliss at or by phone at 0116 2523465. The other main supervisor for this project will be Dr. Andrey Morozov () from the Department of Mathematics.

References

Aidley J, Sørensen MCH, Bayliss CD, Brøndsted L (2017). Phage exposure causes dynamic shifts in the expression states of specific phase-variable genes of Campylobacter jejuni. Microbiology. 163:911-919. PMID: 28597819

Aidley J, Rajopadhye S, Akinyemi NM, Lango-Scholey L, Bayliss CD. (2017). Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations. MBio. 8. pii: e02311-16.

Lango-Scholey L, Aidley J, Woodacre A, Jones MA, Bayliss CD. (2016) High Throughput Method for Analysis of Repeat Number for 28 Phase Variable Loci of Campylobacter jejuni Strain NCTC11168. PLoS One. 2016 Jul 28;11(7):e0159634.

Bayliss CD, Bidmos FA, Anjum A, Manchev VT, Richards RL, Grossier JP, Wooldridge KG, Ketley JM, Barrow PA, Jones MA, Tretyakov MV (2012). Phase variable genes of Campylobacter jejuni exhibit high mutation rates and specific mutational patterns but mutability is not the major determinant of population structure during host colonization. Nucl. Acids Res. 40:5876-89.

How good is research at University of Leicester in Biological Sciences?

FTE Category A staff submitted: 37.40

Research output data provided by the Research Excellence Framework (REF)

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