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Functional characterization of selected meningococcal autotransporter proteins

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

Project Description

Neisseria meningitidis (meningococcus) is a Gram-negative human nasopharyngeal commensal which can cause rapidly progressing septicaemia and meningitis. Meningococci elaborate numerous cell-surface and secreted virulence factors which facilitate colonization of, persistence in, and damage to, the host. One important class are the autotransporter (or type V secreted) proteins. Eight autotransporter proteins have been identified in meningococci, five of which were first discovered in our laboratory. Our current focus is on the App, MspA and NalP autotransporters. These are secreted proteases which cleave various host cell proteins and/or bacterial surface proteins, but their full repertoire of targets and activities, and thus precisely how they contribute to pathogenicity are still unclear. We aim to investigate phase-variable expression states, host cell receptors, uptake pathways, proteolytic targets, signalling events and phenotypic changes mediated by the autotransporters to provide new insights into pathogenesis. Projects investigating these various aspects of meningococcal autotransporter biology will provide training in tissue culture, advanced microscopy, flow cytometry, protein biochemistry and molecular microbiology.

Funding Notes

Home and EU applicants should contact the supervisor to determine the current funding status for this project. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University http://www.nottingham.ac.uk/studywithus/international-applicants/scholarships-fees-and-finance/scholarships/index.aspx .

References

Khairalla A, Omer SA, Mahdavi J, Aslam A, Dufailu OA, Self T, Jonsson A-B, Geörg M, Sjölinder H, Royer P-J, Martinez-Pomares L, Ghaemmaghami AM, Wooldridge KG, Oldfield NJ, Ala'Aldeen DAA (2015) Nuclear trafficking, histone cleavage and induction of apoptosis by the meningococcal App and MspA autotransporters. Cell Microbiol doi: 10.1111/cmi.12417.
Oldfield NJ, Matar S, Bidmos FA, Alamro M, Neal KR, Turner DPJ, Bayliss CD, Ala’Aldeen DAA (2013) Prevalence and phase variable expression status of two autotransporters, NalP and MspA, in carriage and disease isolates of Neisseria meningitidis. PLoS One 8: e69746.
Benz I, Schmidt MA (2011) Structures and functions of autotransporter proteins in microbial pathogens. Int J Med Microbiol 301:461-468.

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