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Investigating the interaction of Neisseria meningitidis with cells of its human host

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  • Full or part time
    Dr Woodridge
    Dr Oldfield
  • 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. A number of host cell-surface receptors have been identified that are engaged by the meningococcus. This engagement leads to adhesion of the bacterium to the cell surface, thus helping establish the meningococcus in its niche, and also leads to a two-way cellular communication between the bacterium and host cell. We have identified the human cell-surface proteins laminin receptor and galectin-3 as important receptors for the meningococcus, as well as other important meningeal pathogens. Engagement of these receptors by the bacterium leads to changes in the biology of the host cell in ways that might favour the bacterium’s continual survival but the detailed molecular events occurring in response to this interaction remain to be elucidated. We plan to characterise these events, as well as investigating the potential therapeutic effect of a meningococcal surface peptide that interacts with laminin receptor in the treatment of non-infectious diseases involving this receptor. PhD projects are available to focus on aspects of these interactions; students will receive training in tissue culture, confocal and advanced microscopy, handling of ACDP hazard group 2 pathogens, 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 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

Deciphering the complex three-way interaction between the non-integrin laminin receptor, galectin-3 and Neisseria meningitidis.
Alqahtani F, Mahdavi J, Wheldon LM, Vassey M, Pirinccioglu N, Royer PJ, Qarani SM, Morroll S, Stoof J, Holliday ND, Teo SY, Oldfield NJ, Wooldridge KG, Ala'Aldeen DA.
Open Biol. 2014 Oct;4(10). pii: 140053. doi: 10.1098/rsob.140053. PMID: 25274119
Deciphering the contribution of human meningothelial cells to the inflammatory and antimicrobial response at the meninges.
Royer PJ, Rogers AJ, Wooldridge KG, Tighe P, Mahdavi J, Rittig MG, Ala'Aldeen D.
Infect Immun. 2013 Nov;81(11):4299-310. doi: 10.1128/IAI.00477-13. Epub 2013 Sep 3. PMID: 24002066
Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2.
Abouseada NM, Assafi MS, Mahdavi J, Oldfield NJ, Wheldon LM, Wooldridge KG, Ala'Aldeen DA.
PLoS One. 2012;7(9):e46233. doi: 10.1371/journal.pone.0046233. Epub 2012 Sep 25. PMID:23049988
Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models.
Orihuela CJ, Mahdavi J, Thornton J, Mann B, Wooldridge KG, Abouseada N, Oldfield NJ, Self T, Ala'Aldeen DA, Tuomanen EI.
J Clin Invest. 2009 Jun;119(6):1638-46. doi: 10.1172/JCI36759. Epub 2009 May 11.
PMID: 19436113

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FTE Category A staff submitted: 90.86

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