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Global analysis of evasive strategies developed by Staphylococcus aureus to circumvent complement and innate immunity

  • Full or part time
  • Application Deadline
    Sunday, February 24, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Staphylococcus aureus is an important human pathogen responsible for a wide-spectrum of diseases that range from mild superficial skin diseases to life-threatening infections. Central to the success of S. aureus is the possession of a sophisticated arsenal of surface and secreted virulence factors coupled with the ability to evolve antibiotic resistance. A common theme among human pathogens is the ability to manipulate host immune responses preventing detection and or labelling with host components responsible for bacterial eradication, in which the complement system plays a major role.

The evolutionary pressure imposed on S. aureus by host immunity has led to the development of a plethora of immune evasins, which are critical for both colonization and pathogenicity. So far, S. aureus is the bacterial species for which the largest number of complement evasion strategies has been identified.

Despite this extensive knowledge there are several key questions which remain unanswered: A) what is the relative importance of each identified virulence factor to complement evasion, B) what environmental conditions and which genetic regulatory elements facilitate expression, C) is there a clonal-specific expression of these factors. Answering these questions will enhance our understanding of this dynamic host-pathogen interaction and aid in the development of novel therapeutics to combat infection.

PROJECT & OBJECTIVES

The project will involve a deep analysis of host and pathogen, focusing primarily on how S aureus manipulates and evades innate immunity. The key objectives of this PhD project are summarised below:

1) Analysis of complement deposition on genome-sequenced clinical isolates and investigation of the effect of the pathogen ‘secretome’ on inhibiting complement activation

2) Adopting a bioinformatic approach using Genome-wide association studies (GWAS) to identify novel genes and/or mutations associated with immune evasion

3) Determine the predominant known immune evasins involved in resisting complement deposition, phagocytosis and ex vivo blood killing

4) Determining host factors important in the eradication of S aureus using in vitro and in vivo infection models

SUPERVISOR AND LAB

The successful candidate will join the group of Maisem Laabei – for more information on the groups’ research activities please see https://researchportal.bath.ac.uk/en/persons/maisem-laabei and https://www.researchgate.net/profile/Maisem_Laabei

The project will be carried out in collaboration with international experts in the field of complement and innate immunity (Prof Anna Blom, Lund University, Sweden) and Staphylococcal pathogenicity (Dr Ruth Massey, University of Bristol) with potential opportunities to visit these labs during the PhD.

CANDIDATE

Applicants should hold, or expect to obtain, a First Class or high Upper Second Class UK Honours degree (or equivalent qualification gained outside the UK) in a relevant field of biological sciences. Experience working in a microbiology/ immunobiology or molecular biology is preferred but not essential. We are seeking candidates with a strong interest in host-pathogen interactions with motivation to explore and better understand the molecular basis of pathogen immune evasion.

APPLICATIONS

Informal enquiries are welcomed and should be directed to Maisem Laabei on .

Formal applications should be made via the University of Bath’s online application form:
https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-FP02&code2=0013

Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section.

More information about applying for a PhD at Bath may be found here:
http://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/

Anticipated start date: 30 September 2019.

Funding Notes

Candidates applying for this project will be considered for a University Research Studentship which will cover UK/EU tuition fees, a training support fee of £1,000 per annum and a tax-free maintenance allowance at the UKRI Doctoral Stipend rate (£14,777 in 2018-19) for a period of up to 3.5 years.

References

R. J. Gordon and F. D. Lowy, "Pathogenesis of methicillin-resistant Staphylococcus aureus infection," Clin Infect Dis, vol. 46 Suppl 5, pp. S350-9, Jun 1 2008.

M. Recker et al., "Clonal differences in Staphylococcus aureus bacteraemia-associated mortality," Nat Microbiol, vol. 2, no. 10, pp. 1381-1388, Oct 2017.

M. Laabei et al., "Predicting the virulence of MRSA from its genome sequence," Genome Res, vol. 24, no. 5, pp. 839-49, May 2014.

M. Laabei et al., "Evolutionary Trade-Offs Underlie the Multi-faceted Virulence of Staphylococcus aureus," PLoS Biol, vol. 13, no. 9, p. e1002229, 2015.

M. Laabei and R. Massey, "Using functional genomics to decipher the complexity of microbial pathogenicity," Curr Genet, vol. 62, no. 3, pp. 523-5, Aug 2016.

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

FTE Category A staff submitted: 24.50

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

Click here to see the results for all UK universities

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