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
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.
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.
Informal enquiries are welcomed and should be directed to Maisem Laabei on [email protected]
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.
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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.