fosters

Prof Simon Foster

Room: F18a
0114 222 4411
s.foster@sheffield.ac.uk

General

Career History

  • 1999 - present: Professor of Molecular Microbiology, University of Sheffield
  • 1993 - 2002: Royal Society University Research Fellow, University of Sheffield
  • 1990 - 1993: J.G.Graves Medical Research Fellow, University of Sheffield
  • 1986 - 1990: Broodbank Fellow, University of Cambridge
  • 1984 - 1986: PhD, University of Cambridge
  • 1983 - 1984: PhD, University of Leeds
  • 1980 - 1983: BSc Microbiology, University of Liverpool

Research Keywords

Microbiology, Staphylococcus aureus, pathogenicity, cell wall structure

Research

Research in my laboratory centres on 2 main themes associated with bacterial molecular physiology:

The pathogen Staphylococcus aureus
S. aureus is a major cause of death and disease in humans. The spread of antibiotic resistance (MRSA, VRSA) highlights its importance. Our research has taken a number of approaches to understand the pathogenesis of the organism and to develop new prophylactic and treatment regimes. Research is aimed at determining how S. aureus interacts with its host. In particular we have been determining the role of human innate defences in the control of S. aureus. We have also identified a number of potential novel targets to be exploited as vaccine components. The role and use of these for prophylaxis are the subject of current investigations.

fig1Host-pathogen interaction: Fluorescently labelled S. aureus (yellow and blue) have been phagocytosed by a host macrophage. Scale bar 10μm.

Bacterial cell wall structure and function
The cell wall peptidoglycan is essential for the life of most bacteria and its synthesis is the target of such important antibiotics as penicillin and vancomycin. We are using atomic force microscopy and other super-resolution microscopy techniques to determine the architecture and dynamics of peptidoglycan across the bacteria. This has revealed a hitherto unexpected complexity leading to new models of cell wall growth and division.


fig2

Bacterial cell wall architecture: Atomic force microscopy reveals new features of bacterial cell wall peptidoglycan architecture during growth and division. Scale bar 0.5 μm.

fig3

Bacterial cell wall synthesis: Pattern of cell wall peptidoglycan synthesis as revealed by fluorescent vancomycin labelling and super-resolution fluoresence microscopy. A,C, Stochastic optical reconstruction microscopy (STORM); B, Structured illumination microscopy (SIM). Bar 0.5μm.

Teaching

Module Coordinator: MBB323 Microbial Structure and Dynamics: Genes and Populations

Level 3 Modules

Level 2 Modules

Level 1 Modules

PhD Opportunities

I welcome applications from prospective home / EU PhD students for two fully funded PhD studentships: see details below. The third one is available to home, EU or overseas applicants.

You can apply for a PhD position in MBB here.

Contact me at s.foster@sheffield.ac.uk for further information.


Seeing is believing: Observing bacterial biofilm formation in vivo - FULLY FUNDED

Most bacteria grow as biofilms in their natural environment. This is particularly important for pathogens such as Staphylococcus aureus, which is notorious for growing on implants such as joint replacements. Such biofilms are extremely difficult to treat with antibiotics and often means the implant needs to be removed. The project will bring together state-of-the-art imaging approaches to determnine how biofilms are made during an infection. The zebrafish embryo model of S. aureus pathogenesis is unique to Sheffield and offers a window on disease, as the embryos are transparent. The project will visualise biofilm formation in vivo using a combination of fluorescent labelling of bacteria and real-time microscopy to determine components important in biofilm formation and how they are expressed. The action of antimicrobial interventions will be visualised in vivo using the zebrafish model. The experiments will be used to inform apporaches for understanding and controlling biofilm formation in mammals by such an important antimicrobial resistant pathogen as S. aureus.

Relevant publications:

J. Garcia-Lara et al (2015) Supramolecular structure in the membrane of Staphylococcus aureus. Proc Natl Acad Sci USA 112, 15725-15730.

T. K. Prajsnar et al (2012) A privileged intraphagocyte niche is responsible for disseminated infection of Staphylococcus aureus in a zebrafish model. Cellular Microbiology 14, 1600-1619.

This project is supervised by Prof Foster, Prof Stephen Renshaw (Dept of Biomedical Science, University of Sheffield) and Prof Ken Bayles (Medical Center, University of Nebraska, USA) and the student will spend some time in Prof Bayles' lab during the project.

This PhD studentship is funded by the BBSRC White Rose DTP.

Nanoscale mapping of the bacterial surface - FULLY FUNDED

This Sheffield based project will seek to determine how S. aureus is able bind to the human host using an array of surface proteins. We will use an interdisciplinary approach combining genetics, microbiology, state-of-the-art super resolution microscopy and biophysical techniques to analyze the organisation and dynamics of surface adhesins in S. aureus, in order to define the mechanisms underpinning adhesion and the formation of biofilms.

Objectives
1. Generation of a molecular toolbox
Genetic constructs to allow fluorescence microscopy analysis of surface protein localization will be made.
2. Molecular resolution of surface component organization
Surface proteins will be localized at molecular resolution using a combination of structured illumination and stochastic optical reconstruction microscopy (STORM) approaches. A parallel approach using specific antibodies to the surface proteins and labeling with fluorescent or gold particles followed by STORM or atomic force microscopy will provide an alternative strategy for localization.
3. Protein localization dynamics
The role of environmental and genetic factors will be determined to understand how surface protein dynamics is controlled in response to the changing environment of the host and in the presence of interventions such as antibiotics.

Training provision for student
The student will receive a truly interdisciplinary training with a microbiologist and physicist as supervisors. All necessary techniques to be carried out during the project are already available within the laboratories including super resolution microscopy (http://www.imagine-imaginglife.com/).

The studentship is supervised jointly by Prof Simon Foster and Prof Mark Leake (University of York). It is a 4-year studentship and is part of a White Rose Studentship Network.









































Publications

Journal articles

Conference proceedings papers

  • Anwar S, Prince LR, Sabroe I, Foster SJ & Whyte MK (2007) Subversion of neutrophil apoptosis by Staphylococcus aureus. THORAX, Vol. 62 (pp A114-A115)
  • Agren J, Foster SJ, Thiemermann C, Wang JE & Aasen AO (2005) Synthetic CpG- and GpC oligonucleotides enhance the TNF alpha release induced by peptidoglycan but not by lipopolysaccharide.. SHOCK, Vol. 23 (pp 22-22)
  • Hadley JS, Wang JE, Foster SJ, Thiemermann C & Hinds CJ (2004) Cytokine responses to combined administration of lipopolysaccharide (LPS) and peptidoglycan (PepG). SHOCK, Vol. 21 (pp 50-50)