About the Project
Second Supervisor: Professor Joan Geoghegan, University of Birmingham
Excess copper is highly toxic and forms part of the host innate immune system’s antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens.
All bacteria possess mechanisms to resist copper toxicity. The importance of bacterial copper resistance is evidenced by epidemic methicillin resistant Staphylococcus aureus (MRSA) acquisition of additional resistance mechanisms that confer copper-hyper resistance causing increased resistance to killing by macrophages and increased S. aureus infectivity.
Importantly our recent data show that subinhibitory copper functions as a regulatory signal, triggering coordinated transcriptional and metabolic remodelling that potentiates S. aureus fitness in the host. Copper alters expression of antibiotic resistance, virulence and immune evasion factors and alters the interaction of S. aureus with human epithelial cells.
Our hypothesis is that copper acts as an environmental signal to drive differential metabolic and physiological changes to potentiate S. aureus resilience to colonise multiple niches. However, the regulatory mechanisms involved and importance of copper homeostasis in clinical S. aureus carriage and disease isolates is unknown.
Aim is to:
- Identify the regulatory mechanisms critical for increased colonisation and antibiotic resistance.
- Determine importance of copper homeostasis mechanisms for clinical S. aureus isolates.
- Identify and explore novel therapeutic targets.
The methodologies used will include molecular microbiology, ‘omic analysis, human tissue culture and advanced imaging microscopy techniques. The team includes microbiologists, clinicians, and government agencies e.g UKHSA and Professor Joan Geoghegan, University of Birmingham. This is an exciting, inter-disciplinary project with environment and healthcare implications and opportunities.
Techniques that will be undertaken during the project
Microbiological and biochemical techniques, RNA, DNA, protein, metabolomic analysis, bioinformatics, tissue culture, electron and fluorescence microscopy,
Enquiries
Project Enquiries to [contact details available in the full listing]
Programme enquiries to [contact details available in the full listing]
To apply please refer to
https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp
Funding Notes
All MIBTP students will be provided with a 4 year studentship. This includes: Tuition fees at the UK fee rate*, a tax free stipend which for 2026/7 is £21,805 per year (2027/8 stipend to be confirmed), a travel allowance over years 1-3, a travel/conference budget, a generous consumables budget, use of a laptop for the duration of the programme. The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.
References
Environ Microbiol. 20:[contact details available in the full listing]; MBio. 2018 9. pii: e00550-18; BIORXIV-[contact details available in the full listing]v1-Morrissey
