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Metals and infectious disease: Characterising metal handling systems in bacterial pathogens

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  • Full or part time
    Dr Cavet
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Bacterial infectious diseases remain a leading cause of death worldwide. Metals (such as iron, zinc, copper and manganese) play a central role in the outcome of bacteria-host interactions. To control infections, in a process termed nutritional immunity, the immune system exploits both the need for bacteria to acquire metals in order to proliferate and the innate toxicity of metal ions. In response, pathogenic bacteria have evolved a myriad of metal-sensing, metal-acquisition and metal-detoxification systems which represent key virulence determinants. These systems offer attractive targets for the development of much needed novel antimicrobial agents as well as opportunities to exploit nutritional immunity. Our laboratory is uncovering and characterising these systems, and examining their roles in allowing bacterial pathogens to adapt to metal stresses within the host environment. The current focus organisms are the food-borne pathogens Salmonella and Listeria. PhD projects are available to characterise novel metal sensing and metal homeostatic proteins from these organisms and examine their contributions to virulence. The student will join the Molecular Microbiology Group based in the Michael Smith Building at the University of Manchester with state of the art facilities, and will receive a broad training in molecular biology, protein biochemistry, cell biology and microbiology (techniques will include DNA and RNA manipulation, protein expression and purification, bacterial and mammalian cell culture, infection experiments). This training will provide an excellent basis for a career in biosciences research.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.

References

• Jesse HE, Roberts IS & Cavet JS (2014). Metal ion homeostasis in Listeria monocytogenes and importance in host-pathogen interactions. Advances in Microbial Physiology, 65: 83-123.
• Osman D, Patterson CJ, Bailey K, Fisher K, Robinson NJ, Rigby SE & Cavet JS (2013). The copper supply pathway to a Salmonella Cu,Zn-superoxide dismutase (SodCII) involves P1B-type ATPase copper efflux and periplasmic CueP. Molecular Microbiology 87:466-77.
• Corbett D, Wang J, Schuler S, Lopez-Castejon G, Glenn S, Brough D, Andrew PW, Cavet JS, & Roberts IS (2012). Two zinc uptake systems contribute to the full virulence of Listeria monocytogenes during growth in vitro and in vivo. Infection & Immunity 80: 14-21.
• Osman, D & Cavet, JS (2011) Metal Sensing in Salmonella: Implications for Pathogenesis. Advances in Microbial Physiology, 58, 175-232.
• Osman, D, Waldron, KJ, Denton, H, Taylor, CM, Grant, AJ, Mastroeni, P, Robinson, NJ & Cavet, JS (2010). Copper homeostasis in salmonella is atypical and copper-CueP is a major periplasmic metal complex. Journal of Biological Chemistry, 285: 25259-25268.

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