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(BBSRC DTP) Metals and bacterial virulence: overcoming metal intoxication during infection


Faculty of Biology, Medicine and Health

About the Project

Campylobacter jejuni is a globally important food-borne pathogen, being the leading bacterial cause of human acute gastroenteritis and responsible for an estimated 0.5 billion cases each year. This bacterium is able to colonize and persist in farm animals, particularly chickens, which are the major source of human campylobacteriosis. The public health significance of campylobacteriosis underlines the urgent need for new strategies to reduce infections, yet the mechanisms employed by C. jejuni to persist within the food chain and to colonise and infect its hosts are relatively poorly understood. Transition metals, such as zinc and copper, are known to play a central role in the outcome of bacteria-host interactions. To control infections the immune system exploits the need for bacteria to acquire these metals to proliferate, by restricting their availability in a process termed ‘nutritional immunity’, as well as the innate metal toxicity, by poisoning bacteria with antimicrobial concentrations. In response, pathogenic bacteria have evolved a myriad of metal-sensing, metal-acquisition and metal-detoxification systems that act to maintain metal homeostasis and represent key virulence determinants. This project will build on our previous work focussing on metals at the host-pathogen interface and will combine the expertise of three laboratories (Cavet – Metal handling in bacterial pathogens, Linton – Campylobacter biology and Lloyd – Metal reduction and metallic nanoparticle synthesis) in order to uncover and characterise the metal handling systems in C. jejuni. This will involve examining the factors associated with their regulation as well as examining their roles in allowing this pathogen to adapt to metal stress, including during the colonisation and infection of its animal and human hosts. In addition, with regard to the potential of metallic nanoparticles being exploited for their antimicrobial properties during food processing, the project will also seek to examine the roles of these metal handling systems in protecting against the antimicrobial activity of bacterially synthesised metallic nanoparticles. The initial focus will be on the characterisation of a recently identified C. jejuni virulence-associated operon that is linked to zinc and copper resistance. The project will involve a multidisciplinary approach that interfaces microbiology, infection biology, biochemistry, nanotechnology and chemistry. Proteins involved in handling metals represent attractive targets for the development of much needed novel antimicrobial agents and knowledge of how the metal homeostatic systems in C. jejuni contribute to survival within the food chain and its human and animal hosts will help inform future control strategies.


Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website http://www.manchester.ac.uk/bbsrcdtpstudentships

Funding Notes

Funding will cover UK tuition fees/stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website View Website

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