Investigating how ageing affects host-pathogen interactions in a C. elegans model of fungal infection.

About the Project

Fungal pathogens kill more people every year than malaria. Candida albicans is a major human fungal pathogen, causing over 400,000 deaths per annum. Invasive Candida infections have a mortality rate of between 40-60% exacerbated by the emergence of resistance to the limited number of anti-fungal drugs. Hence, there is an urgent need to understand how these ‘hidden killers’ overcome immune defences: Systemic fungal infections occur when opportunist fungal pathogens overcome host innate immune defences, making the elderly and immunocompromised particularly vulnerable. Innate immune defences include stress-responsive signalling pathways that are conserved in the nematode worm Caenorhabditis elegans. Their transparency, and ease of genetic manipulation and analysis make C. elegans an ideal, ethical model to investigate how these defences prevent infection.

Until now, the C. albicans traits that promote immune evasion and anti-fungal resistance have been studied using mixed populations of fungal cells of differing ages. However, the research team have established a novel ‘track and trace’ methodology that uses fluorescent labelling to separate young and old subpopulations of Candida cells within cultures of mixed age cells. Using this approach they have made the exciting discovery that ‘aged’ Candida cells tolerate higher levels of anti-fungal drugs. This project will test the hypothesis that drug resistant ‘aged’ fungal cells also bypass host innate immune defences.

This multidisciplinary project will utilise state of the art fluorescent activated cell sorting and fluorescent microscopic imaging in transgenic and immunocompromised mutant C. elegans.

Together the advantages of the C. elegans model of infection and the ‘track and trace’ system will combine to provide a unique opportunity to determine how drug-resistant sub populations of cells contribute to infection in an immunocompromised host. Identifying new host-Candida interaction mechanisms will aid development of new therapeutics to mitigate the growing problem of anti-fungal resistance. The placement with the industrial partner will provide a great opportunity to take the first steps to exploit these findings by identifying new approaches to upregulate innate immune defences to protect against systemic disease.

Based in Newcastle University Medical School you will be a valued member of a well equipped and supportive research team investigating how to target fungal pathogens and augment host stress responses that protect against ageing and disease. https://research.ncl.ac.uk/newcastlefungalgroup/

Both supervisors are committed to the training and career progression of early career researchers, including PhD students leading research publications https://www.ncl.ac.uk/medicalsciences/people/profile/elizabethveal.html https://www.ncl.ac.uk/dental/people/profile/alessandrada-silva-dantas1.html.

Candidates are strongly encouraged to contact Dr Veal informally (e.a.veal@ncl.ac.uk) for further project details.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.

HOW TO APPLY

Please complete the following application form – Google Form

Applicants can only apply for 1 project; any additional applications will not be accepted.

Applicants should send the following documents to FMSstudentships@newcastle.ac.uk:

• a CV (including contact details of at least two academic (or other relevant) referees).
• a Cover letter – stating your project choice, as well as including additional information you feel is pertinent to your application.
• copies of your relevant undergraduate degree transcripts and certificates.
• a copy of your IELTS or TOEFL English language certificate (where required)
• a copy of your passport (photo page).