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The role of fungal membrane organization in directional growth and tissue invasion by Candida albicans. MRC Centre for Medical Mycology – PhD (Funded)

Project Description

Academic Supervisors:

Dr Alex Brand, University of Exeter (email: )
Professor Peter Petrov, University of Exeter

Project Description:

Candida albicans is a commensal fungus in the human GI tract but it also causes infections ranging from the mucosal condition known as ‘thrush’, to life-threatening bloodstream infections that kill around 50,000 people a year. A key virulence trait of this fungus is the formation of penetrative filaments called hyphae, which invade host tissue to cause inflammation, sepsis and organ failure. Hyphae, like neurons, grow only at the tip and this requires the spatial organisation of protein complexes that are responsible for delivering new cell wall and membrane material towards the tip. Our previous work suggests that different membrane domains play an important role in localising proteins that regulate polarised tip growth. The primary aim of this project is to find out how these membrane domains are spatially generated and how they interact with regulatory proteins to control invasive growth behaviour. The first stage will be to mutate cell polarity proteins with membrane-binding domains and observe their localisation within the cell using GFP tagging. Next, we will examine how the membrane domains are formed by kinases and flippases and use live-cell imaging to determine the effect of disrupting these on cell polarity organisation. These approaches will use molecular tools to generate strains that will be characterised using a variety of biophysical approaches, with cross-disciplinary expertise from the field of membrane dynamics. Lastly, we will test the mutants for their ability to penetrate host cell layers and escape from immune cells. The project will be carried out within the state-of-the-art laboratories of the MRC Centre for Medical Mycology in the Biosciences building at Exeter, which adjoins the Living Systems Institute and the Physics building. The skills learned will equip the student to pursue careers in any cell biology or biophysics-related field from growth and development to disease and drug discovery. The new understanding this project will generate may suggest strategies to disrupt domain organisation in pathogenic fungi and offer new antifungal treatments for invasive disease.

This award provides annual funding to cover UK/EU tuition fees and a tax-free stipend. For students who pay UK/EU tuition fees the award will cover the tuition fees in full, plus at least £15,009 per year tax-free stipend. Students who pay international tuition fees are eligible to apply, but should note that the award will only provide payment for part of the international tuition fee and no stipend.

The studentship will be awarded on the basis of merit for 3.5 years of full-time study to commence in November 2019.

Funding Notes

The University of Exeter’s College of Life and Environmental Sciences is inviting applications for a fully-funded PhD studentship to commence in November 2019 or as soon as possible thereafter. For eligible students the studentship will cover UK/EU tuition fees plus an annual tax-free stipend of at least £15,009 for 3.5 years full-time, or pro rata for part-time study. The student will be based in the MRC Centre for Medical Mycology, Biosciences, in the College of Life and Environmental Sciences at the Streatham Campus in Exeter.

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