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Calcium dynamics and signaling in Candida albicans during pathogenesis and drug resistance. MRC Centre for Medical Mycology, Biosciences – PhD (Funded)


Project Description

Academic Supervisors:
Dr Alex Brand, University of Exeter (email: )
Dr Duncan Wilson, University of Exeter (email: )

Project Description:
Candida albicans is a commensal fungus in the human GI tract but it can also cause the irritating mucosal infection known as thrush and life-threatening bloodstream infections that can lead to sepsis and death. Calcium ions in C. albicans play a crucial role in intracellular signalling during the switch to invasive filamentous growth and in response to antifungal drugs. We have developed new calcium and pH reporters with which to image calcium dynamics during development and cellular-stress responses for the first time in this fungus. This project will use molecular and genetic tools, coupled with live-cell imaging, to address three key questions about the role of calcium flux during antifungal drug responses and host tissue invasion. First, we will find out how C. albicans controls calcium flux by expressing our new reporter protein in a panel of calcium channel, pump and exchanger gene deletion mutants. Secondly, we will determine which signalling pathways are activated by calcium by mutating regulator proteins and quantifying changes in the expression of response genes. Thirdly, we will determine which of these signalling pathways are activated during tissue invasion and interactions with immune cells, by imaging changes in intracellular calcium flux during these real-time processes. This novel and exciting project will provide the student with cutting-edge skills in CRISPR-Cas9 gene editing technology, molecular genetics, live-cell imaging and gene expression analysis to explain how calcium dynamics helps the fungus to meet the challenges it encounters within the host.The project will be carried out within the state-of-the-art laboratories of the MRC Centre for Medical Mycology and the Bio-Imaging Centre, with input from computational scientists from the adjoining Living Systems Institute at Exeter. The breadth of skills learned will equip the student to pursue careers in any cell biology-related field from growth and development to disease and drug discovery.

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. 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.

Funding Notes

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. 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.

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