The genetic and/or epigenetic nature of antifungal drug tolerance in Candida glabrata

OVERVIEW

To establish the molecular basis of antifungal drug tolerance in the human yeast pathogen Candida glabrata

Pathogenic fungi from the Candida genus are obligate human commensals, which cause disease when host immune systems are compromised. Treating such infections has become increasingly more challenging due to the rise in antifungal resistance. Recently it has been discovered that Candida species generate sub-populations of specialized antifungal tolerant cells when exposed to lethal concentrations of antifungal drugs. It is thought that this drug tolerant state provides an opportunity for cells to acquire the necessary genetic mutation to become antifungal resistant. Indeed, such drug tolerant cells are readily isolated from patients with recurrent Candida infections, underscoring their clinical relevance. However, very little is known about the establishment or maintenance of drug tolerance in Candida spp. Research suggests that drug tolerance is dictated by a unique transcriptional profile within tolerant cells, which is hypothesized to be epigenetically inherited.

This project aims to characterize the tolerant state in the clinically relevant pathogenic yeast, Candida glabrata, and determine whether it is determined by genetic and/or epigenetic mechanisms. This project will investigate the frequency, reproducibility and stability of the drug tolerant state under different antifungal drug regimes. This analysis will be undertaken in both wild-type (WT) C. glabrata as well as in genetically modified strains that lack key regulators of chromatin structure, such as histone acetyl-transferases and histone deacetylases. Next, state-of-the-art RNAseq and DNA sequencing technologies will be used to interrogate the transcriptome and genomes of WT drug tolerant cells respectively. In collaboration with the Wallace lab at the University of Edinburgh, we will analyse these datasets to identify molecular signatures of drug tolerance. Furthermore, taking a Systems Biology approach we will work with the Wallace lab to model our phenotypic and molecular data, to understand the biological variables that contribute to the stability of the drug tolerant state in C. glabrata.

Start Date: 1 October 2022

Duration: 3 years

How to apply: Applications must be submitted via https://dap.qub.ac.uk/portal/user/u_login.php

Skills/experience required:

UG degree in any of the following disciplines: Microbiology/Molecular Biology/Biomedical Science/Biochemistry

Computational/numerical literacy and eagerness to learn bioinformatics, Aseptic technique

Skills desired: Molecular biology laboratory skills, Bioinformatics or data analysis stills (Unix/R/Python)

Research Information

PhD Supervisors
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Career Prospects

Introduction
Queen’s postgraduates reap exceptional benefits. Unique initiatives, such as the DegreePlus/Future Ready Award, bolster our commitment to employability, while innovative leadership and executive programmes alongside sterling integration with business experts helps our students gain key leadership positions both nationally and internationally. Career prospects in the biological sciences are exceptionally good. To some extent it depends on the specific topic, of course, but laboratory-based and especially quantitative skills and the proven innovation of a PhD or MPhil are highly sought after. Degrees are very much in demand, both in commercial science and public sector research and development (e.g. drug discovery and development, crop and animal improvements and welfare, sustainable agriculture and resource use, human nutrition and health, animal health, ecological management, food safety and technology, scientific communications, regulation, and many more fields).

Employment after the Course
Graduates have gone on to be professional research scientists, consultants, or hold technical and junior executive positions in commerce and government.

ENTRANCE REQUIREMENTS

Graduate
The minimum academic requirement for admission to a research degree programme is normally an Upper Second Class Honours degree in a relevant subject from a UK or ROI HE provider, or an equivalent qualification acceptable to the University. Further information can be obtained by contacting the School.

International Students

For information on international qualification equivalents, please check the specific information for your country.

English Language Requirements

Evidence of an IELTS* score of 6.5, with not less than 5.5 in any component, or an equivalent qualification acceptable to the University is required (*taken within the last 2 years).

International students wishing to apply to Queen’s University Belfast (and for whom English is not their first language), must be able to demonstrate their proficiency in English in order to benefit fully from their course of study or research. Non-EEA nationals must also satisfy UK Visas and Immigration (UKVI) immigration requirements for English language for visa purposes.

For more information on English Language requirements for EEA and non-EEA nationals see: www.qub.ac.uk/EnglishLanguageReqs.

If you need to improve your English language skills before you enter this degree programme, INTO Queen’s University Belfast offers a range of English language courses. These intensive and flexible courses are designed to improve your English ability for admission to this degree.

HOW TO APPLY

Apply using our online Postgraduate Applications Portal and follow the step-by-step instructions on how to apply.

Find a supervisor

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To find a potential supervisor aligned with your area of interest, or if you are unsure of who to contact, look through the staff profiles linked here.

You might be asked to provide a short outline of your proposal to help us identify potential supervisors.