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Resistance isn’t futile: Dissecting adaptation and antimicrobial resistance in pathogenic fungi


Project Description

What will you investigate?

We have only four major classes of antifungals to treat life-threatening fungal infections, which even with treatment will claim over 1 million lives this year. To make matters worse, antimicrobial resistance is an emerging threat to the treatment of these diseases. In fact, the Centers for Disease Control have listed drug-resistant Candida species on their list of ‘Serious Threats’ to public health.

Several studies have identified the mechanisms by which antifungals are effective at killing fungi and how fungi become resistant to antifungals. Antifungal treatment is also known to induce significant changes in intracellular reactive oxygen species [Lee & Lee 2018], in fungal cell walls [Hopke 2016] and can have paradoxical effects on survival in mammalian infections for Candida albicans, a major fungal pathogen [Lee 2012]. However, other Candida species are becoming more prevalent in the clinic, especially in highly vulnerable patient populations.

What we do not know is how adaptation to different antifungals in emerging pathogenic fungi contributes to their fitness in vivo and their interactions with host immune cells, both of which are critical for determining infection outcomes. By improving our understanding of how these emerging pathogenic fungi balance antifungal adaptation with survival in host niches, we can highlight new mechanisms to target for future drug development. Therefore, the aim of this project is to characterise how emerging Candida species respond to antifungal treatment, develop antifungal resistance, and explore their fitness in mammalian hosts. Ultimately, this project will significantly improve our understanding of how emerging pathogens adapt to antimicrobials and complex host environmental niches to cause disease.

What training will you receive?
You will be trained to become a well-rounded scientist who is able to communicate with scientific and general audiences. You will learn transferable skills: microbiological techniques, cell wall and phenotypic analyses, cytometric approaches (both microscopy and flow cytometry), and modern molecular approaches. You will have opportunities for career development and leadership training and be encouraged to present at national and international scientific conferences. You will also become a member of the world-renowned Aberdeen Fungal Group and join a family of excellent and highly collaborative scientists.

What comes next?
Upon successfully completing this project, you will have gained highly transferable skills in the life sciences that will help you drive research in both academic and industrial career paths. In addition, your training in communication and problem-solving skills will be transferable and competitive across employment sectors.

APPLICATION PROCEDURE:
This project is advertised in relation to the research areas of MEDICAL SCIENCES. Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php. You should apply for Degree of Doctor of Philosophy in Medical Sciences, to ensure that your application is passed to the correct school for processing

Funding Notes

Full funding for 4 years is available to UK/EU candidates only. Overseas candidates can apply for this studentship but will have to find additional funding to cover the difference between overseas and home fees (approximately £15,680 per annum).

Candidates should have (or expect to achieve) a minimum of a 2.1 Honours degree in a relevant subject. Applicants with a minimum of a 2.2 Honours degree may be considered provided they have a Merit/Commendation/Distinction at Masters level.

References

Lee & Lee 2018. A novel mechanism of fluconazole: fungicidal activity through dose-dependent apoptotic responses in Candida albicans. Microbiology; 164:194–204.

Hopke A, et al. 2018. Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion. Trends Microbiol 26: 284–295.

Lee et al. 2012. Antimicrob Agents Chemother. 56(1):208-17.

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