MSc By Research: Research project Exploiting fungal cell wall remodelling mechanisms to combat antifungal drug tolerance


   School of Medicine, Medical Sciences & Nutrition

  , , , Dr Louise Walker  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The MSc by Research programme at the University of Aberdeen is for students interested in a research-intensive master's degree. It is designed specifically to enhance your skills for a PhD or research career. If you have your own ideas for a research project in this area, we would love to hear from you! Please reach out to one of the project supervisors above to discuss your ideas.

You can find further information about our academic requirements and programme structure here.

prevalent in the clinic due to the high frequency of antifungal drug resistance seen with these species. Currently there are only three main classes of antifungal drug available in the clinic and resistance to two of these main classes is very common in these species. Fungi can alter the composition and architectures of their cell walls in response to environmental stimuli including exposure to antifungal drugs. In turn these alterations in the cell wall have been shown to reduce the susceptibility of the fungus to echinocandin class of antifungal drug. Recently it has become apparent that the outer glycoshield, the mannan layer of the cell wall becomes thickened in antifungal tolerant and resistant clinical isolates of Candida glabrata and Candida parapsilosis affecting susceptibility to both echinocandin and azole drugs. This mannan layer is formed from heavily glycosylated cell wall proteins.

 In this project we will dissect the mechanisms that result in thickening and upregulation of the outer mannan layer in these important pathogens. We will test if exposure to other stresses, commonly encountered in the human host also results in mannan upregulation. We will then use readily available signalling and glycosylation mutants as well as chemical inhibitors to identify the genes and pathways that coordinate stress-induced alterations in cell wall glycosylation.

The main objectives are therefore to (1) identify which environmental signals alter the outer mannan layer of Candida glabrata and Candida parapsilosis, (2) gain an understanding of the molecular mechanisms that control mannan production and the downstream enzymes that coordinate mannan synthesis, (3) examine how altered mannan production influences drug susceptibility and host interactions.

This project will provide training in fungal cultures, drug susceptibility testing, cell wall analysis using biochemical, flow cytometry and fluorescent microscopy with image and data analysis. Other skills will include host interaction assays, e.g. challenge with immune cells such as primary human neutrophils and PBMCs. 

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Applicants to this project should hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant subject.

We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.

Informal enquiries are encouraged, please contact Professor Carol Munro () for further information.

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APPLICATION PROCEDURE:

Please note: This is a self-funded opportunity.

  • Prospective students should contact the lead supervisor (via the email address listed above) to discuss the research project and complete a proposal form prior to / or shortly after applying.
  • Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
  • You should apply for Medical Sciences (MSc) to ensure your application is passed to the correct team.
  • Please clearly note the name of the supervisor and the project title on the application form. If this is not included, your application may not be considered for the project.
  • Candidates should have (or expect to achieve) a minimum of a 2:1 UK Honours degree (or international equivalent) at undergraduate level.
  • Your application must include: a personal statement, an up-to-date copy of your academic CV, and clear copies of your educational certificates and transcripts.
  • If you are still undertaking your undergraduate degree, it is helpful to the selection panel if you could provide documentation showing your grades to date (this can be a screenshot from an online portal).
  • Please note: Project supervisors will not respond to requests for funding assistance.
  • If you require any additional assistance in submitting your application or have any queries about the application process, please don't hesitate to contact us at 
Biological Sciences (4) Medicine (26)

Funding Notes

This is a self-funding project open to students worldwide. Our typical start dates for this programme are February or October.
Fees for this programme are £4,712 for home/UK students, and £24,860 for international students.
Additional research costs / Bench fees of £3,000 will also apply.
The Scottish Government offers postgraduate loans to those due to start a Masters (taught or research) programme.

References

1) Buda De Cesare, G., Hafez, A., Stead, D., Llorens, C., Munro, C. A. (2022) Biomarkers of caspofungin resistance in Candida albicans isolates: a proteomic approach. Virulence 13:1, 1005-1018, DOI: 10.1080/21505594.2022.2081291
2) Ibe, C. and Munro, C.A. (2021) Fungal cell wall: An underexploited target for antifungal therapies. PLoS Pathog 17(4):e1009470. doi: 10.1371/journal.ppat.1009470.
3) Walker, L.A. and Munro, C.A. (2020) Caspofungin induced cell wall changes of Candida species influences macrophage interactions. Frontiers in Cellular and Infection Microbiology 10 doi: 10.3389/fcimb.2020.00164

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