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  Investigating how large-scale genome instability in fungi contributes to the host-pathogen interactions.


   School of Biosciences

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  Dr Hung-Ji Tsai  Applications accepted all year round  Competition Funded PhD Project (Students Worldwide)

About the Project

Fungal infections affect billions of people, including >1.5 million global deaths each year. Our failure to achieve cure against fungal infections results from the high levels of tolerance and resistance to antifungal drugs in clinical fungal isolates. While there are only three antifungals in the clinics, the rapid emergence of multi-drug resistant fungal pathogens is devastating. In 2019, CDC, for the first time, listed two fungal pathogens (Candida albicans and Candida auris) as serious/urgent threats in antimicrobial resistance. Despite the clinical importance, our understanding of underlying mechanisms in the development of antifungal resistance remains little, and to date, there is no direct clinical strategy to combat drug resistance.

One common challenge targeting antifungal resistance is the causal relationship between large-scale genome instability (e.g., aneuploidy) and the evolution of drug resistance. While “aneuploidy” is a collective term of thousands of random chromosome stoichiometries, the indefinite genome types confer a wide range of phenotype variation and have prevented the development of strategies against aneuploid diseases. However, whether and how these genome aneuploidization events occur remains elusive, especially at the host-pathogen axis. This project aims to investigate the evolution of antifungal resistance and to identify novel host and fungal factors contributing to this adaptive process.  

Biological Sciences (4)

References

Tsai, HJ., Nelliat, A.R., Choudhury, M.I. et al. Hypo-osmotic-like stress underlies general cellular defects of aneuploidy. Nature 570, 117–121 (2019). https://doi.org/10.1038/s41586-019-1187-2
Tsai, H.-J.; Nelliat, A. A Double-Edged Sword: Aneuploidy is a Prevalent Strategy in Fungal Adaptation. Genes 2019, 10, 787. https://doi.org/10.3390/genes10100787

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