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Understanding the commensal-to-pathogen transition – environmental cues and signalling cascades


   School of Cellular and Molecular Medicine

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  Dr Stephanie Diezmann  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Summary:

The yeast Candida albicans is a common commensal of the human gastrointestinal tract. Using a combination of microbiology, molecular biology, protein biochemistry and proteomics methods, this project aims to define the role of a Hsp90 phospho-switch 

Project description:

Heat shock protein (Hsp90) is a key regulator of fungal virulence (O’Meara et al., 2017). We previously identified and characterised the first Hsp90 phospho-switch, whose phosphorylation blocks Hsp90 function and consequently expressions of fungal virulence traits (Alaalm et al., 2021). This project aims to further define the role of this phospho-switch in the transition from harmless commensal to life-threatening pathogen in two evolutionarily divergent fungi. C. albicans, a human commensal and opportunistic pathogen and the plant pathogenic filamentous fungus Ashbya gossypii, which causes disease in cotton and is being vectored by insects (Wendland and Walther, 2005). The first aim is to identify which environmental cues result in phosphorylation in C. albicans and how phosphorylation affects downstream signalling cascades. The second aim is to determine if the residue is functionally conserved in A. gossypii


References

References:
Alaalm L, Crunden JL, Butcher M, Obst U, Whealy R, Williamson CE, O’Brien HE, Schaffitzel C, Ramage G, Spencer J, Diezmann S. 2021. Identification and phenotypic characterization of Hsp90 phosphorylation sites that modulate virulence traits in the major human fungal pathogen Candida albicans. Front Cell Infect Microbiol 11:1–14. doi:10.3389/fcimb.2021.637836
O’Meara TR, Robbins N, Cowen LE. 2017. The Hsp90 chaperone network modulates Candida virulence traits. Trends Microbiol 25:809–819. doi:10.1016/j.tim.2017.05.003
Wendland J, Walther A. 2005. Ashbya gossypii: A model for fungal developmental biology. Nat Rev Microbiol 3:421–429. doi:10.1038/nrmicro1148
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