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Functional and mechanistic analysis of mRNA localisation and its role in polarised growth for S. cerevisiae and the pathogenic fungus Aspergillus fumigatus.


Project Description

Life threatening fungal diseases annually kill more people than malaria, tuberculosis or breast cancer and Aspergillus fumigatus is the most important human pathogenic filamentous fungus. The highly polarized invasive hyphal growth and the nutritional versatility of A. fumigatus have been identified as key parameters contributing to its virulence.
Recent work from the Ashe lab in the budding yeast Saccharomyces cerevisiae suggests that mRNA localisation to granules in actively growing cells plays important roles for key pathways. More specifically, mRNAs encoding components involved in energy generation and protein synthesis are co-ordinately translated in novel granules that we have termed ‘translation granules’ (TGs). This co-ordinated production of proteins involved in energy generation and protein synthesis in TGs could play an important role in polarised growth during pseudohyphal growth in S. cerevisiae and in the much more rapid, hyphal tip growth of filamentous fungi such as A. fumigatus. In this project a student will expand work in S. cerevisiae into strains exhibiting pseudohyphal growth, then investigate the inheritance and dynamics of mRNA granules. Complementary to this, the student will establish a robust live cell system for monitoring the localisation dynamics of mRNAs in actively growing and branching A. fumigatus hyphae. They will then further delineate mechanistic and physiological questions using these two systems, in conjunction with bioinformatic and genetic approaches.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk.

Funding Notes

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in microbiology and an interest in fungal biology are encouraged to apply.

This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

Informal enquiries may be made directly to the primary supervisor.

References

Lui J, Castelli LM, Pizzinga M, Simpson CE, Hoyle NP, Bailey KL, Campbell SG, Ashe MP (2014) Granules harboring translationally active mRNAs provide a platform for P-Body formation following stress. Cell Rep. 9: 944.

Sfakianos AP, Whitmarsh AJ, Ashe MP (2016) Ribonucleoprotein bodies are phased in. Biochem Soc Trans. 44: 1411.

Lawless C, Holman SW, Brownridge P, Lanthaler K, Harman VM, Watkins R, Hammond DE, Miller RL, Sims PF, Grant CM, Eyers CE, Beynon RJ, Hubbard SJ (2016) Direct and Absolute Quantification of over 1800 Yeast Proteins via Selected Reaction Monitoring. Mol Cell Proteomics. 15: 1309.

Muñoz A, Bertuzzi M, Bettgenhaeuser J, Iakobachvili N, Bignell EM, Read ND. (2015). Different stress-induced calcium signatures are Reported by aequorin-mediated calcium measurements in living cells of Aspergillus fumigatus. PLoS One 10: e0138008.

Costello J, Castelli LM, Rowe W, Kershaw C, Talavera D, Mohammad-Qureshi S, Sims P, Grant CM, Pavitt G, Hubbard SJ, Ashe MP. (2015) Global mRNA selection mechanisms for translation initiation. Genome Biol. 2015 16:10.

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