Prof Mark Ashe, Prof N Read, Prof Simon Hubbard
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
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.
http://www.manchester.ac.uk/research/mark.p.ashe/research
http://www.manchester.ac.uk/research/simon.hubbard/research
http://www.manchester.ac.uk/research/nick.read/research
Funding Notes
This project is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
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.