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The fundamental requirements and components of translation factories for the co-ordinated production of key proteins and pathways in yeast


   Faculty of Biology, Medicine and Health

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

About the Project

Understanding the mechanisms surrounding the coordinated production of protein in biotechnological organisms such as baker’s yeast (S. cerevisiae) is important in many biotechnological applications. S. cerevisiae has been used in fermentations for centuries and has become a workhorse of the biotechnology industry. It has been used for the production of industrially important enzymes, various pharmaceuticals (including proinsulin, a-interferon, prochomysin and b-endorphins), and vaccines such as those targeting human papillomaviruses. All of these applications rely upon the engineered overproduction of specific proteins or groups of proteins.

Recently, we have shown that certain ubiquitously expressed and heavily translated mRNAs are localised to specific translation factories. We have defined new classes of RNA granule termed CoFe (Core Fermentation) granules that contain the majority of the glycolytic mRNAs and Translation Factor (TF) granules that contain many translation factor mRNAs. We postulate that the CoFe and TF granules play roles in highly efficient and co-ordinated translation, allowing cells to manage and harmonize the production of components from the same protein complex and/or metabolic pathway. As such, these granules represent intracellular factories for the production of related proteins. In this project, a student will seek to define a set of rules dictating the maintenance and composition of these factories. Using this information, they will address the functional importance of the factories and potential applications of this knowledge to the production of biotechnologically relevant proteins in yeast.

Entry Requirements

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 previous life science undergraduate/master’s degree in disciplines such as biochemistry, cell biology or genetics are particularly encouraged to apply. 

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

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.

Incomplete applications will not be considered and withdrawn.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website View Website

References

Morales-Polanco F, Bates C, Lui J, Casson J, Solari CA, Pizzinga M, Forte G, Griffin C, Garner KEL, Burt HE, Dixon HL, Hubbard SJ, Portela P, Ashe MP. 2021. Core Fermentation (CoFe) granules focus coordinated glycolytic mRNA localization and translation to fuel glucose fermentation. iScience. 24: 102069. doi: 10.1016/j.isci.2021.102069.
Kershaw CJ, Nelson MG, Lui J, Bates CP, Jennings MD, Hubbard SJ, Ashe MP, Grant CM. 2021. Integrated multi-omics reveals common properties underlying stress granule and P-body formation. RNA Biol. 18:655-673. doi: 10.1080/15476286.2021.1976986. PMID: 34672913
Pizzinga M, Bates C, Lui J, Forte G, Morales-Polanco F, Linney E, Knotkova B, Wilson B, Solari CA, Berchowitz LE, Portela P, Ashe MP. 2019. Translation factor mRNA granules direct protein synthetic capacity to regions of polarized growth.
J Cell Biol. 218:1564-1581. doi: 10.1083/jcb.201704019.
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: 944-54. doi: 10.1016/j.celrep.2014.09.040.

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