The fundamental requirements and components of translation factories for the biotechnological production of key proteins in yeast

Details

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.

Eligibility 

Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in a related area/subject. A life science undergraduate/master’s degree in disciplines such as biochemistry, cell biology or genetics.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Biotechnology Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

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: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/

References

Crawford RA, Eastham M, Pool MR, Ashe MP. 2024. Orchestrated centers for the production of proteins or “translation factories”. Wiley Interdiscip Rev RNA. 15: e1867. PMID: 39048533

Kershaw CJ, Nelson MG, Castelli LM, Jennings MD, Lui J, Talavera D, Grant CM, Pavitt GD, Hubbard SJ, Ashe MP. 2023. Translation factor and RNA binding protein mRNA interactomes support broader RNA regulons for posttranscriptional control. J Biol Chem. 299: 105195. PMID: 37633333

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. PMID 33554071

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. 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. 30877141