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The role mRNA-specific translation during chronological aging

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  • Full or part time
    Prof C M Grant
    Prof M Ashe
    Prof S Hubbard
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Biological ageing can be thought of as a progressive decline in the ability of an organism to survive stress and disease. It is a complex process which is influenced by both genetic and environmental factors. Yeast cells have been increasingly used as a model of ageing and have significantly contributed to our understanding of numerous conserved ageing genes and signalling pathways.

Yeast cells can survive for prolonged periods of time in culture and have been used as a model of the chronological life span (CLS) of mammals, particularly for tissues composed of non-dividing populations. In the CLS model, populations of stationary phase cells are maintained in liquid and various physiological parameters, such as viability, replication ability and metabolism, measured over time. Studies using this model have identified many key conserved ageing factors that modulate ageing. Translational activity is maintained in quiescent stationary phase cells, albeit at a much reduced rate compared with proliferating cells. However, very little is known about how translation is maintained in aged cells compared with actively growing cells, and whether mRNA-specific translation influences longevity.

This project will use a multidisciplinary approach to define the role of translational regulation during ageing. The key question to be addressed in this project is whether mRNA specific translation influences ageing, and if so, can altering translational activity moderate longevity.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a Biological science. Candidates with experience in molecular biology and an interest in gene expression are encouraged to apply.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website (https://www.bmh.manchester.ac.uk/study/research/fees/). 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.

References

Kershaw, C. J., Costello, J., Castelli, L. M., Rowe, W., Talavera, D., Sims, P. F. G., Ashe, M. P., Hubbard, S. J., Pavitt, G. D. and Grant, C. M. (2015) The yeast La Related Protein Slf1p is a Key Activator of Translation During the Oxidative Stress Response. PLOS Genet. 11: e1004903.

Costello, J., Castelli, L. M., Rowe, W., Kershaw, C. J., Sims, P. F. G., Grant, C. M., Pavitt, G. D., Hubbard, S. J., and Ashe, M. P. (2015) Global mRNA selection mechanisms for translation initiation. Genome Biol. 16: 10.

Castelli, L.M., Talavera, D., Kershaw, C.J., Mohammad-Qureshi, S.S., Costello, J.L., Rowe, W., Sims, P.F., Grant, C.M., Hubbard, S.J., Ashe, M.P. and Pavitt G.D. (2015) The 4E-BP Caf20p mediates both eIF4E-dependent and independent repression of translation PLOS Genet. 11: e1005233.

Kershaw, C.J, Costello, J,L., Talavera, D., Rowe, W., Castelli, L.M., Sims, P.F., Grant, C.M., Ashe, M.P., Hubbard, S.J. and Pavitt, G.D. (2015) Integrated multi-omics analyses reveal the pleiotropic nature of the control of gene expression by Puf3p. Sci Rep. 5: 15518.

Lawless, C., Holman, S.W., Brownridge, P., Lanthaler, K., Harman, V.M., Watkins, R., Hammond, D.E., Miller, R.L., Sims, P.F., Grant, C.M., Eyers, C.E., Beynon, R.J., and Hubbard SJ (2016) Direct and Absolute Quantification of over 1800 Yeast Proteins via SRM. Mol Cell Proteomics. 15:1309-22



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