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  (BBSRC DTP) Live imaging of translation dynamics in the Drosophila embryo


   Faculty of Biology, Medicine and Health

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  Prof Hilary Ashe, Prof M Rattray, Prof Mark Ashe  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

Recent technological advances that have allowed transcription to be visualised live in cells are revolutionising our understanding of mRNA production dynamics. However, it is also clear that mRNAs have very different rates of translation such that the level of a mRNA does not necessarily correlate with the amount of the encoded protein that accumulates in the cell. Therefore, the aim of this project is to determine mRNA translation dynamics in the early Drosophila embryo. This project will analyse existing ribosome profiling data, which gives a measure of the translatability of every mRNA expressed in the early embryo, to identify mRNAs with either very high or low translation rates. Translation of these mRNAs will then be visualised live in the Drosophila embryo to validate the translation dynamics, by combining CRISPR genome engineering with cutting edge imaging techniques. mRNA sequences underpinning these dynamics will be identified and mutated to determine the resulting effects on cell fate decisions during embryonic development. Overall, results from this project will serve as a paradigm for understanding how mRNA translation dynamics control development and become disrupted in disease situations.

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

Deignan, L., Pinheiro, M., Sutcliffe, C., Saunders, A., Wilcockson, S., Zeef, L., Donaldson, I. and Ashe, H.L. (2016). Regulation of the Dpp signaling-responsive transcriptional network in the Drosophila embryo. PLOS Genetics 12, e1006164.
Honkela, A., Peltonen, J., Topa, H., Charapitsa, I., Matarese, F., Grote, K., Stunnenberg, H.G., Reid, G., Lawrence, N.D. and Rattray, M. (2015). Genome-wide modeling of transcription kinetics reveals patterns of RNA production delays. Proceedings of the National Academy of Sciences, 112(42), pp.13115-13120.

Costello, J., Castelli, L.M., Rowe, W., Kershaw, C.J., Talavera, D., Mohammad-Qureshi, S.S., Sims, P.F., Grant, C.M., Pavitt, G.D., Hubbard, S.J. and Ashe MP. (2015). Global mRNA selection mechanisms for translation initiation. Genome Biol. 5;16:10.

Newton, F., Harris, R., Sutcliffe, C. and Ashe, H.L. (2015). Coordinate post-transcriptional repression of Dpp-dependent transcription factors attenuates signal range during development. Development, 142, 3362-73.

Saunders, A., Core, L.J., Sutcliffe, C., Lis, J.T. and Ashe, H.L. (2013). Extensive Polymerase pausing during Drosophila axes patterning enables high-level and pliable transcription. Genes & Development 27, 1146-58.