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Regulatory roles for ribosome-associated proteins in protein synthesis

Faculty of Biology, Medicine and Health

About the Project

Protein synthesis is a highly-conserved, dynamic and tightly controlled process that is central to the activity of all cells. All phases of translation can be controlled. Translational control by reversible modification of translation factors is one well-established mode of control. Another level of control that is less well understood is that ribosomes are not uniform or passive. Instead evidence is emerging that ribosomes play active roles in regulating both overall protein synthesis activity and that they can develop specialised roles regulating the translation of specific mRNAs. The code governing ‘specialised ribosomes’ is not yet clear, but to provide one example, in recent work we have uncovered that mRNA-binding LARP proteins are important for gene-specific translational control in response to oxidative stress (see reference 4 below). The LARP proteins are just some a large number of proteins known that interact with and potentially modify ribosome activities.

We are interested in two classes of ribosome-associated proteins RNA-binding protein and GTP-binding “G proteins”. This project would study one of a number of interesting proteins. G proteins commonly act as molecular switches to regulate a wide-range of cellular events. Some G proteins such as eIF2 and eEF1A have well defined roles in protein synthesis (see references 1 and 5 below). Other G protein roles are much less clear or are not known, despite the fact that protein homologs exist in all forms of life.

This project will make use of modern molecular genetic tools to study how one or more G protein interacts with ribosomes and functions to modulate protein synthesis. These studies will make use of the wide variety of molecular techniques available using a yeast-based cell system which contains factors with clear human homologs and highly conserved translation mechanism with all other eukaryotes.

Candidates are expected to have, or about to obtain, an upper second class (or equivalent) undergraduate degree in a related subject area. A Masters qualification in a similar area would be an advantage.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website). Informal enquiries may be made directly to the primary supervisor.


1. Dever TE, Goss-Kinzy T, Pavitt GD (2016) Mechanism and regulation of protein synthesis in Saccharomyces cerevisiae. Genetics 203:65-107
2. Castelli LM Talavera D, Mohammad-Qureshi SS, Kershaw CJ, Costello JL, Rowe W, Sims PF, Ashe MP, Grant CM, Hubbard SJ, and Pavitt GD (2015). The 4E-BP Caf20p mediates both eIF4E-dependent and independent repression of translation. PLOS Genetics 11:e1005233
3. Costello JL, Rowe W, Castelli LM, Kershaw CJ, Talavera D, Sims PF, Grant CM, Pavitt GD, Hubbard SJ and Ashe MP (2015) Global mRNA selection mechanisms for translation initiation. Genome Biology 16 (1), 10.
4. Kershaw CJ Costello JL, Castelli LM, Talavera D, Rowe W, Sims PF, Ashe MP, Hubbard SJ, Pavitt GD and Grant CM (2015) The yeast La Related Protein Slf1p is a Key Activator of Translation During the Oxidative Stress Response. PLOS Genetics 11(1):e1004903.
5. Jennings MD, Zhou Y, Mohammad-Qureshi SS, Bennett D, Pavitt GD (2013) eIF2B promotes eIF5 dissociation from eIF2•GDP to facilitate guanine nucleotide exchange for translation initiation. Genes Dev 27:2696-707

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