In the middle of applying to universities? | SHARE YOUR EXPERIENCE In the middle of applying to universities? | SHARE YOUR EXPERIENCE

Regulatory roles for ribosome-associated proteins in protein synthesis


   Faculty of Biology, Medicine and Health

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

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 proteins and GTP-binding “G proteins”. G proteins commonly act as molecular switches to regulate a wide-range of cellular events. Although 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. Similarly there are many RNA-binding proteins that modulate the translatability of bound mRNAs.

In parallel with other ongoing studies, this project will make use of modern molecular genetic tools to study how one or 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.

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 laboratory experience are particularly encouraged to apply.

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.

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 2 fee. Details of our different fee bands can be found on our website View Website

References

1. Merrick WC, Pavitt GD (2018) Protein Synthesis Initiation in Eukaryotic Cells.
Cold Spring Harb Perspect Biol. 10(12):a033092. doi: 10.1101/cshperspect.a033092.
2. Crawford RA, Pavitt GD. (2019) Translational regulation in response to stress in Saccharomyces cerevisiae. Yeast. 36(1):5-21. doi: 10.1002/yea.3349.
3. Jadhav B, Wild K, Pool MR, Sinning I. (2015) Structure and Switch Cycle of SRβ as Ancestral Eukaryotic GTPase Associated with Secretory Membranes. Structure. 23:1838-47.
4. Adomavicius T, Guaita M, Zhou Y, Jennings MD, Latif Z, Roseman AM, Pavitt GD. (2019). The structural basis of translational control by eIF2 phosphorylation.
Nat Commun. 10(1):2136. doi: 10.1038/s41467-019-10167-3.
5. Crawford RA, Ashe MP, Hubbard SJ, Pavitt GD (2022) Cytosolic aspartate aminotransferase moonlights as a ribosome binding modulator of Gcn2 activity during oxidative stress.
eLife. 2022 May 27;11:e73466. doi: 10.7554/eLife.73466

Email Now


Search Suggestions
Search suggestions

Based on your current searches we recommend the following search filters.

PhD saved successfully
View saved PhDs