About the Project
We will build upon our recent analysis of structures determined for complexes formed between the translation factors eIF2 and eIF2B . We have biochemical evidence for multiple modes of interaction between eIF2, eIF5 and eIF2B and aim to define these further. Biochemical and biophysical techniques (such as chemical cross-linking and small angle X-ray scattering (SAXS)) will also be used to monitor the assembly of a various complexes to aid trapping transient complexes for structural analysis. These experiments will allow deeper understanding and provide insight into the structures and functions of these factors, guide future functional experimentation and provide insight into human disorders.
The factor eIF2 is phosphorylated in response to cellular stress and inactivates eIF2B by forming a stable complex--called the integrated stress response. Viruses such as coronavirus and picornavirus have evolved a mechanism to counteract this inactivation by producing a protein that binds to eIF2B and activates it, even in the presence of phosphorylated eIF2. We aim to find out more about these stress-response evading mechanisms.
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).
If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.
Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website http://www.manchester.ac.uk/bbsrcdtpstudentships
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 View Website
2. Jennings MD, Kershaw CJ, Adomavicius T and Pavitt GD* (2017). Fail-safe control of translation initiation by dissociation of eIF2α phosphorylated ternary complexes. eLife doi: 10.7554/eLife.24542
3. Adomavicius T, Guaita M, Zhou Y, Jennings MD, Latif Z, Roseman AM*, Pavitt GD* (2019) The structural basis of translational control by eIF2 phosphorylation. Nature communications 10, 2136. doi: 10.1038/s41467-019-10167-3
4. Rabouw, H.H., Visser, L.J., Passchier, T.C. et al. Inhibition of the integrated stress response by viral proteins that block p-eIF2–eIF2B association. Nat Microbiol (2020).
Why not add a message here
Based on your current searches we recommend the following search filters.
Based on your current search criteria we thought you might be interested in these.
Investigating the time course of vitamin D storage in human adipose and skeletal muscle and the relationship to skeletal muscle protein synthesis, (BBSRC SWBio DTP funded) PhD studentship
University of Exeter