One of the biggest challenges for cells is responding to their ever-changing environment. Cells overcome stress by activating stress-responsive signalling pathways such as the ‘integrated stress response’ (ISR). The critical signalling event in the ISR is the phosphorylation of eukaryotic translation initiation factor, eIF2α, by one of four eIF2α kinases. eIF2 phosphorylation controls protein synthesis via inhibiting the activity of a partner complex, eIF2B.
eIF2B is a large protein complex composed of 5 subunits αβδγε, which are arranged as a dimer of pentamers. In cells, although eIF2B is a ubiquitously expressed protein complex, it displays specific cellular localisation patterns. This project builds on previous work from the group which has identified that these localisation patterns correspond to subcomplexes of eIF2B containing varied amounts of the 5 subunits. Further work has demonstrated that these subcomplexes show differential responses to the ISR.
While the ISR is critical for maintaining cell function, such responses can also play roles in establishing dysfunctional states associated with prolonged stress exposure and the development of diseases ranging from cancer to neurodegeneration. Therefore, understanding the functional relevance of these unique cellular distributions of eIF2B and the contribution of specific binding partners has the potential to understand why specific cells may respond to stress and disease differently.
This doctoral project will use a range of technologies to determine the specific composition of these eIF2B bodies. This project will allow the candidate to develop expertise in techniques including: cell biology; advanced confocal microscopy; LC-ESI-MS/MS and MALDI imaging. Training will be provided in relevant techniques.
This multidisciplinary PhD project will be based in the state-of-the-art laboratory facilities in the Biomolecular Sciences Research Centre, Sheffield Hallam University and will involve collaborative work with colleagues at the University of Manchester. The successful applicant will be joining a vibrant research team with established expertise in the area of translational control and MALDI imaging technology.
Eligibility
Information on entry requirements can be found at GTA Program Page
Applicants should have, or expect to achieve, a minimum 2:1 Honours degree (or equivalent) in an appropriate science-based degree. A Master’s degree in a relevant discipline would be an advantage as will be an interest in Cell biology, or Bioanalytical science. Suitable candidate should also be highly motivated with an interest in gene expression and translational control research.
How to apply
We strongly recommend you contact the lead academic, Dr Susan Campbell ([Email Address Removed]), to discuss your application.
Please visit our GTA program page for more information on the Graduate teaching assistant program and how to apply.
Start date for studentship: October 2021
Interviews are scheduled for: Mid July 2021
For information on how to apply please visit GTA program page
Your application should be emailed to [Email Address Removed] by the closing date of 30th June.