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(BBSRC DTP) Mechanism of early steps in protein synthesis by cryoEM imaging of supramolecular complexes


Project Description

The aim of this project is to understand the mechanism and control of protein synthesis in eukaryotic cells at the molecular level, particularly focused around the role of the eukaryotic translation initiation factors eIF2, eIF5 and eIF2B. Protein synthesis is a multistep process that relies on a dynamic series of protein-protein and protein-RNA interactions necessary to assemble ribosomes, factors, tRNAs and mRNA. This project will use recombinant protein expression systems to purify specific protein complexes and then use electron microscopy techniques to determine their 3-dimensional structures. Analysis of the structures will provide insight into their critical role in protein synthesis and its control, and relevance to human health and disease. For example, mutations in eIF2B cause a genetically inherited brain disease, while regulation of eIF2B activity is critical for a wide variety of cues, including: nutritional responses, stress, fighting viral infections, and long-term memory.
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.

http://www.manchester.ac.uk/research/Alan.Roseman/
http://www.manchester.ac.uk/research/Grahan.Pavitt/
http://www.manchester.ac.uk/research/Clair.Baldock/

Entry Requirements:
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.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Partnership. 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 View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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