Understanding the interaction and functional mechanism of mitochondrial MIA pathway

Mitochondria are vitally important organelles of living cells, which generate the primary energy for all biological activities. Mitochondrial dysfunction leads to life threatening diseases, such as cancer, diabetes, stroke, and various neurodegenerative diseases (e.g. Alzheimer’s and Parkinson’s diseases). About 99% of the mitochondrial proteins are synthesized in the cytosol, thus biogenesis and function of mitochondria stickily depend on import and folding of mitochondrial proteins. To this end, the mitochondrial import and assemble (MIA) pathway is used by most of mitochondrial intermembrane space proteins. The MIA pathway couples the protein import and oxidative protein folding together. The key components of MIA pathway included: a sulfhydryl oxidoreductase Mia40, disulphide bond generator Erv1 (called ALR in human), and cytochrome c of the respiration chain. Whilst the interactions between Mia40 and Erv1/ALR have been well studied, little is known about how Erv1 interacts with cytochrome c and the reaction is regulated. The overall aim of this project is to understand the molecular mechanism of Erv1/ALR-cytochrome c interaction, using both computer modelling and experimental approaches. Protein docking modelling will be used to map protein-protein interaction surface and identify key residues involved in yeast Erv1-cytochrome c and human ALR-cytochrome c. To test the models established from the computer modelling experimentally, the key residual mutation will be made, the proteins will be purified from E Coli., and characterised using biochemical and biophysical methods. This project will provide an excellent opportunity for a self-motivated student to learn and develop many essential bioinformatics and experimental skills in protein studies.

Entry Requirements

Candidates are expected to hold (or about to obtain) a minimum second class (for MPhil study) and upper second class (for PhD study) honours degree (or equivalent) in biochemistry, cell biology or a related subject. Candidates with experience in protein folding, characterisation, and/or computer modelling, with an interest in protein folding and protein biotechnology are 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/”