About the Project
Critically, sorting of EGFR to the degradative pathway is accompanied by acidification of the endosome/MVB, which promotes endosomal maturation and the exposure of EGFR to active lysosomal hydrolases. Based on recent published phosphoproteomics data, we believe that activated EGFR promotes endosome acidification by regulating a family of membrane proteins that couple the endosomal proton pump to membrane trafficking. We will test whether this is the case, as part of a broad examination of how signalling determines how EGFR negotiates the endocytic pathway. Specifically, Interferon induced transmembrane proteins (IFITMs) are tyrosine phosphorylated in response to EGF stimulation, raising the possibility that IFITMs are signalling targets that control the endosomal trafficking of EGFR.
In other contexts, IFITMs are essential for the acidification and maturation of endosomes carrying pathogenic bacteria, raising the possibility that regulation of IFITMs controls transit of EGFR through acidifying endocytic compartments, towards lysosomal degradation. This novel hypothesis merits further investigation. The overall objective of the PhD will be to establish how IFITMs couple endosomal acidification to other aspects of transport through endosomes towards the lysosome.
1. Verify how members of the IFITM family are phosphorylated downstream of EGFR.
2. Dissect the role of IFITMs in EGFR transit through the endocytic pathway.
Training/techniques to be provided:
The project will use a wide range of cell biology skills to manipulate protein function and to test effects on EGFR trafficking and cell fate. Techniques will include: cell culture, transfection, RNAi, CRISPR, fluorescence microscopy, biochemistry (e.g. immunoblotting, phospho-peptide analysis), mass spectrometry.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject.
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. For more information please visit http://www.internationalphd.manchester.ac.uk
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.
 Francavilla C et al. Nature Structural and Molecular Biology 23, 608-618, (2016).
 Woodman P and Tabernero L Biochem. Soc. Trans. 46, 1037-1046 (2018).
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