This project will build on our recent exciting discovery that a novel chemical tool, the polymer styrene maleic acid (SMA), can ‘biopsy’ human vascular cells, extracting proteins from the membrane without killing the cells. This polymer inserts into lipid bilayers transiently before leaving as a ‘nanodisc’ containing a sample of the membrane (lipid and protein), maintaining structure and protein post-translational modifications. We have shown for the first time that this technique can obtain proteins without losing cell viability.
This project will explore SMA as a way to biopsy cells of the vasculature to obtain proteins and other biomarkers that inform disease diagnosis and/or management. Our targets will be the early markers of clinical atheroma in endothelial and smooth muscle cells, characterising the application in the identification of specific, key markers of a critically-important disease. This will be achieved using cells in culture, then extended to intact human vascular tissue. The techniques involved will include assays of cell viability and functional analyses, with protein characterisation by mass spectrometry and Western blotting. There is the possibility of further collaborative work to carry out analysis of model cells, to precisely establish the limits of detection for this novel cell biopsy technique.
The PhD will start when a suitable applicant is selected and funding confirmed. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) or above in a relevant subject. The funding is open to international students (subject to eligibility); self-funded students, or those with funding already available and seeking a suitable research project, are encouraged to apply. For further details, please contact Dr. Smith ([Email Address Removed]).
Lee SC, Knowles TJ, Postis VL, Jamshad M, Parslow RA, Lin YP, Goldman A, Sridhar P, Overduin M, Muench SP, Dafforn TR. A method for detergent-free isolation of membrane proteins in their local lipid environment. Nature Protocols 2016; 11(7):1149-62.
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