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The molecular basis of a genetic susceptibility gene in Alzheimer’s disease: the case of cystatin C

Project Description

Degenerative diseases associated with ageing occur sporadically and are associated with the misfolding and aggregation of a number of proteins in vivo. Whereas aggregation can be triggered in vitro by the addition of denaturants, the heterogeneity of the structure of these aggregates and their dependence on environmental conditions begs the question as to how well such models can be representative of what occurs in the cell. In this respect, there is increasing evidence from the fields of genetics and cell biology that different amyloid forming proteins regulate each other’s toxicity. I propose that the candidate investigates the postulated interaction of cystatin C with amyloid beta peptide as an example of such a process. How does cystatin C carry out its protective function with regards to shielding cells from the toxicity of amyloid beta? The successful candidate will be trained in a very broad range of skills including the expression and purification of recombinant proteins from bacteria, biophysical techniques ( hplc, analytical ultracentrifugation, fluorescence and circular dichroism spectroscopies), electron microscopy and atomic force microscopy (for the observation of fibrillar and non-fibrillar forms of amyloid aggregates and derivatives) and multi-dimensional NMR (for the structural mapping of complexes using both direct and indirect labelling techniques).

Science Graduate School

As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School – a community of postgraduate researchers working across biology, chemistry, physics, mathematics and psychology. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience technologies that are used in academia, industry and many related careers. Visit to learn more.

Funding Notes

Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD position, you must complete the University's application form using the following link: View Website

*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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