Currently, there are no known therapies to counter amyloid-related diseases such as Parkinson’s and Alzheimer’s. In an endeavour to understand the ways in which protein monomers self-assemble into the amyloid fibrils associated with these diseases, we have mapped the self-aggregation pathways of a range of amyloidogenic proteins using ion mobility-mass spectrometry. We have also established an efficient mass spectrometric assay to screen for small molecule inhibitors of self-assembly.
We aim to decipher the mechanism of amyloid protein ((amylin, A-beta, alpha-synuclein, beta-2-microglobulin) self-assembly and inhibition at the molecular level by elucidating interactions between such proteins and their assembly inhibitors, and also with in vivo factors including lipids.
We propose to (i) pin-point binding sites and conformational changes taking place when these proteins bind both inhibitors and in vivo factors using chemical labelling techniques; (ii) study the effect on the assembly pathways and intermediates in the presence of in vivo factors.
Following chemical labelling, the labelled sites will be mapped using tandem mass spectrometry coupled to liquid chromatography and/or ion mobility spectrometry.
The novelty of this project lies in developing and applying new methods and technologies to map protein self-aggregation, inhibition and cellular interactions in vitro at an unprecedented molecular level. This will be of importance not only in academia but also more widely in the medical and biopharmaceutical fields.
The research is intended to provide the student with experience in a broad base of biophysical and analytical skills to equip this person for a rewarding scientific career.
For further information see the web-sites: http://www.astbury.leeds.ac.uk or
or contact: [email protected]
Applications are welcomed from students with biological, chemical or physical science backgrounds.
More details about research in our research groups can be found at:
Please contact [email protected]
for more information.