University of Sheffield - Department of Molecular Biology and Biotechnology / Department of Physics and Astronomy
|Salary:||£30,175 to £38,183 per annum, Grade 7|
|Contract Type:||Contract / Temporary|
|Placed on:||17th October 2016|
|Closes:||16th November 2016|
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Contract Type: Fixed-term for 36 months with a start date of 1 January 2017
Faculty: Faculty of Science
Location: Firth Court, Main Campus
Applications are invited for a BBSRC funded, 36 month fixed-term Research Associate position in the research groups of Dr Rosie Staniforth, Professor Jon Waltho, Professor Per Bullough (Molecular Biology and Biotechnology) and Professor Jamie Hobbs (Physics and Astronomy) to work on the multidisciplinary research project A Molecular Mechanism for a General Amyloid Re-Modelling Activity.
Our quality of life as we age is severely impaired by degenerative conditions which include Alzheimer's, Parkinson's and other notable diseases. The aggregation of different proteins into amyloids is responsible for this, but can also drive a number of other lesser known processes such as bacterial biofilm formation and HIV infectivity. Our proposal will address fundamental questions regarding how protein amyloid formation can be regulated, and hence make a step change in the ability of the scientific community to control this reaction and importantly, prevent toxic side reactions. Specifically, we will determine how an amyloid re-modelling agent binds to amyloids, what the molecular determinants of this apparent broad specificity are and how the re-modelling activity takes effect on the amyloid assemblies.
You will apply a combination of biophysical approaches to determine the molecular interactions between the amyloid re-modelling protein G3P and amyloid. Specifically, you will be responsible for implementing a novel competition-based hydrogen-exchange assay (in combination with NMR) to detect which parts of G3P bind amyloid fibrils. In addition, you will establish a molecular footprint for amyloids on G3P using mass spectrometry in combination with Photochemical Oxidation of Proteins (FPOP) technology. The large size of the effector G3P will enable direct visualisation of the complex with amyloids using the imaging technology that the University of Sheffield has recently invested in (in particular, cryo-EM). The relative orientations of molecules within the amyloid assemblies have the potential to reveal with near-atomic detail how the G3P grabs the amyloid for dismantling. This project will also develop novel fractionation techniques to reveal the different populations of oligomeric species populated during the time course for assembly and disassembly of fibrils.
You will work in close collaboration with a PhD student on the same research project, who will also handle the molecular modelling of the process.
You will hold a PhD (or equivalent experience) in a relevant life science discipline (biochemistry, biophysics or related), have extensive previous experience of protein chemistry and ideally experience in at least one of the following areas: amyloid (beta) fibrillisation reactions, NMR or electron microscopy.
Informal enquiries should be made to R.A.Staniforth@sheffield.ac.uk.
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