World-wide one in three people over the age of 65 will die with Alzheimer’s Disease (AD). The disease is characterised by deposits of amyloid plaques and fibrils of amyloid-beta peptide (Ab) are their main constituent. The early stages of the amyloid cascade are characterised by the self-association of Ab peptide into toxic oligomers and protofibrils, which then convert to mature amyloid fibers . Although the link between amyloid-beta peptide and Alzheimer’s disease is clear, the nature of the toxic form of Ab and the mechanism of toxicity is not well understood. The cellular prion protein and copper ions have been linked with AD-phenotype in animal models (Laurel et al Nature 2009, You et al PNAS 2012). We hypothesise that the cellular prion protein and copper ions can profoundly influence this protein misfolding pathway; trapping and promoting Ab in a toxic oligomeric form that disrupts synaptic function, (Viles, FASEB 2013, Viles, JBC 2010).
We want to further characterize the structure, interaction and nature of the prion protein and copper trapped oligomeric Ab complexes. In particular, we want to probe the toxicity and toxic mechanism of these trapped Ab oligomers at the synapse.
Methods and Training:
The PhD student will use and gain expertise in a range of biophysical and spectroscopic techniques (NMR, TEM, AFM, Florescence, IR, CD and EPR in the Viles lab) to probe the structure of the Ab/prion-protein and Cu/Ab complexes. The neurotoxic action of these isolated trapped oligomers will be studied using a range of approaches, including; (i) A vesicle model of membrane permeability (ii) Measurements of synaptic health (iii) Toxicity in Drosophila models (iv) Cell viability.
Environment and Support:
Queen Mary University of London is a member of the Russell group of leading UK universities and one of the UK’s leading research universities. The successful applicant will enter a vibrant research environment, under the supervision of Dr John H Viles. The lab is well equipped to carry out all the biophysical measurements outlined (> a million pounds of external funding in the past ten years) with world class TEM, AFM, NMR, and EPR facilities. Dr Viles has an outstanding track record in PhD student supervision - all past PhD student have submitted in four years and have generated high impact first author publications.
Dr John H. Viles is an Associate Professor in Biochemistry. For details see: https://www.qmul.ac.uk/sbcs/staff/johnviles.html
Applications are invited from candidates with, or expecting to be awarded, at least an upper-second class bachelors degree (or equivalent qualification) in biochemistry (or similar). International students are required to provide evidence of their proficiency in English language skills. Applicants from outside of the UK are required to provide evidence of their English language ability. Please see our entry requirements page for details: https://www.qmul.ac.uk/sbcs/postgraduate/phd-programmes/entry-requirements/
The applicant must obtain an external source of funding.
Please complete an online application form via the following link: https://www.qmul.ac.uk/sbcs/postgraduate/phd-programmes/application-process/
If your application is successful a conditional offer dependant of obtaining external funding will be made and Dr Viles will support you with in your application for funding.
This project is open to applicants intending to apply for external funding (e.g. China Scholarship Council, CONACYT, Commonwealth Scholarships). Please see our website for further details on Queen Mary's international funding partners: View Website
If you intend to apply for China Scholarship Council funding, the deadline to apply to Queen Mary is 31st January 2019.