Protein Misfolding and the Molecular Basis of Alzheimer’s Disease
Note that this project is only offered to China Scholarship Council, CONACYT and Ciência sem Fronteiras funded students.
Please indicate how you intend to fund your PhD when contacting the School or supervisor.
Project Background: 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 earley stagies of the amyloid cascade are charictorised by the self-accossiation 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).
Aim: 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 expertize 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 the University of London has recently joined the Russell group and is one of leading research focused institutions in the UK. The successful applicant will enter a vibrant research environment, under the supervision of Dr John H Viles. Currently (2014) four PhD students and a Wellcome-Trust postdoc, who have considerable expertise between them. 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. With 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 Associated Professor in Biochemistry. For details see:
Applications are invited from candidates with, or expecting to be awarded, at least an upper-second class degree (or equivalent qualification) in an area of biochemical-sciences. International students are required to provide evidence of their proficiency in English language skills.
The applicant must obtain an external source of funding.
To apply: Please complete an online application form via the following link: http://www.sbcs.qmul.ac.uk/prospectivestudents/research/studentships
Financial support: Four years of financial support from the China Scholarship Council (CSC) (http://en.csc.edu.cn) to undertake PhD research at University of London, Queen Mary, studying Protein Misfolding and the Molecular Basis of Alzheimer’s Disease with Dr John H VilesApplication:
Part A) Submit a CV and application form to Queen Mary, University of London
If you are successful we will write a short research proposal together, and a conditional offer dependant of obtaining a CSC Funding award will be made.
Part B) You will also apply directly to the China Scholarship Council for financial support during your PhD using our conditional offer from Queen Mary, University of London to study with Dr John Viles
Eligibility: B.Sc. in Biochemistry (or similar) from a top university anywhere in the world (i.e. China, Mexico, Brazil, etc). You will also have evidence of excellent spoken and written English skills. Applications are invited from candidates with, or expecting to be awarded, at least an upper-second class degree (or equivalent qualification) in an area of biochemical-sciences.
How good is research at Queen Mary University of London in Chemistry?
FTE Category A staff submitted: 14.00
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