Protein Misfolding and the Molecular Basis of Alzheimer’s Disease
Supervisor: Dr John Viles
About the Project
Alzheimer’s disease has a profound impact on healthy ageing. It is characterized by the accumulation of a small neuro-toxic peptide, amyloid-beta (Aβ) which forms fibrous plaques within the brain. The early stages of the amyloid cascade involve the self-association of Aβ peptide into toxic oligomers and protofibrils, which then convert to mature amyloid fibrils. The mechanism by which Aβ is toxic to neurons is not well understood, however its ability to disrupt membrane integrity and cellular homeostasis is believed to be central to Alzheimer’s disease pathology. Aβ is reported to have various impacts on the lipid bilayer, including the formation of ion-channels and Aβ – lipid membrane interactions are thought to be fundamental to neuro-toxicity in Alzheimer’s disease. Metal ions can profoundly influence this misfolding pathway, while some proteins, in particular albumin catalase may be protective.
The aim of the work will be to understand the interaction of Aβ with lipid membranes and probe the effects of Aβ membrane composition on membrane disruption. You may also investigate how binding partners such as proteins and metal ions and co-seeding can affect the assembly of Aβ into toxic oligomers.
Methods and Training
You will use a large tool-kit of biophysical/ biochemical methods, imaging, spectroscopic and electrophysiology techniques to probe Aβ and lipid membrane interactions, as well as the kinetics of fibril formation. In particular: Electron Microscopy; Florescence; Circular Dichroism; AFM and NMR spectroscopy. In addition, you will gain experience in protein expression and purification.
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 with world class TEM, AFM, NMR, and CD facilities. Dr Viles has an outstanding track record in PhD student supervision - all past PhD students 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 Dr Viles' profile page.
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. Please see our entry requirements page for details.
The applicant must obtain an external source of funding.
Contact Dr Viles with a short E-mail, include the following:
1) Indicate the funding scheme you intend to apply, for which you are eligible.
2) Attach a two-page CV. Indicate any English Language qualifications you have and include Skype/MS-Team/whats-app contact details.
You may then wish to complete an online application form via the following link.
If your application is successful a conditional offer dependent of obtaining external funding will be made and Dr Viles will support you with in your application for funding and research proposal.
This project is open to applicants intending to personally apply for external funding. Offers made by Queen Mary will be conditional on you being successful in applying for external funding. For example, you may directly apply to the: China Scholarship Council, CONACYT (Mexico), Commonwealth Scholarships, Higher Education Commission (Pakistan). Please only apply if you are eligible through one of these schemes.
UK students should apply for PhD studentships that already have funding linked with them. If I am successful with ongoing grant applications, I will advertise the funded studentship separately, I currently have no funded PhD studentships available.