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Protein Misfolding and the Molecular Basis of Alzheimer’s Disease

  • Supervisor: Dr John Viles
  • Deadline for Ciência sem Fronteiras funding: None
  • Deadline for CONACYT funding: None
  • Deadline for China Scholarship funding: Applications for 2015 entry have now closed. To express your interest in this project for 2016 please contact the project supervisor
  • Funding: China Scholarship Council, CONACYT and Ciência sem Fronteiras

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 early stages of the amyloid cascade are characterised 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;

  1. A vesicle model of membrane permeability
  2. Measurements of synaptic health
  3. Toxicity in Drosophila models
  4. Cell viability

Environment and support

Queen Mary 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) Dr Viles' lab has 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.

Eligibility and applying

Funding through China Scholarship Council

  • Eligibility

Applicants should be Chinese nationals and are required to have at least an upper second class degree and a masters degree in a related discipline from a top university anywhere in the world.

International students must provide evidence of proficient English language skills, see our entry requirements page for further information.

  • Applying

Applications for 2015 entry have now closed. To express your interest in this project for 2016 please contact the project supervisor Dr Viles by e-mail (j.viles@qmul.ac.uk)

Dr Viles will then ask you to submit your CV (including details of two referees) and a cover letter explaining your eligibility and interest in this project.

If you are successful we will give you an offer on the condition that you are given a funding award from the China Scholarship Council. When you have received a conditional offer, you will need to apply directly to the China Scholarship Council.

Funding through CONACYT

  • Eligibility

Applicant requirements are listed on the CONACYT foreign scholarship pages.

International students must provide evidence of proficient English language skills, see our entry requirements page for further information.

  • Applying

Potential candidates should contact Dr Viles by e-mail (j.viles@qmul.ac.uk) and submit their CV (including details of two referees) and a cover letter explaining their eligibility and interest in this project.

If you are successful we will give you an offer on the condition that you are given a funding award from CONACYT. When you have received a conditional offer, apply directly to CONACYT.

Applications to Queen Mary are accepted all year round but we encourage you to contact Dr Viles as soon as possible. If he agrees to take your application further you will be required to submit an online application.

Funding through Ciência sem Fronteiras

  • Eligibility

Applicants must be Brazilian nationals and are required to have at least an upper second class degree and a masters degree in a related discipline from a top university anywhere in the world. For more information visit the Ciência sem Fronteiras eligibility pages.

International students must provide evidence of proficient English language skills, see our entry requirements page for further information.

  • Applying

Potential candidates should contact Dr Viles by e-mail (j.viles@qmul.ac.uk) and submit their CV (including details of two referees) and a cover letter explaining their eligibility and interest in this project.

Applications to Queen Mary and Ciência sem Fronteiras are accepted all year round but we encourage you to contact Dr. Viles as soon as possible.

If you are successful we will give you an offer on the condition that you are given a funding award from Ciência sem Fronteiras. When you have received a conditional offer, apply directly to Ciência sem Fronteiras.

Self-funding

If you are interested in self-funding please contact Dr Viles by e-mail (j.viles@qmul.ac.uk) to discuss your eligibility for this project.
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