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PhD Studentship: Antibody Design for Tau Oligomers


Applications are invited for an MRC PhD studentship in the Department of Chemistry in the Centre for Misfolding Diseases supervised by Professor Michele Vendruscolo and Professor David Klenerman. The studentship is available from October 2017, and is a multi-disciplinary project that aims to develop antibodies against the aggregation of the protein tau, which is closely associated with Alzheimer's disease and related neurodegenerative disorders. The main focus will be on targeting the small tau oligomers that form during the aggregation process of this protein, as these species are widely considered to be the most toxic ones for neurons.

The antibodies will be created by using a computational approach recently developed by the Vendruscolo group, which is based on in silico design and offers novel opportunities to target tau oligomers compared with more traditional in vitro and in vitro methods. The main advantage of this approach is the ability to produce a panel of antibodies to scan different epitopes to cover the whole sequence of tau. This approach has been recently demonstrated for the Abeta peptide (Science Advances, in press), which is also associated with Alzheimer's disease, and has provided antibodies capable of blocking both the formation and the toxicity of Abeta oligomers. We are therefore interested in finding out whether similar results can be obtained for tau.

The ability of the antibodies to block the toxicity of tau oligomers will be verified using a series of assays recently developed by the Klenerman group, including single aggregate imaging and measuring their ability to bind tau aggregates in vivo and in ex vivo samples, to disrupt cell membranes and to trigger the immune response.

Applicants should have (or expect to obtain) the equivalent of a UK first class or upper second class honours degree (and preferably a Masters degree) in physics, chemistry, biochemistry or other relevant discipline, and have an interest in performing multi-disciplinary research. The studentship provides a maintenance grant and tuition fees at the UK/EU rate. Applicants must satisfy the eligibility and residence requirements of the UK Research Councils. Owing to restrictions imposed by the sponsor, non-EU citizens cannot be considered.

Applications should emailed to Sharon Connor (email: sc867@cam.ac.uk), and should include a CV, detailed academic transcripts, a cover letter highlighting what you can bring to the project, and the contact details for two academic referees. For informal enquiries please contact Professor Vendruscolo (email: mv245@cam.ac.uk).

Please quote reference MA12357 on your application and in any correspondence about this vacancy.