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Novel adjuvants for antibody-based cancer therapeutics: design, biological characterization and influence on membrane-protein structure

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  • Full or part time
    Dr Doryen Bubeck
    Prof E Tate
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Cancer Research UK Imperial Centre
PhD Studentship in Structural Biology
Imperial College London
South Kensington Campus, London, UK

Title:
Novel adjuvants for antibody-based cancer therapeutics: design, biological characterization and influence on membrane-protein structure

Supervisors:
Dr Doryen Bubeck (Department of Life Sciences), Prof Ed Tate (Department of Chemistry)

The Project:
Monoclonal antibodies (mAbs) are one of the most exciting new classes of anticancer agent, with a current market of over $20 billion forecast to grow by 50% in the next 3 years. The mechanism by which mAbs kill cancer cells during cancer immunotherapy treatments is complex, and involves the interplay of multiple effectors, including selective activation of complement-dependent cytotoxicity (CDC). Membrane attack complex (MAC) pores contribute to CDC, and are counteracted by membrane-bound complement inhibitors such as CD59, which are overexpressed on tumor cells and can provide a mechanism for immune evasion. Interestingly, bacterial pore-forming toxins with a similar structural fold to MAC proteins (e.g. Streptococcus Intermedilysin, ILY) compete for CD59-binding through a specific interface, and increase cells’ susceptibility to CDC. This project will integrate a platform of technologies to determine how MAC pores lyse cells and how CD59 regulates this process, providing fundamental insights into the mechanism of action of rituximab. This platform will be exploited to design and optimize compounds that can specifically block CD59, and thus potentiate anticancer immunotherapy.

The project would ideally suit an outstanding biochemistry graduate with some existing experience in protein chemistry and/or structural biology. You should also have a strong interest in structural and functional characterisation of protein complexes and protein-drug interactions, and in developing and applying these methods in the context of cancer treatment. The successful candidate will receive training in all relevant aspects of protein chemistry, biophysics and structural biology.

For informal enquiries please contact Dr Doryen Bubeck ([Email Address Removed]).

TO APPLY: please send a letter of motivation, your full CV which includes your nationality and the full contact details of two academic referees to [Email Address Removed]

We regret that due to the large volume of applications received, we are only able to notify those shortlisted for interview. The deadline for applications is January 15, 2018.

Funding Notes

This studentship is fully funded by Cancer Research UK for 48 months (full time) and covers fees at Home/EU rates and tax-free stipend of £21,000 annually. Applicants must hold (or obtain by October 2018) a First Class or Upper Second Class degree (or equivalent overseas qualification) in Biochemistry; Imperial would normally expect successful applicants to hold or achieve a relevant Master's degree.
Prior experience in cryo electron microscopy is not essential but experience protein chemistry and/or structural biology techniques would be preferred.
Non-EU applicants will be responsible for fees at the overseas rate (£36,100/year). Overseas fees not provided.



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