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(A*STAR) Engineering the recognition of antibodies by bacterial superantigens


Project Description

Superantigens are proteins which have the ability to cause hyperactivation of T cells; they are produced by certain bacteria or viruses as a defence mechanism against attack by the immune system. Some superantigens can, however, be adapted for useful purposes. Protein A from S. aureus, for example, is widely used for purification of antibodies. However, the reasons behind the precise specificity of Protein A-antibody binding is enigmatic, as not all antibodies recognise Protein A. The development of a wide range of protein A variants that can bind to specific variable regions of the antibodies would therefore have significant uses for antibody purification as well as potential therapeutic purposes for specific inactivation of antibodies or B cells. This project will structural and protein engineering methods to adapt and modify the binding of Protein A, and two other antibody-binding proteins from bacteria, Protein L and Protein G, to the variable domains of antibodies. The project would particularly suit a student with a background in biotechnology, biochemistry or a related subject, who has an interest in protein engineering and its application to the therapeutic antibody industry.

Entry Requirements:
Applications should be submitted online and candidates should make direct contact with the Manchester supervisor to discuss their application directly. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is available to UK/EU candidates. Funding covers fees (UK/EU rate) and stipend for four years. Overseas candidates can apply providing they can pay the difference in fees and are from an eligible country. Candidates will be required to split their time between Manchester and Singapore, as outlined on View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Lua W-H, Su CT-T, Yeo JY, et al. Role of the IgE variable heavy chain in FcεRIα and superantigen binding in allergy and immunotherapy. J Allergy Clin Immunol 2019;144(2):514-23.e5. doi: 10.1016/j.jaci.2019.03.028

Su, C.T., Ling, W., Lua, W. et al. The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding. Sci Rep 7, 3766 (2017) doi:10.1038/s41598-017-02756-3

Salleh M, Karuppiah V, Snee M, et al. Structure and properties of a natural competence-associated pilin suggest a unique pilus tip-associated DNA receptor. mBio 2019;10(3):e00614-19.

Collins R, Karuppiah V, Siebert CA, et al. Structural cycle of the Thermus thermophilus PilF ATPase: the powering of type IVa pilus assembly. Scientific Reports 2018;8(1):14022. doi: 10.1038/s41598-018-32218-3

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