High-performance glycoengineering of IgE antibodies
Dr Gerd Wagner, Department of Chemistry, King's College London
Dr Sophia Karagiannis, St John’s Institute of Dermatology, King's College London
Dr Jenifer Hendel, Ludger Ltd (Abingdon)
Dr Louise Royle, Ludger Ltd (Abingdon)
BACKGROUND. Immunoglobulin E (IgE)-based antibodies are currently under investigation as novel immunotherapeutics for the treatment of cancer . IgE is a heavily glycosylated glycoprotein, whose glycans make up more than 10% of its molecular mass . Manipulating the glycan structure of IgE therefore offers a unique opportunity to improve the clinical performance of IgE-based antibodies. However, while it is clear that the number and nature of IgE glycans significantly affect the biological and pharmacological activity of IgE-based antibodies, it is not clear, how.
THE PROJECT. In this project, you will elucidate the effect of IgE glycan structure on the anti-cancer activity of IgE-based antibodies. You will chemically synthesise a set of unique glycosylation inhibitors  and use them in conjunction with established IgE culture systems  to generate defined IgE glycoforms. You will characterise your IgE glycoforms in a range of bioassays to establish relevant properties such as stability, antigen and receptor binding, IgE-mediated signalling and tumour cell killing, apoptosis, proliferation and viability. Finally, you will determine the glycan structure of your IgE glycoforms and identify the structural basis for the observed biological and pharmacological activities.
IMPORTANCE. If successful, your research will lead to novel IgE-based therapeutics for anti-cancer therapy and establish a new, general strategy for the high-performance glycoengineering of therapeutic antibodies.
TRAINING. This highly interdisciplinary project will provide training in a broad range of techniques relevant to biotechnology and bioengineering, including chemical synthesis, cell culture work and monoclonal antibody production, biological and pharmacological assays, and cutting-edge glycoanalysis.
INDUSTRIAL PARTNER. The project will be carried out in collaboration with Ludger Ltd, a world-leading glycomics company, who will host the student for two 3-month placements. Ludger will provide access to their unique glycoanalytics technology for the structural characterisation of the IgE glycoforms, as well as comprehensive training in relevant experimental techniques and business-related transferable skills.
KEYWORDS: therapeutic antibodies, bioengineering, inhibitor, synthesis, glycan
This project would be ideally suited for a student with a background in chemical biology, chemistry or a related subject, who wants to broaden their skill set in biology, biotechnology and bioengineering. It may also be suitable for a biology/biotechnology student with a strong interest and, ideally, previous experience, in biological or synthetic chemistry.
Applicants must hold, or be expected to achieve, a first or high upper second-class undergraduate honours degree or equivalent (for example BA, BSc, MSci) or a Masters degree in a relevant subject. Interested applicants are encouraged to contact Gerd Wagner (firstname.lastname@example.org) in advance of the deadline, 20th January 2017 at 5pm.
This project offers an enhanced stipend in the region of £17,296 per annum.
To apply you will need to send the following documents in a single email to: LIDo.Admissions@ucl.ac.uk. All documents must be submitted in unprotected PDF format.
- Completed Application Form (Sections A and B) including details of two Academic References
- The disability and ethnic origin monitoring form
- Official Final Transcripts from Completed Programmes of Study
- Official Interim Transcripts from On-going Programmes of Study
- English Language Qualification (if required, please see below)
- Academic CV
- Copy of Passport
- Josephs DH, Spicer JF, Karagiannis P, Gould HJ, Karagiannis SN. IgE immunotherapy: a novel concept with promise for the treatment of cancer. MAbs 2014, 6, 54.
- Plomp R, Hensbergen PJ, […] Wuhrer M. Site-Specific N‑Glycosylation Analysis of Human Immunoglobulin E. J. Proteome Res. 2014, 13, 536.
- Pesnot T, Jorgensen R, Palcic MM, Wagner GK. Structural and mechanistic basis for a new mode of glycosyltransferase inhibition. Nat. Chem. Biol. 2010, 6, 321.
- Dodev TS, Karagiannis P, […] Karagiannis SN, Beavil AJ. A tool kit for rapid cloning and expression of recombinant antibodies. Sci. Rep. 2014, 4, 5885.