High-performance glycoengineering of IgE antibodies

Immunoglobulin E (IgE)-based antibodies are currently under investigation as novel immunotherapeutics for the treatment of cancer [1]. IgE is a heavily glycosylated glycoprotein, whose glycans make up more than 10% of its molecular mass [2]. 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 [3] and use them in conjunction with established IgE culture systems [4] 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. The project is particularly suited for a student with a background in chemistry or chemical biology, who wants to learn new skills in biotechnology, cell biology and bioanalytics.

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.

Application Deadline
Applications must be complete, including references, by 11th January 2019 at 5pm