About the Project
Academic supervisors: Dr Gerd Wagner & Dr Sophia Karagiannis (King’s College London)
http://www.kcl.ac.uk/nms/depts/chemistry/people/core/wagnergerd/index.aspx
Industrial partner: Ludger Ltd (Abingdon)
http://www.ludger.com
A fully funded PhD position is available in the group of Dr Gerd Wagner (King’s College London, Department of Chemistry), for a project at the interface of biotechnology and chemistry. The position is fully funded for 4 years through a BBSRC Industrial Case studentship. The project will involve close collaboration with Dr Sophia Karagiannis (King’s College London, St John’s Institute of Dermatology) and an industrial partner, Ludger Ltd (Abingdon). Opportunities for several industrial research placements will be provided.
BACKGROUND. 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.
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.
ELIGIBILITY. 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.
STIPEND. £17,296 per annum. NB that funding is available for Home/EU students ONLY.
APPLICATION PROCESS. The deadline for applications is 20th January 2017 at 5pm.
For details of the application process, please contact Dr Gerd Wagner ([Email Address Removed]) well in advance of the deadline.
KEYWORDS: therapeutic antibodies, bioengineering, inhibitor, synthesis, glycan
SUBJECT AREAS: chemistry, chemical biology, biotechnology, bioengineering, biology
References
REFERENCES
[1] 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.
[2] Plomp R, Hensbergen PJ, […] Wuhrer M. Site-Specific N‑Glycosylation Analysis of Human Immunoglobulin E. J. Proteome Res. 2014, 13, 536.
[3] 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.
[4] Dodev TS, Karagiannis P, […] Karagiannis SN, Beavil AJ. A tool kit for rapid cloning and expression of recombinant antibodies. Sci. Rep. 2014, 4, 5885.