BBSRC Industrial CASE studentship: Computational platform for antibody glycosylation prediction

Therapeutic glycoproteins represent 40% of biologics currently approved by the European Medicines Agency. These drugs are predominantly produced in mammalian cell hosts, such as Chinese hamster ovary (CHO) cells, which are capable of delivering high quality recombinant proteins with human-like post-translational modifications. One such modification is N-linked glycosylation, which involves the covalent addition of oligosaccharides to the protein backbone. It is well documented that these glycan structures can affect protein stability as well as efficacy and are therefore monitored during R&D and production. However, they have not traditionally been among the key performance indicators against which cell lines are screened during the early stages of cell line development campaigns. This is because of a variety of reasons ranging from the low culture volume at these stages, which does not allow extensive analytical characterisation of cells or product, to the cost of performing such analyses for a large number of samples.
Recently available instrumentation such as the Ambr system together with tools such as Raman spectroscopy are now enabling parallel experimentation with online or at line monitoring of cell population, nutrients and metabolites. This setup provides a more controlled environment than previous flask-based protocols and allows us to build more substantial and reliable databases to better understand these processes. We also have at our disposal a wealth of computational resources for data analysis as well as for mechanistically describing cellular behaviour. We can therefore envision a platform in which we track an increasingly large number of bioprocess parameters at low scale and feed these into computational platforms that generate predictions for difficult-to-measure but critical product properties.
The aim of this project is develop and validate this platform to support the development and selection of antibody-producing CHO cell lines. The specific project objectives are:
- To develop mathematical models for cell culture processes and use them for optimal experiment design;
- To validate the models for a wide range of experimental conditions that are commonly encountered in production reactors and for a range of cell lines;
- To create a user-friendly interface for use by cell culture scientists.
Student eligibility
Eligible applicants must be UK citizens or EU citizens who have been ordinarily resident in the UK for  3 years prior to the start of the grant. Applicants with or expecting a first (or upper second) class degree (or equivalent) in Chemical or Biochemical Engineering, Biotechnology or equivalent should send a C.V. and covering letter with contact details of two academic referees. A BBSRC Industrial CASE studentship provides funding for 4 years, during which the student must spend at least three months at the GSK site in Stevenage.

Industrial supervisor: Gary Finka, Biopharmaceuticals Director, Biopharm Process Research, GSK