Developing novel biosensors for monitoring antibody production in CHO cells.

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The biopharmaceutical market is valued at over 100 billion dollars per year with the majority of therapeutic antibodies being manufactured in Chinese Hamster Ovary (CHO) cells. However, the process of generating monoclonal antibody (mAb) producing cell lines suitable for commercial manufacture remains challenging, time consuming and costly. The cellular pathways underpinning antibody production in CHO cells have been extensively studied over the past 10 years; however, it is still unclear which pathways are most important for this process (protein folding, protein transport and cell stress). The aim of this PhD is to facilitate a deeper understanding of CHO mAb production cell lines by investigating the intracellular phenotypes of CHO cell lines which are producing and secreting monoclonal antibodies. Using the knowledge gained we aim to define a phenotypic fingerprint which correlates with favourable manufacturing and product quality characteristics. Once these fingerprints have been defined, a series of novel fluorescent tools for monitoring them will be developed and applied to our cell line development platform to allow screening for optimal mAb producing cell lines in the earliest stages of cell line development. This project will provide training in advanced mammalian cell culture, fluorescence microscopy, flow cytometry and access to state of the art, high-throughput, automated systems for cell culture (Berkeley Lights Beacon) and phenotypic analysis (Intellicyt iQue) in place at the GSK laboratories.