Developing novel biosensors for monitoring antibody production in CHO cells.

生物制药市场每年价值超过1000亿美元，其中大多数治疗性抗体是在中国卵巢（CHO）细胞中生产的。然而，产生适于商业生产的单克隆抗体（mAb）生产细胞系的方法仍然具有挑战性、耗时且昂贵。在过去的10年中，对支持CHO细胞中抗体产生的细胞途径进行了广泛研究;然而，仍不清楚哪些途径对该过程最重要（蛋白质折叠、蛋白质转运和细胞应激）。该博士学位的目的是通过研究生产和分泌单克隆抗体的CHO细胞系的细胞内表型，促进对CHO mAb生产细胞系的更深入了解。利用所获得的知识，我们的目标是定义与有利的制造和产品质量特征相关的表型指纹。一旦确定了这些指纹，将开发一系列用于监测它们的新型荧光工具，并将其应用于我们的细胞系开发平台，以便在细胞系开发的最早阶段筛选最佳mAb生产细胞系。该项目将提供先进的哺乳动物细胞培养、荧光显微镜、流式细胞术方面的培训，并提供GSK实验室现有的最先进、高通量、自动化细胞培养系统（Berkeley Lights Beacon）和表型分析系统（Intellicyt iQue）。

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.