A novel approach to Biopharm cell line selection using advanced molecular microscopy and chemical profiling

培养的细胞系在制药工业中具有生产生物治疗剂的巨大潜力。我们对“生产者”细胞系内各种生物过程的细胞、代谢和遗传机制的理解还没有完全理解。目前正在整个行业探索识别这些细胞特性并将其与生物加工表型联系起来的努力，以优化生物素生产。光学显微镜是细胞生物学中不可或缺的工具，并且仍然是以高空间和时间分辨率破译活细胞中生物分子和小分子化合物的细胞位置，功能和相互作用的唯一实用方法。光学显微镜技术领域内的进步已经使得新一代的显微镜能够被开发，其允许细胞的化学成分被可视化而不需要染色或操作。相干反斯托克斯拉曼散射（汽车）结合了拉曼光谱的化学特异性和多光子显微镜的固有光学切片，该项目涉及分子成像方法和图像分析能力的应用，以可视化细胞内和细胞外代谢物，定位蛋白质表达和识别表达外源蛋白质的关键因素。通过将这些技术应用于显示差异表型的细胞系，我们可以将基于图像的数据集与过程性能相关联，并识别细胞现象，例如细胞器丰度，蛋白质运输，分泌瓶颈和固有的生化概况。这4-为期一年的博士研究生是一个合作项目，涉及GSK和卡迪夫大学的综合专业知识，以更深入地了解细胞特性，使用专业和先进的显微镜技术。该项目旨在开发和嵌入特定的生物成像技术在早期阶段的细胞系开发。这个学生是跨学科的性质，因此将适合从物理和生命科学的毕业生。作为该项目的一部分，学生将在GSK度过至少3个月的时间，在4年的时间里获得工业环境中的研究经验。

Cultured cell lines have great potential within the pharmaceutical industry for the production of biotherapeutics. Our understanding of the cellular, metabolic and genetic mechanisms underpinning various biological processes within "producer" cell lines are not fully understood. Current efforts to identify and link these cellular properties to bioprocessing phenotypes are being explored across the industry in order to optimise biotherapeutic production. Optical microscopy is an indispensable tool in cell biology and is still the only practical way to decipher the cellular location, function and interactions of biomolecules and small molecular compounds in living cells with high spatial and temporal resolution. Advances within the field of optical microscopy technologies have enabled a new generation of microscopes to be developed that allow the chemical components of a cell to be visualised without the need of staining or manipulation. Coherent anti-Stokes Raman scattering (CARS), combines the chemical specificity of Raman spectroscopy with the intrinsic optical sectioning of multiphoton microscopy.This project involves the application of molecular imaging methodologies and image analysis capabilities to visualise intra and extra-cellular metabolites, localise protein expression and identify key factors for expressing exogenous proteins. Through applications of these techniques to cell lines displaying differential phenotypes, we can correlate image-based data-sets with process performance, and identify cellular phenomena such as organelle abundance, protein trafficking, secretion bottlenecks and inherent biochemical profiles.This 4-year PhD studentship is a collaborative project involving the combined expertise of GSK and Cardiff University to gain deeper understanding of cellular characteristics using specialised and advanced microscopy techniques. This project aims to develop and embed specific Bio-imaging techniques within early stage cell line development.This studentship is cross-disciplinary in nature, and so would suit graduates from both the physical and life sciences. As part of the project the student will spend a minimum of 3 months at GSK, to gain research experience in an industrial setting, over the course of 4 years.