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

点击翻译按钮获取中文摘要

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.