Elucidating the signalling pathways important for antibody production and secretion in CHO cells

组成性分泌是一个基本的细胞过程，用于将新合成的蛋白质和脂质输送到细胞表面，以及分泌生理上重要的分子，如抗体、细胞因子和细胞外基质蛋白。该途径在所有细胞类型中都是保守的，并支持CHO细胞的生物制造，因此具有重要的经济意义。在过去的40年里，人们对组成分泌进行了广泛的研究，因此我们对作用于这一途径的分子机制有了很好的了解。然而，这种机制是如何通过细胞外信号进行协调和调节的，目前还不清楚。该项目的总体目标是：1)确定哪些细胞外信号调节抗体的产生和分泌；2)确定这些信号通路在CHO细胞抗体产生过程中是如何变化的，3)操纵这些通路以增强CHO细胞的抗体产生和性能。该项目将为gsk提供先进的质谱和高通量自动化细胞培养和表型分析系统的培训。该项目是谢菲尔德大学和葛兰素史克生物制药工艺研究公司的合作项目，因此学生将在该公司度过一段很长的时间。候选人应具有较强的生物科学学位。工作积极主动，在团队中高效工作，对细胞生物学，信号和生物制造感兴趣。该奖学金从2020年10月开始提供，是bbsrc资助的4年工业案例博士奖学金。申请人的资格标准可以在www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/上找到，你必须在申请之前确定你符合这些标准。

Constitutive secretion is a fundamental cellular process required for the delivery of newlysynthesised proteins and lipids to the cell surface as well as the exocytosis of physiologicallyimportant molecules such as antibodies, cytokines and extracellular matrix proteins. This pathwayis conserved in all cell types and underpins biomanufacturing in CHO cells so has significantfinancial importance. Constitutive secretion has been extensively studied over the last 40 years sowe have a good understanding of the molecular machinery that acts on this pathway. However, itis not well understood how this machinery is coordinated and regulated by extracellular signals.The overarching aims of this project are to: 1) identify which extracellular signals regulate antibodyproduction and secretion; 2) determine how these signalling pathways change during antibodyproduction in CHO cells and 3) manipulate these pathways to enhance antibody production andperformance of CHO cells. This project will provide training in advanced mass-spectrometry andstate of the art, high-throughput, automated systems for cell culture and phenotypic analysis atGSK.This project is a collaboration between the University of Sheffield and GSK BiopharmaceuticalProcess Research, Stevenage so the student will spend a significant period of time based with thecompany. Candidates should have a strong academic degree in biological sciences. Thesuccessful candidate will be highly motivated, work effectively in a team setting and be interestedin cell biology, signalling and biomanufacturing. This studentship is available starting October 2020and is a 4 year BBSRC-funded Industrial CASE PhD studentship. Applicant eligibility criteria for thestudentship can be found at www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/ and you mustidentify that you fit these criteria prior to application.