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

阐明 CHO 细胞中抗体产生和分泌的重要信号通路

• 批准号: 2467836
• 金额: --
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2467836
• 关键词: Elucidating; signalling; pathways; important; antibody

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.

组成型分泌是将新合成的蛋白质和脂质递送至细胞表面以及生理重要分子（例如抗体、细胞因子和细胞外基质蛋白）的胞吐作用所需的基本细胞过程。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，因此具有重要的财务重要性。在过去 40 年里，组成型分泌得到了广泛的研究，因此我们对作用于该途径的分子机制有了很好的了解。然而，目前尚不清楚这种机制是如何通过细胞外信号进行协调和调节的。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) 确定这些信号传导途径在 CHO 细胞抗体产生过程中如何变化，以及 3) 操纵这些途径以增强 CHO 细胞的抗体产生和性能。该项目将为葛兰素史克提供先进的质谱分析和最先进的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斯蒂夫尼奇葛兰素史克生物制药工艺研究中心之间的合作项目，因此学生将花费在公司工作了很长一段时间。候选人应拥有生物科学方面的强大学位。成功的候选人将积极主动，在团队环境中有效工作，并对细胞生物学、信号传导和生物制造感兴趣。该奖学金于 2020 年 10 月开始提供，是由 BBSRC 资助的为期 4 年的工业案例博士奖学金。学生资格申请人的资格标准可在 www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/ 上找到，您必须在申请前确认自己符合这些标准。