Research Initiation: Investigation of the Mechanisms Responsible for Increased Antibody Production by Hybridomas Exposed to Stress

研究启动奖：应激下杂交瘤抗体产生增加的机制研究单克隆抗体是利用哺乳动物细胞制造的产量最大的产品之一。据报道，暴露于环境胁迫下的杂交瘤抗体产生增加。这个项目的目标是描述负责增加抗体生产的机制，并确定提高生产效率的反应器条件。将监测能量代谢和DNA合成的同步变化，以确定细胞生长、能量产生和蛋白质表达调节之间的相互关系。为了将细胞生长与产物形成分离开来，需要了解这些关系。过度的细胞生长是不希望的，因为昂贵的培养基浪费在生产生物质。降低细胞生长速率也是可取的，因为许多原代、杂交和基因改变的细胞系在重复细胞分裂后降低了它们的产物形成速率。

RESEARCH INITIATION AWARD: INVESTIGATION OF THE MECHANISMS RESPONSIBLE FOR INCREASED ANTIBODY PRODUCTION BY HYBRIDOMAS EXPOSED TO STRESS ABSTRACT Monoclonal antibodies are among the largest-volume products made using mammalian cells. Increased antibody production has been reported for hybridomas exposed to environmental stress. The objectives of this project are to characterize the mechanisms responsible for increased antibody production, and to identify reactor conditions with increased productivity. Concurrent changes in energy metabolism and DNA synthesis will be monitored in order to determine the interrelationships between the regulation of cell growth, energy production and protein expression. An understanding of these relationships is required in order to decouple cell growth from product formation. Excessive cell growth is not desired because expensive medium is wasted on the production of biomass. Reduced cell growth rates are also desirable because many primary, hybrid, and genetically- altered cell lines decrease their rate of product formation after repeated cell divisions.