Modeling of Hybridoma Cell Growth and Manipulation of its Physiological State

9727269 Hu PI的Hu和Ramkrishna是哺乳动物细胞培养和代谢建模各自领域的专家。 该建议结合了这些互补的专业领域，试图了解杂交瘤培养中的蛋白质生产力因素。 该假说是，细胞代谢可以被操纵，以通过最小化非生产性细胞代谢状态来最大化该过程的效率。 该提案的具体目的是定义导致不同代谢状态的培养条件，确定通过改变葡萄糖和谷氨酰胺的浓度引起的变化，并在稳态和变化条件下对这些不同状态进行代谢通量分析。 将开发一个控制论模型来描述在限制环境条件下的这些不同状态，例如，葡萄糖和谷氨酰胺的可用性，并考虑状态之间的切换。 然后将建立使抗体生产率最大化的反应器条件。 ***

9727269 Hu The PI's Hu and Ramkrishna, are experts in their respective fields of mammalian cell culture and metabolic modeling. This proposal combines these complimentary areas of expertise in an attempt to understand the protein productivity factors in hybridoma cultures. The hypothesis is that cellular metabolism can be manipulated to maximize the efficiency of the process by minimizing non-productive cell metabolic states. The specific aims of the proposal are to define the conditions of the cultures that lead to the different metabolic states, to determine what changes are induced by varying the concentrations of glucose and glutamine, and to perform metabolic flux analysis of these different states under steady state and changing conditions. A cybernetic model will be developed to describe these different states under limiting environmental conditions, e.g., glucose and glutamine availability and to account for switching between states. Reactor conditions will then be established which maximize antibody productivity. ***