Modeling of Hybridoma Cell Growth and Manipulation of its Physiological State

9727269胡，派的胡和拉姆克里希纳，是各自领域的哺乳动物细胞培养和代谢建模专家。这项建议结合了这些互补的专业知识领域，试图了解杂交瘤培养中的蛋白质生产力因素。假设细胞代谢可以通过最小化非生产性细胞代谢状态来最大限度地提高该过程的效率。该提案的具体目的是确定导致不同代谢状态的培养条件，确定不同浓度的葡萄糖和谷氨酰胺会引起什么变化，并在稳定状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，以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，并解释状态之间的切换。然后将建立最大限度地提高抗体产量的反应条件。***

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. ***