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. ***
