MATHEMATICAL MODELING OF MAMMALIAN CELLS

THE RECENT DEVELOPMENT OF MOLECULAR BIOLOGY, PARTICULARLY INTHE FIELD OF RECOMBINANT DNA TECHNOLOGY, GIVES BIRTH TO A NEW ERA IN MEDICAL THERAPEUTICS AND DIAGNOSTICS USING PRODUCTS FROM MAMMALIAN CELL CULTURE. FOR EFFECTIVE RESEARCH AND CLINICAL USE, THESE PRODUCTS NEED TO BE MANUFACTURED IN LARGE QUANTITIES AND AT A TOLERABLE COST. TODAY PRODUCTION COSTS ARE VERY HIGH. THIS PROPOSAL IS PARTOF AN EXTENSIVE VERAX EFFORT TO REDUCE THE COST OF MASS CELLCULTURE BY A LARGE FACTOR. A MATHEMATICAL MODEL CAN BE A POWERFUL TOOL TO OPTIMIZE CULTURE PROCESSES. THIS PROPOSAL PRESENTS A PROJECT TO CREATE A MAMMALIAN-CELL MODEL WHICH WILL DESCRIBE QUANTITATIVELY THE EFFECTS OF ENVIRONMENTAL AND GENETIC VARIATIONS ON CELLULAR RESPONSE IN TERMS OF GROWTH, MORPHOLOGY, AND THE EXPRESSION OF CERTAIN GENE(S) OFINTEREST. SUCH A MODEL SHOULD BE USEFUL FOR DESIGN, CONTROL AND OPTIMUM OPERATION OF BIOLOGICAL REACTORS FOR THEBIOSYNTHESIS OF MAMMALIAN CELL PRODUCTS. IN PHASE II- EXPERIMENTS WILL BE CARRIED OUT IN ORDER TO TEST THE MODEL. BASED ON THE DATA AND MODEL PREDICTIONS, THE MODEL SYSTEM WILL BE FURTHER REFINED. AT THE END, OUR GOAL IS TO FORMULATE A STRUCTURED KINETIC MODEL OF MAMMALIAN CELLS WITH THE CAPABILITY TO PREDICT THE DYNAMIC BEHAVIOR OF CELL CULTURE OVER A WIDE RANGE OF CONDITIONS.