9402030 Miller This project is on research to examine the effects of low oxygen levels and high carbon dioxide levels on Chinese Hamster Ovary (CHO) cell growth and metabolism, tissue plasminogen activator (tPA) synthesis, glycosylation, and proteolysis. This project will also attempt to characterize the mechanisms responsible for changes in tPA quality, and address problems that are encountered in the large scale production of therapeutic proteins by mammalian cell culture. ***