SYSTEMS BIOLOGY OF OSMOTIC SHOCK IN ANTIBODY

This doctoral candidacy proposal is comprised of proposed work and current progress toward a doctoral dissertation in Multidisciplinary Science. Osmolarity has a significant impact on the growth and productivity of industrial mammalian cell cultures. Over the course of a fed-batch culture the osmolarity can increase from ~290mOsm/kg to 500mOsm/kg (Zhu 2005). Osmolarity increases of this magnitude are detrimental to mammalian cell cultures, reducing viability by as much as 50 % (Kurano 1990). However, increases in osmolarity can increase specific production rates of antibodies and other recombinant proteins by as much as twofold (Ozturk 1991). In order to engineer mammalian cells for optimal recombinant protein production it is necessary to have a full understanding of the cellular response to osmotic stress. Recent literature has shown the importance of the transcription factor TonEBP/NFAT5/OREBP in the cellular response to osmotic shoc