The aim of the proposed research is to distinguish among three competing models (exponential, linear, or bilinear growth) for the kinetics of cell growth in Escherichia coli or to determine the actual growth kinetics if none of the three models fit. Each of these models implies different mechanisms for the control of cell growth. Despite its significance, little is known about the mechanisms by which cell growth is controlled, how individual cells control increases in their own different macromolecular components, and how these controls are coordinated. Knowledge of these control mechanisms would have far-reaching implications for such diverse areas of biological importance as embryology and tumorigenesis and should lead to identification of biosynthetic mechanisms that will allow the design of superior antibiotics and antitumor agents. Three experimental approaches are proposed for use with synchronized cultures. We propose to determine (1) increase in mean cell mass from measurements of mean cell volume and buoyant density; (2) kinetics of accumulation of precursor pools and macromolecular cell fractions for the three largest macromolecular classes: protein, RNA, and lipid; and (3) kinetics of net rates of uptake of precursors specific for these macromolecules. With each method, data will be obtained at several growth rates. We expect to identify a model that is independent of the experimental approach and applicable at all growth rates. This identification should provide strong impetus for the design of future experiments that reveal the detailed nature of the physiological and biosynthetic processes critical in the control of cell growth.
| Pai, S R; Kubitschek, H E (1991) The phosphate pool in Escherichia coli THU. FEMS Microbiol Lett 65:49-51 |
| Kubitschek, H E; Pai, S R (1988) Variation in precursor pool size during the division cycle of Escherichia coli: further evidence for linear cell growth. J Bacteriol 170:431-5 |
| Kubitschek, H E (1986) Increase in cell mass during the division cycle of Escherichia coli B/rA. J Bacteriol 168:613-8 |
