Using a global model of protein production with substrate competition to explain the complex mRNA vs. protein relationship arising from genetic perturbations

BIOT 276

Robert S. Kuczenski, rsk23@cornell.edu and Kelvin H. Lee, KHL9@cornell.edu. School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853-5201
With the exception of the most highly expressed genes, changes in mRNA expression are found to have a complex and nonlinear relationship to the resulting changes in protein expression. Thus, the predictable tuning of protein expression in genetic circuits, such as those found in synthetic biology, would benefit from an improved predictive capability. Here we present a cell-wide mathematical model of protein production which incorporates translation elongation rates, translation substrate competition (e.g. ribosomes), and mRNA degradation. We verify the model results by comparing the average translation elongation rate, protein production burst sizes, and mRNA decay rates to experimentally observed values. Finally, this model is tested to both qualitatively and quantitatively describe the experimentally observed relationship between changes in mRNA and protein expression in Escherichia coli.
 

Poster Session
5:30 PM-7:30 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007