Protein synthesis, or translation, is one of the central intracellular processes. Understanding the properties of translation is extremely important for many problems in medical science and biotechnology, such as identification of antimicrobial targets, and optimization of pharmaceutical protein production. Translation involves three main steps: initiation, elongation, and termination. The proposed research is to characterize and understand quantitatively the mechanism of translation elongation in the bacterium Escherichia coli. A mechanistic, mathematical model of the elongation process will be developed, and the system properties will be characterized using mathematical and computational analysis. Experiments performed within the proposed work, as well as experimental data from literature, will provide estimates for the values of the kinetic parameters. Simulation studies will provide a deeper understanding of the systemic properties and the emerging behavior of protein synthesis. The proposed activity is a systems biology project at the interface of biochemistry, molecular biology, applied mathematics, and systems engineering. The expected outcome will enhance and broaden the understanding of the contribution of the individual steps of the elongation process in the context of the systemic properties of translation. The learning and the methodologies developed around translational elongation will be readily applicable to other template biopolymerization processes. The new knowledge and methods generated within the efforts of the proposed work will be incorporated in new and existing courses, such courses on Computational Biology and Bioinformatics. The proposed activities will train a new generation of biologists, mathematicians, and engineers that will be able to creatively apply the engineering principles on complex biological systems for the analysis and interpretation of experimental information from modern biochemical and molecular biology methodologies.
