Engineering of synthetic genetic circuits holds the promise to revolutionize medical treatment and industrial production from microbes. Yet progress over the last decade has been hindered by a lack of rational design principles to guide the interfacing of engineered components with the host organism. Recent work demonstrates that even constitutive protein expression, and much more so genetic circuits, can be strongly affected by the cell’s physiological state. Thus, it appears difficult to insulate synthetic circuitry from the growth state of the host. Despite the inherent crosstalk between synthetic and endogenous elements, some of the resultant global effects have been shown to obey simple mathematical relations referred to as “growth laws”. These quantitative relations may provide a framework for the design of robust synthetic systems, opening up new directions in bioengineering and biotechnology.
Bacterial growth laws and their applications. Curr Opin Biotechnol. May 16 2011
Quantitative empirical relationships between cell composition and growth rate played an important role in the early days of microbiology. Gradually, the focus of the field began to shift from growth physiology to the ever more elaborate molecular mechanisms of regulation employed by the organisms. Advances in systems biology and biotechnology have renewed interest in the physiology of the cell as a whole. Furthermore, gene expression is known to be intimately coupled to the growth state of the cell. Here, we review recent efforts in characterizing such couplings, particularly the quantitative phenomenological approaches exploiting bacterial ‘growth laws.’ These approaches point toward underlying design principles that can guide the predictive manipulation of cell behavior in the absence of molecular details.