Computational Methods in Synthetic Biology

Wilson-Kanamori, John, Danos, Vincent, Thomson, Ty, Honorato-Zimmer, Ricardo, John Wilson-Kanamori, Vincent Danos, Ty Thomson, Ricardo Honorato-Zimmer

Marchisio, Mario Andrea

Rule-based modeling, an alternative to traditional reaction-based modeling, allows us to intuitively specify biological interactions while abstracting from the underlying combinatorial complexity. One such rule-based modeling formalism is Kappa, which we introduce to readers in this chapter. We discuss the application of Kappa to three modeling scenarios in synthetic biology: a unidirectional switch based on nitrosylase induction in Saccharomyces cerevisiae, the repressilator in Escherichia coli formed from BioBrick parts, and a light-mediated extension to said repressilator developed by the University of Edinburgh team during iGEM 2010. The second and third scenarios in particular form a case-based introduction to the Kappa BioBrick Framework, allowing us to systematically address the modeling of devices and circuits based on BioBrick parts in Kappa. Through the use of these examples, we highlight the ease with which Kappa can model biological interactions both at the genetic and the protein-protein interaction level, resulting in detailed stochastic models accounting naturally for transcriptional and translational resource usage. We also hope to impart the intuitively modular nature of the modeling processes involved, supported by the introduction of visual representations of Kappa models. Concluding, we explore future endeavors aimed at making modeling of synthetic biology more user-friendly and accessible, taking advantage of the strengths of rule-based modeling in Kappa.