A defining component of Synthetic Biology is the development of theoretical modeling that can serve as the foundation for a new type of cellular engineering.  This talk will be anchored by my quest to build genetic oscillators in bacteria, with a particular focus on the utility of theory and computation.  I’ll start by describing how the coupling of transcriptional activators and repressors was originally modeled as a type of classical “predator-prey” system.  Although this system led to the design of a robust intracellular clock (http://biodynamics.ucsd.edu/Intracellular.mov), I’ll show how the experiments pointed to a different type of “degrade and fire” oscillator characterized by a coupled set of delayed differential equations. Interestingly, the biological constraints naturally lead to a system that can be solved approximately.  In terms of engineering, the clock was not of the Swiss variety; the period and amplitude exhibited large intracellular variability.

However, it provided a benchmark for the development of general synchronization strategies that can restore determinism. I’ll conclude with our efforts to use cellular communication to couple clocks between cells (http://biodynamics.ucsd.edu/Intercellular.mov) and colonies (http://biodynamics.ucsd.edu/Intercolony.mov). Here, the threshold nature of the communication mechanism leads naturally to oscillators that are highly reminiscent of “integrate and fire” systems in neuroscience.