Figure 1.

A computational framework for the rational design of synthetic cells with prescribed population dynamics. From a conceptual experiment design (a) we program a system design of the genetic device (b) using the genetic engineering of cells (GEC) language. Following compilation of the design to a set of genetic devices (c; shown as a representative plasmid), we select a candidate device and compile it to a system model (d), which characterizes the intracellular dynamics of the device. We then obtain a reduced system model (e) as a set of ordinary differential equations (ODEs), under quasi-steady-state assumptions (QSSAs). We then incorporate population factors to obtain a population model (f). We conduct parameter scans to identify the environmental conditions that generate the desired population dynamics (g). We then vary the parameters of the system to further improve the population dynamics under the chosen environmental conditions (h). The parameter scans are then used to constrain the system design, by restricting the kinetic properties of the biological parts that can be selected. We then simulate a candidate device that satisfies the design constraints, using full spatio-temporal simulations (i). The candidate device can then be synthesized and tested in the laboratory.