Co-Design of Resource Limited Genetic Modules

Modular composition of systems through defined input/output interfaces is a wide- spread engineering approach that allows to make the design of complicated systems tractable. Although this approach has percolated to the design of synthetic genetic circuits, it has proved challenging to obtain predictable design outcomes. In particular, context-dependence due to sharing a limited pool of cellular resources is a major factor that confounds modular composition of genetic modules. Here, we propose the use of a systems framework in which resource sharing among different subsystems is explicitly modeled through disturbance inputs and outputs. Within this system description, resource sharing results in undesired connectivity among subsystems, which is explicitly accounted for in design. Accordingly, we propose to use this system framework to co-design stable systems, with constant input, based on steady state specifications that each subsystem should satisfy. To this end, we provide sufficient conditions on the system parameters such that the output of each subsystem in the network remains in a small interval around a desired value, as well as an algorithmic procedure to compute the feasible region for these parameters. In general, this framework can be used to design subsystems to satisfy a specification, while explicitly accounting for context-dependence.