Computational simulation of a gene regulatory network implementing an extendable synchronous single-input delay flip-flop

Abstract

We present a detailed and extendable design of the first synchronous single-input delay flip-flop implemented as a gene regulatory network in Escherichia coli (E. coli). The device, which we call the BioD, has one data input (transacting RNA), one clock input (far-red light) and an output that reports the state of the device using green fluorescent protein (GFP). The proposed design builds on Gardner's toggle switch, to provide a more sophisticated device that can be synchronized with other devices within the same cell, and which requires only one data input. We provide a mathematical model of the system and simulation results. The results show that the device behaves in line with desired functionality. Further, we discuss the constraints of the design, which pertain to ranges of parameter values. The BioD is extended via the addition of an update function and input and output interfaces. The result is the BioFSM, which constitutes a synchronous and modular finite state machine, which uses an update function to change its state, stored in the BioD. The BioFSM uses its input and output interfaces for inter-cellular communications. This opens the door to the design of a circular cellular automata (the BioCell), which is envisioned as a number of communicating E. coli colonies, each made of clones of one BioFSM. © 2012 Elsevier Ireland Ltd.