Synthesis of Genetic Clock with Combinational Biologic Circuits.

The potential of genetic clock lies in its role to triggering logic reaction for sequential biological circuits. In general, biochemical reaction of the biological system is extremely slow. However, a square wave generator used as a genetic clock the transient response should be fast enough to catch the reaction change between two logic levels. Therefore, the requirement for instantaneous changes in logic status is not likely to exist in biological systems. This paper presents a method of synthesizing a genetic clock generator based on the combination of a toggle switch with two biological logic gates. A dual repressor is used to connect the two fundamental biologic circuits. Analysis of the characteristic responses of this genetic clock with its relation to the key parameters is provided.

Synthesising gene clock with toggle switch and oscillator.

The usefulness of a genetic clock lies in its role to stimulate a sequence of logic reactions for sequential biological circuits. A clock signal is a periodic square wave, its amplitude alternates at a steady frequency between fixed minimal and maximal levels. Transition between the minimum and the maximum is instantaneous for an ideal square wave; however, the function is unrealisable in physical bio-systems. This research develops a new genetic clock generator based on a genetic oscillator, in which, a sine wave generator is adopted as a signal oscillator. It is shown that combination of a genetic oscillator with a toggle switch is able to generate clock signals forming an efficient way to generate a near square wave. In silico study confirms the proposed idea.

Synthesising periodic triggering signals with genetic oscillators.

The potential of the clock lies in its role of triggering logic reaction for sequential biological circuits. This research introduces an idea of designing a genetic clock generator by Fourier series based on the genetic oscillators. The authors generalise the design idea using a combination of fundamental sinusoidal signals. Since biochemical reaction of the biological system is extremely slow, however, transition between minimal and maximal levels is instantaneous for an ideal clock signal; it is thus not directly realisable in biological systems. That means it would be hard to directly synthesize a square wave generator for use as a genetic clock. They apply Fourier series to represent a square wave as a finite summation of sinusoidal waves generated by some genetic oscillators with different harmonic oscillating frequencies, in which the amplitude alternates at a constant frequency between the fixed minimal and maximal levels with the same duration of time.

Design of synthetic biological logic circuits based on evolutionary algorithm.

The construction of an artificial biological logic circuit using systematic strategy is recognised as one of the most important topics for the development of synthetic biology. In this study, a real-structured genetic algorithm (RSGA), which combines general advantages of the traditional real genetic algorithm with those of the structured genetic algorithm, is proposed to deal with the biological logic circuit design problem. A general model with the cis-regulatory input function and appropriate promoter activity functions is proposed to synthesise a wide variety of fundamental logic gates such as NOT, Buffer, AND, OR, NAND, NOR and XOR. The results obtained can be extended to synthesise advanced combinational and sequential logic circuits by topologically distinct connections. The resulting optimal design of these logic gates and circuits are established via the RSGA. The in silico computer-based modelling technology has been verified showing its great advantages in the purpose.