A reconfigurable NAND/NOR genetic logic gate (original) (raw)
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Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology
Nature Communications, 2011
modular and orthogonal genetic logic gates are essential for building robust biologically based digital devices to customize cell signalling in synthetic biology. Here we constructed an orthogonal AnD gate in Escherichia coli using a novel hetero-regulation module from Pseudomonas syringae. The device comprises two co-activating genes hrpR and hrpS controlled by separate promoter inputs, and a σ 54 -dependent hrpL promoter driving the output. The hrpL promoter is activated only when both genes are expressed, generating digital-like AnD integration behaviour. The AnD gate is demonstrated to be modular by applying new regulated promoters to the inputs, and connecting the output to a noT gate module to produce a combinatorial nAnD gate. The circuits were assembled using a parts-based engineering approach of quantitative characterization, modelling, followed by construction and testing. The results show that new genetic logic devices can be engineered predictably from novel native orthogonal biological control elements using quantitatively in-context characterized parts.
Design principles of transcriptional logic circuits
Using a set of genetic logic gates (AND, OR and XOR), we constructed a binary full-adder. The optimality analysis of the full-adder showed that, based on the position of the regulation threshold, the system displays different optimal configurations for speed and accuracy under fixed metabolic cost. In addition, the analysis identified an optimal trade-off curve bounded by these two optimal configurations. Any configuration outside this optimal trade-off curve is sub-optimal in both speed and accuracy. This type of analysis represents a useful tool for synthetic biologists to engineer faster, more accurate and cheaper genes.
Journal of the American Chemical Society, 2004
A conceptually new logic gate based on DNA has been devised. Methoxybenzodeazaadenine (MD A), an artificial nucleobase which we recently developed for efficient hole transport through DNA, formed stable base pairs with T and C. However, a reasonable hole-transport efficiency was observed in the reaction for the duplex containing an MD A/T base pair, whereas the hole transport was strongly suppressed in the reaction using a duplex where the base opposite MD A was replaced by C. The influence of complementary pyrimidines on the efficiency of hole transport through MD A was quite contrary to the selectivity observed for hole transport through G. The orthogonality of the modulation of these hole-transport properties by complementary pyrimidine bases is promising for the design of a new molecular logic gate. The logic gate system was executed by hole transport through short DNA duplexes, which consisted of the "logic gate strand", containing hole-transporting nucleobases, and the "input strand", containing pyrimidines which modulate the hole-transport efficiency of logic bases. A logic gate strand containing multiple MD A bases in series provided the basis for a sharp AND logic action. On the other hand, for OR logic and combinational logic, conversion of Boolean expressions to standard sum-of-product (SOP) expressions was indispensable. Three logic gate strands were designed for OR logic according to each product term in the standard SOP expression of OR logic. The hole-transport efficiency observed for the mixed sample of logic gate strands exhibited an OR logic behavior. This approach is generally applicable to the design of other complicated combinational logic circuits such as the full-adder.
Engineering in the biological substrate: information processing in genetic circuits
Proceedings of the IEEE, 2000
We review the rapidly evolving efforts to analyze, model, simulate, and engineer genetic and biochemical information processing systems within living cells. We begin by showing that the fundamental elements of information processing in electronic and genetic systems are strikingly similar, and follow this theme through a review of efforts to create synthetic genetic circuits. In particular, we describe and review the "silicon mimetic" approach, where genetic circuits are engineered to mimic the functionality of semiconductor devices such as logic gates, latched circuits, and oscillators. This is followed with a review of the analysis, modeling, and simulation of natural and synthetic genetic circuits, which often proceed in a manner similar to that used for electronic systems. We conclude by presenting examples of naturally occurring genetic and biochemical systems that recently have been conceptualized in terms familiar to systems engineers. Our review of these newly forming fields of research demonstrates that the expertise and skills contained within electrical and computer engineering disciplines apply not only to design within biological systems, but also to the development of a deeper understanding of biological functionality. This review of these efforts points to the emergence of both engineering and basic science disciplines following parallel paths.
Noise-aided computation within a synthetic gene network through morphable and robust logic gates
Physical Review E, 2011
An important goal for synthetic biology is to build robust and tunable genetic regulatory networks that are capable of performing assigned operations, usually in the presence of noise. In this work, a synthetic gene network derived from the bacteriophage λ underpins a reconfigurable logic gate wherein we exploit noise and nonlinearity through the application of the logical stochastic resonance paradigm. This biological logic gate can emulate or "morph" the AND and OR operations through varying internal system parameters in a noisy background. Such genetic circuits can afford intriguing possibilities in the realization of engineered genetic networks in which the actual function of the gate can be changed after the network has been built, via an external control parameter. In this article, the full system characterization is reported, with the logic gate performance studied in the presence of external and internal noise. The robustness of the gate, to noise, is studied and illustrated through numerical simulations.
Another logical molecular NAND gate system
Proceedings of the Seventh International Conference on Microelectronics for Neural, Fuzzy and Bio-Inspired Systems
In this paper we implement a new logic NAND gate using standard operations on DNA strands as well as digestion by the restriction nuclease class II. This concept despite some difficulties looks in general more elegant and can be utilized with fluorescent probes. Some experimental results demonstrating implementation of a single logic NAND gate are provided. The derived logic gates are proposed to be implemented on DNA chips.
Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch
Molecular systems biology, 2010
Synopsis Design and synthesis of basic functional circuits are the fundamental tasks of synthetic biologists. Before it is possible to engineer higher-order genetic networks that can perform complex functions, a toolkit of basic devices must be developed. Among those devices, sequential logic circuits are expected to be the foundation of genetic information-processing systems.
Foundations for the design and implementation of synthetic genetic circuits
Nature Reviews Genetics, 2012
Synthetic gene circuits are designed to program new biological behaviour, dynamics and logic control. For all but the simplest synthetic phenotypes, this requires a structured approach to map the desired functionality to available molecular and cellular parts and processes. In other engineering disciplines, a formalized design process has greatly enhanced the scope and rate of success of projects. When engineering biological systems, a desired function must be achieved in a context that is incompletely known, is influenced by stochastic fluctuations and is capable of rich nonlinear interactions with the engineered circuitry. Here, we review progress in the provision and engineering of libraries of parts and devices, their composition into large systems and the emergence of a formal design process for synthetic biology.
Building blocks of a biochemical CPU based on DNA transcription logic
2004
In this paper we study the design of transcriptional logic based on quantitative models of cis-regulatory networks. Recent efforts in the area of synthetic biology have shown that logic gates can be implemented using the DNA transcriptional machinery of the cell. We show how to extend these previous results to the design of combinational and sequential circuits. The extension of our method to the design of sequential circuits is particularly attractive because they represent the most general class of circuits. As representative examples here we demonstrate the construction of a memory element and of a 1-bit ALU, two basic building blocks of a transcription-based biochemical CPU.