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Computational design of digital and memory biological devices.

Rodrigo G, Jaramillo A - Syst Synth Biol (2008)

Bottom Line: Summary.We show how to use an automated procedure to design logic and sequential transcription circuits.This methodology will allow advancing the rational design of biological devices to more complex systems, and we propose the first design of a biological JK-latch memory device.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Biologia Molecular y Celular de Plantas, CSIC-Universidad Politecnica de Valencia, Valencia, Spain.

ABSTRACT
The use of combinatorial optimization techniques with computational design allows the development of automated methods to design biological systems. Automatic design integrates design principles in an unsupervised algorithm to sample a larger region of the biological network space, at the topology and parameter levels. The design of novel synthetic transcriptional networks with targeted behaviors will be key to understand the design principles underlying biological networks. In this work, we evolve transcriptional networks towards a targeted dynamics, by using a library of promoters and coding sequences, to design a complex biological memory device. The designed sequential transcription network implements a JK-Latch, which is fully predictable and richer than other memory devices. Furthermore, we present designs of transcriptional devices behaving as logic gates, and we show how to create digital behavior from analog promoters. Our procedure allows us to propose a scenario for the evolution of multi-functional genetic networks. In addition, we discuss the decomposability of regulatory networks in terms of genetic modules to develop a given cellular function. Summary. We show how to use an automated procedure to design logic and sequential transcription circuits. This methodology will allow advancing the rational design of biological devices to more complex systems, and we propose the first design of a biological JK-latch memory device.

No MeSH data available.


(a) Electronic implementation of a JK-Latch which is a sequential circuit. (b) Rational design of a biological memory device implementing a JK-Latch. The parameters and corresponding SBML file with the model can be found in the supplementary material
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Fig2: (a) Electronic implementation of a JK-Latch which is a sequential circuit. (b) Rational design of a biological memory device implementing a JK-Latch. The parameters and corresponding SBML file with the model can be found in the supplementary material

Mentions: We have designed two biological implementations of JK-Latches using transcription factors. The first one is guided by the electronic implementation (see Fig. 2a), where we have used as logic gates promoters with combinatorial regulation (see Fig. 2b). This rational approach is applied to engineer a JK-Latch by implementing on a RS-Latch two positive feedbacks from the outputs of the system (A and B). In that case, like in the electronic design, these feedbacks are integrated in two synergistically activated promoters. Unfortunately, it is not always possible to perform such rational designs, and in this article we aim to show a new technique to create alternative designs. As described in the previous section, we propose to use an unsupervised computational design technique. We have imposed the desired specifications (as shown in Fig. 3a) to design a novel circuit (see Fig. 3b) that has no resemblance to the previous rational design (see Fig. 2b). We have constructed by adding the eight scores constructed by using the four possible entries of the truth table shown in Fig. 3a for each of the two possible initial conditions (A = 1, B = 0 μM and A = 0, B = 1 μM). We provide as supporting information the corresponding SBML (Hucka et al. 2003) file containing the parameter values of the designed circuit. Our design was obtained by an in silico evolution optimizing both the topology and parameters of the network, without relying on an analogy between biology and electronics.Fig. 2


Computational design of digital and memory biological devices.

Rodrigo G, Jaramillo A - Syst Synth Biol (2008)

(a) Electronic implementation of a JK-Latch which is a sequential circuit. (b) Rational design of a biological memory device implementing a JK-Latch. The parameters and corresponding SBML file with the model can be found in the supplementary material
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553324&req=5

Fig2: (a) Electronic implementation of a JK-Latch which is a sequential circuit. (b) Rational design of a biological memory device implementing a JK-Latch. The parameters and corresponding SBML file with the model can be found in the supplementary material
Mentions: We have designed two biological implementations of JK-Latches using transcription factors. The first one is guided by the electronic implementation (see Fig. 2a), where we have used as logic gates promoters with combinatorial regulation (see Fig. 2b). This rational approach is applied to engineer a JK-Latch by implementing on a RS-Latch two positive feedbacks from the outputs of the system (A and B). In that case, like in the electronic design, these feedbacks are integrated in two synergistically activated promoters. Unfortunately, it is not always possible to perform such rational designs, and in this article we aim to show a new technique to create alternative designs. As described in the previous section, we propose to use an unsupervised computational design technique. We have imposed the desired specifications (as shown in Fig. 3a) to design a novel circuit (see Fig. 3b) that has no resemblance to the previous rational design (see Fig. 2b). We have constructed by adding the eight scores constructed by using the four possible entries of the truth table shown in Fig. 3a for each of the two possible initial conditions (A = 1, B = 0 μM and A = 0, B = 1 μM). We provide as supporting information the corresponding SBML (Hucka et al. 2003) file containing the parameter values of the designed circuit. Our design was obtained by an in silico evolution optimizing both the topology and parameters of the network, without relying on an analogy between biology and electronics.Fig. 2

Bottom Line: Summary.We show how to use an automated procedure to design logic and sequential transcription circuits.This methodology will allow advancing the rational design of biological devices to more complex systems, and we propose the first design of a biological JK-latch memory device.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Biologia Molecular y Celular de Plantas, CSIC-Universidad Politecnica de Valencia, Valencia, Spain.

ABSTRACT
The use of combinatorial optimization techniques with computational design allows the development of automated methods to design biological systems. Automatic design integrates design principles in an unsupervised algorithm to sample a larger region of the biological network space, at the topology and parameter levels. The design of novel synthetic transcriptional networks with targeted behaviors will be key to understand the design principles underlying biological networks. In this work, we evolve transcriptional networks towards a targeted dynamics, by using a library of promoters and coding sequences, to design a complex biological memory device. The designed sequential transcription network implements a JK-Latch, which is fully predictable and richer than other memory devices. Furthermore, we present designs of transcriptional devices behaving as logic gates, and we show how to create digital behavior from analog promoters. Our procedure allows us to propose a scenario for the evolution of multi-functional genetic networks. In addition, we discuss the decomposability of regulatory networks in terms of genetic modules to develop a given cellular function. Summary. We show how to use an automated procedure to design logic and sequential transcription circuits. This methodology will allow advancing the rational design of biological devices to more complex systems, and we propose the first design of a biological JK-latch memory device.

No MeSH data available.