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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.


Hysteresis cycles for two different JK-Latches between the steady state of A and the pulsing amplitude of K for several constant values of J. In (a) computationally designed network (see Fig. 3). In (b) rationally designed network (see Fig. 2) with parameter optimization using our algorithm
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Fig5: Hysteresis cycles for two different JK-Latches between the steady state of A and the pulsing amplitude of K for several constant values of J. In (a) computationally designed network (see Fig. 3). In (b) rationally designed network (see Fig. 2) with parameter optimization using our algorithm

Mentions: Conditional systems show hysteresis effects. We have computed the steady state of A after a pulse of K for several constant values of J. In Fig. 5a, b we show the hysteresis diagrams for the rationally and computationally designed JK-Latches, respectively. At low levels of J, the system behaves as a memory device. However, for J = 0.5 the system is not appropriate as a memory device because it relaxes back to its previous state when the input disappears. In our computational design, when J = 0 the switch point occurs at K ≃ 0.7 μM. For higher values of J, this point increases and the system loses its ability to store information when we consider a constant J. For J close to 1 μM, the switching dynamics disappears. Similar results are obtained based on the rational design. In this case, for J = 0 the switch point is K ≃ 0.45 μM, and a constant leakage of J avoids reaching A = 1 μM (e.g., A = 0.25 μM for J = 0.5 μM) but still allows the memory function.Fig. 5


Computational design of digital and memory biological devices.

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

Hysteresis cycles for two different JK-Latches between the steady state of A and the pulsing amplitude of K for several constant values of J. In (a) computationally designed network (see Fig. 3). In (b) rationally designed network (see Fig. 2) with parameter optimization using our algorithm
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Related In: Results  -  Collection

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Fig5: Hysteresis cycles for two different JK-Latches between the steady state of A and the pulsing amplitude of K for several constant values of J. In (a) computationally designed network (see Fig. 3). In (b) rationally designed network (see Fig. 2) with parameter optimization using our algorithm
Mentions: Conditional systems show hysteresis effects. We have computed the steady state of A after a pulse of K for several constant values of J. In Fig. 5a, b we show the hysteresis diagrams for the rationally and computationally designed JK-Latches, respectively. At low levels of J, the system behaves as a memory device. However, for J = 0.5 the system is not appropriate as a memory device because it relaxes back to its previous state when the input disappears. In our computational design, when J = 0 the switch point occurs at K ≃ 0.7 μM. For higher values of J, this point increases and the system loses its ability to store information when we consider a constant J. For J close to 1 μM, the switching dynamics disappears. Similar results are obtained based on the rational design. In this case, for J = 0 the switch point is K ≃ 0.45 μM, and a constant leakage of J avoids reaching A = 1 μM (e.g., A = 0.25 μM for J = 0.5 μM) but still allows the memory function.Fig. 5

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.