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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.


Dynamics for our biological memory device implementing a JK-Latch. In (a) dynamics of A, in (b) dynamics of B, in (c) dynamics of J, and in (d) dynamics of K
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Fig4: Dynamics for our biological memory device implementing a JK-Latch. In (a) dynamics of A, in (b) dynamics of B, in (c) dynamics of J, and in (d) dynamics of K

Mentions: The work principle of this circuit relies on the fact that there are two stable states and the behavior fluctuates as a flip-flop from one to another according to the external inputs. In the first state (or state A), protein A is expressed activating D, which is in charge of repressing B and C (see Fig. 3c). In the second state (or state B), protein B is expressed repressing A (see Fig. 3d). In this case, C and D remain inactivated. According to the specifications of this circuit, the system remains in its current state when no inputs are present. When K is present the system is set to the state A (i.e., no changes are observed if the system is already in that state, and a flip-flop is produced if the system is in the state B). On the other hand, the transcription factor J is the setter for the state B. A switch of state is always produced when the two inputs pulse simultaneously. In addition, our system has the property to oscillate when both inputs are continuously present. We can see this dynamics in Fig. 4 in which we show different input conditions during a simulation of 1,000 min.Fig. 4


Computational design of digital and memory biological devices.

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

Dynamics for our biological memory device implementing a JK-Latch. In (a) dynamics of A, in (b) dynamics of B, in (c) dynamics of J, and in (d) dynamics of K
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2553324&req=5

Fig4: Dynamics for our biological memory device implementing a JK-Latch. In (a) dynamics of A, in (b) dynamics of B, in (c) dynamics of J, and in (d) dynamics of K
Mentions: The work principle of this circuit relies on the fact that there are two stable states and the behavior fluctuates as a flip-flop from one to another according to the external inputs. In the first state (or state A), protein A is expressed activating D, which is in charge of repressing B and C (see Fig. 3c). In the second state (or state B), protein B is expressed repressing A (see Fig. 3d). In this case, C and D remain inactivated. According to the specifications of this circuit, the system remains in its current state when no inputs are present. When K is present the system is set to the state A (i.e., no changes are observed if the system is already in that state, and a flip-flop is produced if the system is in the state B). On the other hand, the transcription factor J is the setter for the state B. A switch of state is always produced when the two inputs pulse simultaneously. In addition, our system has the property to oscillate when both inputs are continuously present. We can see this dynamics in Fig. 4 in which we show different input conditions during a simulation of 1,000 min.Fig. 4

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.