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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.


Stochastic simulations (Gillespie 1977) for the memory device implementing a JK-Latch. We have considered 100 molecules as 1 unit in terms of concentration. A is shown in gray and B in black. In (a) K is set to high at 50 min while J is always low starting with the state B, in (b) J is set to high at 50 min while K is low starting with the state A, in (c) J and K are set to high at 50 min for just 10 min starting with the state B, and in (d) J and K are set to high at 50 min starting with the state B
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Fig6: Stochastic simulations (Gillespie 1977) for the memory device implementing a JK-Latch. We have considered 100 molecules as 1 unit in terms of concentration. A is shown in gray and B in black. In (a) K is set to high at 50 min while J is always low starting with the state B, in (b) J is set to high at 50 min while K is low starting with the state A, in (c) J and K are set to high at 50 min for just 10 min starting with the state B, and in (d) J and K are set to high at 50 min starting with the state B

Mentions: Also, we have performed a stochastic simulation (Gillespie 1977) of this circuit to see its robustness under molecular noise (see Fig. 6). We have simulated several input conditions from different initial conditions. To perform such simulation we define a set of effective reactions involving the whole process of transcription and translation. We consider two possible reactions: protein synthesis and protein degradation, neglecting the fluctuations due to the mRNA dynamics. Hence, their fluxes are Hill functions of the transcription factors. We provide a MatLab file to perform this simulation as supporting information. We can see how the average behavior of the system is maintained as in Fig. 4. Further simulations could be performed, by detailing the reaction map and proposing typical parameter values to complete it, to obtain more accurate stochastic dynamics as the molecular noise can induce errors in the dynamics (Kepler and Elston 2001).Fig. 6


Computational design of digital and memory biological devices.

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

Stochastic simulations (Gillespie 1977) for the memory device implementing a JK-Latch. We have considered 100 molecules as 1 unit in terms of concentration. A is shown in gray and B in black. In (a) K is set to high at 50 min while J is always low starting with the state B, in (b) J is set to high at 50 min while K is low starting with the state A, in (c) J and K are set to high at 50 min for just 10 min starting with the state B, and in (d) J and K are set to high at 50 min starting with the state B
© Copyright Policy
Related In: Results  -  Collection

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

Fig6: Stochastic simulations (Gillespie 1977) for the memory device implementing a JK-Latch. We have considered 100 molecules as 1 unit in terms of concentration. A is shown in gray and B in black. In (a) K is set to high at 50 min while J is always low starting with the state B, in (b) J is set to high at 50 min while K is low starting with the state A, in (c) J and K are set to high at 50 min for just 10 min starting with the state B, and in (d) J and K are set to high at 50 min starting with the state B
Mentions: Also, we have performed a stochastic simulation (Gillespie 1977) of this circuit to see its robustness under molecular noise (see Fig. 6). We have simulated several input conditions from different initial conditions. To perform such simulation we define a set of effective reactions involving the whole process of transcription and translation. We consider two possible reactions: protein synthesis and protein degradation, neglecting the fluctuations due to the mRNA dynamics. Hence, their fluxes are Hill functions of the transcription factors. We provide a MatLab file to perform this simulation as supporting information. We can see how the average behavior of the system is maintained as in Fig. 4. Further simulations could be performed, by detailing the reaction map and proposing typical parameter values to complete it, to obtain more accurate stochastic dynamics as the molecular noise can induce errors in the dynamics (Kepler and Elston 2001).Fig. 6

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.