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A formalized design process for bacterial consortia that perform logic computing.

Ji W, Shi H, Zhang H, Sun R, Xi J, Wen D, Feng J, Chen Y, Qin X, Ma Y, Luo W, Deng L, Lin H, Yu R, Ouyang Q - PLoS ONE (2013)

Bottom Line: Despite of all its benefits, however, there are still problems remaining for large-scaled multicellular gene circuits, for example, how to reliably design and distribute the circuits in microbial consortia with limited number of well-behaved genetic modules and wiring quorum-sensing molecules.The construction and characterization of logic operators is independent of "wiring" and provides predictive information for fine-tuning.This formalized design process provides guidance for the design of microbial consortia that perform distributed biological computation.

View Article: PubMed Central - PubMed

Affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing, China.

ABSTRACT
The concept of microbial consortia is of great attractiveness in synthetic biology. Despite of all its benefits, however, there are still problems remaining for large-scaled multicellular gene circuits, for example, how to reliably design and distribute the circuits in microbial consortia with limited number of well-behaved genetic modules and wiring quorum-sensing molecules. To manage such problem, here we propose a formalized design process: (i) determine the basic logic units (AND, OR and NOT gates) based on mathematical and biological considerations; (ii) establish rules to search and distribute simplest logic design; (iii) assemble assigned basic logic units in each logic operating cell; and (iv) fine-tune the circuiting interface between logic operators. We in silico analyzed gene circuits with inputs ranging from two to four, comparing our method with the pre-existing ones. Results showed that this formalized design process is more feasible concerning numbers of cells required. Furthermore, as a proof of principle, an Escherichia coli consortium that performs XOR function, a typical complex computing operation, was designed. The construction and characterization of logic operators is independent of "wiring" and provides predictive information for fine-tuning. This formalized design process provides guidance for the design of microbial consortia that perform distributed biological computation.

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Work flow for the formalized design process and in silico analysis of different approaches in multicellular logic circuits.(A). Schematic view of the work flow for formalized design process. (B). Number of permissible 2-input 1-output Boolean functions versus the number of cells required for their implementation. Each bar represents number of functions that can be implemented within a certain number of cells. Different colors denote different approaches: orange for Standard NOR/NAND, blue for Modular Cells, and gray for our approach of combinational design. (C). Number of permissible 2-input 1-output Boolean functions versus the number of chemical wires required for their implementation. (D) and (E) show the results for 3-input 1-output Boolean functions.
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pone-0057482-g001: Work flow for the formalized design process and in silico analysis of different approaches in multicellular logic circuits.(A). Schematic view of the work flow for formalized design process. (B). Number of permissible 2-input 1-output Boolean functions versus the number of cells required for their implementation. Each bar represents number of functions that can be implemented within a certain number of cells. Different colors denote different approaches: orange for Standard NOR/NAND, blue for Modular Cells, and gray for our approach of combinational design. (C). Number of permissible 2-input 1-output Boolean functions versus the number of chemical wires required for their implementation. (D) and (E) show the results for 3-input 1-output Boolean functions.

Mentions: In this work, we explore the possibility of a formalized design process to balance the trade-off between standardization of logic operators and wiring efficiency in engineered microbial consortia. In this process [Fig. 1(A)], AND, OR and NOT gates are chosen as the basic logic units and are combined to express desired computing operation as simplest logic. The simplest logic is distributed into separated logic operating cells according to carefully established rules. Logic operators (logic operating cells) were constructed and tested independently, and then combined to create a complete logic circuit though fine-tuning circuiting interface. As proof of principle, an Escherichia coli consortium that performs XOR gate operation, the operation usually considered as difficult to implement in synthetic biology, was designed and implemented.


A formalized design process for bacterial consortia that perform logic computing.

Ji W, Shi H, Zhang H, Sun R, Xi J, Wen D, Feng J, Chen Y, Qin X, Ma Y, Luo W, Deng L, Lin H, Yu R, Ouyang Q - PLoS ONE (2013)

Work flow for the formalized design process and in silico analysis of different approaches in multicellular logic circuits.(A). Schematic view of the work flow for formalized design process. (B). Number of permissible 2-input 1-output Boolean functions versus the number of cells required for their implementation. Each bar represents number of functions that can be implemented within a certain number of cells. Different colors denote different approaches: orange for Standard NOR/NAND, blue for Modular Cells, and gray for our approach of combinational design. (C). Number of permissible 2-input 1-output Boolean functions versus the number of chemical wires required for their implementation. (D) and (E) show the results for 3-input 1-output Boolean functions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585339&req=5

pone-0057482-g001: Work flow for the formalized design process and in silico analysis of different approaches in multicellular logic circuits.(A). Schematic view of the work flow for formalized design process. (B). Number of permissible 2-input 1-output Boolean functions versus the number of cells required for their implementation. Each bar represents number of functions that can be implemented within a certain number of cells. Different colors denote different approaches: orange for Standard NOR/NAND, blue for Modular Cells, and gray for our approach of combinational design. (C). Number of permissible 2-input 1-output Boolean functions versus the number of chemical wires required for their implementation. (D) and (E) show the results for 3-input 1-output Boolean functions.
Mentions: In this work, we explore the possibility of a formalized design process to balance the trade-off between standardization of logic operators and wiring efficiency in engineered microbial consortia. In this process [Fig. 1(A)], AND, OR and NOT gates are chosen as the basic logic units and are combined to express desired computing operation as simplest logic. The simplest logic is distributed into separated logic operating cells according to carefully established rules. Logic operators (logic operating cells) were constructed and tested independently, and then combined to create a complete logic circuit though fine-tuning circuiting interface. As proof of principle, an Escherichia coli consortium that performs XOR gate operation, the operation usually considered as difficult to implement in synthetic biology, was designed and implemented.

Bottom Line: Despite of all its benefits, however, there are still problems remaining for large-scaled multicellular gene circuits, for example, how to reliably design and distribute the circuits in microbial consortia with limited number of well-behaved genetic modules and wiring quorum-sensing molecules.The construction and characterization of logic operators is independent of "wiring" and provides predictive information for fine-tuning.This formalized design process provides guidance for the design of microbial consortia that perform distributed biological computation.

View Article: PubMed Central - PubMed

Affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing, China.

ABSTRACT
The concept of microbial consortia is of great attractiveness in synthetic biology. Despite of all its benefits, however, there are still problems remaining for large-scaled multicellular gene circuits, for example, how to reliably design and distribute the circuits in microbial consortia with limited number of well-behaved genetic modules and wiring quorum-sensing molecules. To manage such problem, here we propose a formalized design process: (i) determine the basic logic units (AND, OR and NOT gates) based on mathematical and biological considerations; (ii) establish rules to search and distribute simplest logic design; (iii) assemble assigned basic logic units in each logic operating cell; and (iv) fine-tune the circuiting interface between logic operators. We in silico analyzed gene circuits with inputs ranging from two to four, comparing our method with the pre-existing ones. Results showed that this formalized design process is more feasible concerning numbers of cells required. Furthermore, as a proof of principle, an Escherichia coli consortium that performs XOR function, a typical complex computing operation, was designed. The construction and characterization of logic operators is independent of "wiring" and provides predictive information for fine-tuning. This formalized design process provides guidance for the design of microbial consortia that perform distributed biological computation.

Show MeSH
Related in: MedlinePlus