Develop reusable and combinable designs for transcriptional logic gates

Abstract One limit on developing complex synthetic gene circuits is the lack of basic components such as transcriptional logic gates that can process combinatorial inputs. Here, we propose a strategy to construct such components based on reusable designs and convergent reengineering of well‐studied...

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Main Authors: Jian Zhan, Bo Ding, Rui Ma, Xiaoyu Ma, Xiaofeng Su, Yun Zhao, Ziqing Liu, Jiarui Wu, Haiyan Liu
Format: Article
Language:English
Published: Springer Nature 2010-07-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/msb.2010.42
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author Jian Zhan
Bo Ding
Rui Ma
Xiaoyu Ma
Xiaofeng Su
Yun Zhao
Ziqing Liu
Jiarui Wu
Haiyan Liu
author_facet Jian Zhan
Bo Ding
Rui Ma
Xiaoyu Ma
Xiaofeng Su
Yun Zhao
Ziqing Liu
Jiarui Wu
Haiyan Liu
author_sort Jian Zhan
collection DOAJ
description Abstract One limit on developing complex synthetic gene circuits is the lack of basic components such as transcriptional logic gates that can process combinatorial inputs. Here, we propose a strategy to construct such components based on reusable designs and convergent reengineering of well‐studied natural systems. We demonstrated the strategy using variants of the transcription factor (TF) LacI and operator Olac that form specifically interacting pairs. Guided by a mathematical model derived from existing quantitative knowledge, rational designs of transcriptional NAND, NOR and NOT gates have been realized. The NAND gates have been designed based on direct protein–protein interactions in coupling with DNA looping. We demonstrated that the designs are reusable: a multiplex of logic devices can be readily created using the same designs but different combinations of sequence variants. The designed logic gates are combinable to form compound circuits: a demonstration logic circuit containing all three types of designed logic gates has been synthesized, and the circuit truthfully reproduces the pre‐designed input–output logic relations.
format Article
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institution Kabale University
issn 1744-4292
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publishDate 2010-07-01
publisher Springer Nature
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series Molecular Systems Biology
spelling doaj-art-d64b660607704735aa36fa26d87f080f2025-08-24T11:59:50ZengSpringer NatureMolecular Systems Biology1744-42922010-07-01611710.1038/msb.2010.42Develop reusable and combinable designs for transcriptional logic gatesJian Zhan0Bo Ding1Rui Ma2Xiaoyu Ma3Xiaofeng Su4Yun Zhao5Ziqing Liu6Jiarui Wu7Haiyan Liu8School of Life Sciences, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of ChinaHefei National Laboratory of Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of ChinaAbstract One limit on developing complex synthetic gene circuits is the lack of basic components such as transcriptional logic gates that can process combinatorial inputs. Here, we propose a strategy to construct such components based on reusable designs and convergent reengineering of well‐studied natural systems. We demonstrated the strategy using variants of the transcription factor (TF) LacI and operator Olac that form specifically interacting pairs. Guided by a mathematical model derived from existing quantitative knowledge, rational designs of transcriptional NAND, NOR and NOT gates have been realized. The NAND gates have been designed based on direct protein–protein interactions in coupling with DNA looping. We demonstrated that the designs are reusable: a multiplex of logic devices can be readily created using the same designs but different combinations of sequence variants. The designed logic gates are combinable to form compound circuits: a demonstration logic circuit containing all three types of designed logic gates has been synthesized, and the circuit truthfully reproduces the pre‐designed input–output logic relations.https://doi.org/10.1038/msb.2010.42combinabilitymathematical modelreusable designstranscriptional logic gates
spellingShingle Jian Zhan
Bo Ding
Rui Ma
Xiaoyu Ma
Xiaofeng Su
Yun Zhao
Ziqing Liu
Jiarui Wu
Haiyan Liu
Develop reusable and combinable designs for transcriptional logic gates
Molecular Systems Biology
combinability
mathematical model
reusable designs
transcriptional logic gates
title Develop reusable and combinable designs for transcriptional logic gates
title_full Develop reusable and combinable designs for transcriptional logic gates
title_fullStr Develop reusable and combinable designs for transcriptional logic gates
title_full_unstemmed Develop reusable and combinable designs for transcriptional logic gates
title_short Develop reusable and combinable designs for transcriptional logic gates
title_sort develop reusable and combinable designs for transcriptional logic gates
topic combinability
mathematical model
reusable designs
transcriptional logic gates
url https://doi.org/10.1038/msb.2010.42
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