Rational design for functional topology and its applications in synthetic biology

SUN Zhi; YANG Ning; LOU Chunbo; TANG Chao; YANG Xiaojing

doi:10.12211/2096-8280.2023-003

您当前的位置：

首页 >

文章列表页 >

Rational design for functional topology and its applications in synthetic biology

Invited Review | 更新时间：2025-03-20

- Rational design for functional topology and its applications in synthetic biology
- Synthetic Biology Journal Vol. 4, Issue 3, Pages: 444-463(2023)
- 作者机构：
  
  1.北京大学定量生物学中心，北京大学-清华大学生命科学联合中心，北京大学前沿学科交叉研究院，北京大学，北京 100871
  2.中国科学院深圳先进技术研究院，细胞与基因线路设计中心，广东深圳 518000
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2023-003
  CLC： Q81
- Received：02 January 2023，
  
  Revised：2023-02-09，
  
  Published：30 June 2023
- 稿件说明：
移动端阅览
孙智，杨宁，娄春波，汤超，杨晓静. 功能拓扑的理性设计及其在合成生物学中的应用［J］. 合成生物学， 2023， 4（3）： 444-463

SUN Zhi， YANG Ning， LOU Chunbo， TANG Chao， YANG Xiaojing. Rational design for functional topology and its applications in synthetic biology［J］. Synthetic Biology Journal， 2023， 4（3）： 444-463
孙智，杨宁，娄春波，汤超，杨晓静. 功能拓扑的理性设计及其在合成生物学中的应用［J］. 合成生物学， 2023， 4（3）： 444-463 DOI： 10.12211/2096-8280.2023-003.

SUN Zhi， YANG Ning， LOU Chunbo， TANG Chao， YANG Xiaojing. Rational design for functional topology and its applications in synthetic biology［J］. Synthetic Biology Journal， 2023， 4（3）： 444-463 DOI： 10.12211/2096-8280.2023-003.

摘要

生物网络以超乎寻常的精度、可靠性和鲁棒性执行着各种各样复杂的功能。网络的拓扑结构、动力学性质与功能之间密切相关。如何定量刻画这种关系，找到复杂多样的生物网络的底层设计规律是系统生物学和合成生物学的巨大挑战。本文对功能拓扑的理性设计及其在合成生物学中的应用进行了综述。生物网络在统计性质上不同于随机网络，其结构呈现出模块化的趋势，本文首先总结了自然生物系统中出现的高频模块及其功能，回顾了最近系统生物学对于功能拓扑设计原理的探索，包括目前搜索功能拓扑的两种常用计算方法，同时对理论获得的典型功能拓扑进行了总结。继而总结了近年来实际合成生物学系统中功能拓扑的设计和构建，以基于转录调控的基因回路为主，按照其内部调控节点的数目，系统地介绍了不同拓扑结构被用来实现的具体功能及其典型实例。最后，介绍了近期自动化设计集成基因线路的发展、非转录多层次调控机制以及网络鲁棒性的设计原理，并简单探讨了对于复杂功能拓扑设计的机遇和挑战。

Abstract

Biological networks are capable of performing complex functions with accuracy

reliability

and robustness. In topology

the dynamic property and function of a network are closely related. How to depict this relationship quantitatively and discover design principles for complex and diverse biological networks are great challenges. In this review

we comment progress in this regard and its applications in synthetic biology. Biological networks are different statistically from random ones

which show a characteristic of modularization. There are recurrent network motifs linked to particular functions

such as temporally programed expression

reliable cell decisions

and robust biological oscillations

suggesting that despite the apparent complexity of cellular networks

there may only be a limited number of topological networks for executing particular biological functions robustly. Indeed

by enumerating all possible topological networks with two or three nodes

systems biology studies have shown that only a handful of topological network

s can perform a given function. Here

we first summarize the high-frequency modules and their functions in natural biological systems

review progress in systems biology to find design principles for functional topology

including two current methods (

enumeration and optimization) to search functional topology computationally

and highlight the typical functional topological networks that have been developed theoretically so far. Then

we focus on the functional topology that has been constructed and used in synthetic biology

such as genetic circuits developed based on transcriptional regulation. Organized by the number of nodes

we show typical examples and applications of different functional topological networks

including single-node positive/negative feedback loops

two-node positive/negative feedback loops

multi-node negative feedback/feedforward loops

and the combinational logic gates etc. Finally

we address frontiers in functional topology

including automated design of integrated gene circuits

other regulatory mechanisms beyond transcription

design of network robustness. We end by briefly discussing opportunities and challenges for designing complex functional topological networks.

关键词

Keywords

references

MILO R , SHEN-ORR S , ITZKOVITZ S , et al . Network motifs: simple building blocks of complex networks [J ] . Science , 2002 , 298 ( 5594 ): 824 - 827 .

JEONG H , TOMBOR B , ALBERT R , et al . The large-scale organization of metabolic networks [J ] . Nature , 2000 , 407 ( 6804 ): 651 - 654 .

SHEN-ORR S S , MILO R , MANGAN S , et al . Network motifs in the transcriptional regulation network of Escherichia coli [J ] . Nature Genetics , 2002 , 31 ( 1 ): 64 - 68 .

LIM W A , LEE C M , TANG C . Design principles of regulatory networks: searching for the molecular algorithms of the cell [J ] . Molecular Cell , 2013 , 49 ( 2 ): 202 - 212 .

ROSENFELD N , ELOWITZ M B , ALON U . Negative autoregulation speeds the response times of transcription networks [J ] . Journal of Molecular Biology , 2002 , 323 ( 5 ): 785 - 793 .

ISAACS F J , HASTY J , CANTOR C R , et al . Prediction and measurement of an autoregulatory genetic module [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2003 , 100 ( 13 ): 7714 - 7719 .

GUAN Y , CHEN X M , SHAO B , et al . Mitigating host burden of genetic circuits by engineering autonegatively regulated parts and improving functional prediction [J ] . ACS Synthetic Biology , 2022 , 11 ( 7 ): 2361 - 2371 .

ALON U . Network motifs: theory and experimental approaches [J ] . Nature Reviews Genetics , 2007 , 8 ( 6 ): 450 - 461 .

SNEPPEN K , KRISHNA S , SEMSEY S . Simplified models of biological networks [J ] . Annual Review of Biophysics , 2010 , 39 : 43 - 59 .

OPPENHEIM A B , KOBILER O , STAVANS J , et al . Switches in bacteriophage lambda development [J ] . Annual Review of Genetics , 2005 , 39 : 409 - 429 .

BECSKEI A , SERRANO L . Engineering stability in gene networks by autoregulation [J ] . Nature , 2000 , 405 ( 6786 ): 590 - 593 .

HSU C , SCHERRER S , BUETTI-DINH A , et al . Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution [J ] . Nature Communications , 2012 , 3 : 682 .

NIE Q , QIAO L X , QIU Y C , et al . Noise control and utility: from regulatory network to spatial patterning [J ] . Science China Mathematics , 2020 , 63 ( 3 ): 425 - 440 .

BOURKE ARNVIG K , PEDERSEN S , SNEPPEN K . Thermodynamics of heat-shock response [J ] . Physical Review Letters , 2000 , 84 ( 13 ): 3005 - 3008 .

KRISHNA S , JENSEN M H , SNEPPEN K . Minimal model of spiky oscillations in NF-κB signaling [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2006 , 103 ( 29 ): 10840 - 10845 .

HOELLER O , GONG D , WEINER O D . How to understand and outwit adaptation [J ] . Developmental Cell , 2014 , 28 ( 6 ): 607 - 616 .

MA W Z , LAI L H , OUYANG Q , et al . Robustness and modular design of the Drosophila segment polarity network [J ] . Molecular Systems Biology , 2006 , 2 : 70 .

MA W Z , TRUSINA A , EL-SAMAD H , et al . Defining network topologies that can achieve biochemical adaptation [J ] . Cell , 2009 , 138 ( 4 ): 760 - 773 .

BARKAI N , LEIBLER S . Robustness in simple biochemical networks [J ] . Nature , 1997 , 387 ( 6636 ): 913 - 917 .

STELLING J , GILLES E D , DOYLE F J . Robustness properties of circadian clock architectures [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2004 , 101 ( 36 ): 13210 - 13215 .

SHAH N A , SARKAR C A . Robust network topologies for generating switch-like cellular responses [J ] . PLoS Computational Biology , 2011 , 7 ( 6 ): e1002085 .

WAGNER A . Circuit topology and the evolution of robustness in two-gene circadian oscillators [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2005 , 102 ( 33 ): 11775 - 11780 .

CHAU A H , WALTER J M , GERARDIN J , et al . Designing synthetic regulatory networks capable of self-organizing cell polarization [J ] . Cell , 2012 , 151 ( 2 ): 320 - 332 .

ZHANG M Y , TANG C . Bi-functional biochemical networks [J ] . Physical Biology , 2018 , 16 ( 1 ): 016001 .

GAO Z M , CHEN S H , QIN S S , et al . Network motifs capable of decoding transcription factor dynamics [J ] . Scientific Reports , 2018 , 8 : 3594 .

QIAO L X , ZHAO W , TANG C , et al . Network topologies that can achieve dual function of adaptation and noise attenuation [J ] . Cell Systems , 2019 , 9 ( 3 ): 271 - 285.e7 .

QIAO L X , ZHANG Z B , ZHAO W , et al . Network design principle for robust oscillatory behaviors with respect to biological noise [J ] . eLife , 2022 , 11 : e76188 .

ELOWITZ M B , LEIBLER S . A synthetic oscillatory network of transcriptional regulators [J ] . Nature , 2000 , 403 ( 6767 ): 335 - 338 .

FRANÇOIS P , HAKIM V . Design of genetic networks with specified functions by evolution in silico [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2004 , 101 ( 2 ): 580 - 585 .

FRANÇOIS P , SIGGIA E D . A case study of evolutionary computation of biochemical adaptation [J ] . Physical Biology , 2008 , 5 ( 2 ): 026009 .

FRANÇOIS P , SIGGIA E D . Predicting embryonic patterning using mutual entropy fitness and in silico evolution [J ] . Development , 2010 , 137 ( 14 ): 2385 - 2395 .

LECUN Y , BENGIO Y , HINTON G . Deep learning [J ] . Nature , 2015 , 521 ( 7553 ): 436 - 444 .

SHEN J X , LIU F , TU Y H , et al . Finding gene network topologies for given biological function with recurrent neural network [J ] . Nature Communications , 2021 , 12 : 3125 .

CHEN F , LI C H . Inferring structural and dynamical properties of gene networks from data with deep learning [J ] . NAR Genomics and Bioinformatics , 2022 , 4 ( 3 ): lqac068 .

NEVOZHAY D , ADAMS R M , MURPHY K F , et al . Negative autoregulation linearizes the dose-response and suppresses the heterogeneity of gene expression [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2009 , 106 ( 13 ): 5123 - 5128 .

NEVOZHAY D , ZAL T , BALÁZSI G . Transferring a synthetic gene circuit from yeast to mammalian cells [J ] . Nature Communications , 2013 , 4 : 1451 .

GUINN M T , BALÁZSI G . Noise-reducing optogenetic negative-feedback gene circuits in human cells [J ] . Nucleic Acids Research , 2019 , 47 ( 14 ): 7703 - 7714 .

AJO-FRANKLIN C M , DRUBIN D A , ESKIN J A , et al . Rational design of memory in eukaryotic cells [J ] . Genes & Development , 2007 , 21 ( 18 ): 2271 - 2276 .

BURRILL D R , INNISS M C , BOYLE P M , et al . Synthetic memory circuits for tracking human cell fate [J ] . Genes & Development , 2012 , 26 ( 13 ): 1486 - 1497 .

LONGO D M , HOFFMANN A , TSIMRING L S , et al . Coherent activation of a synthetic mammalian gene network [J ] . Systems and Synthetic Biology , 2010 , 4 ( 1 ): 15 - 23 .

KRAMER B P , FUSSENEGGER M . Hysteresis in a synthetic mammalian gene network [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2005 , 102 ( 27 ): 9517 - 9522 .

CHEN D , ARKIN A P . Sequestration-based bistability enables tuning of the switching boundaries and design of a latch [J ] . Molecular Systems Biology , 2012 , 8 ( 1 ): 620 .

GARDNER T S , CANTOR C R , COLLINS J J . Construction of a genetic toggle switch in Escherichia coli [J ] . Nature , 2000 , 403 ( 6767 ): 339 - 342 .

KOBAYASHI H , KAERN M , ARAKI M , et al . Programmable cells: interfacing natural and engineered gene networks [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2004 , 101 ( 22 ): 8414 - 8419 .

CAMERON D E , COLLINS J J . Tunable protein degradation in bacteria [J ] . Nature Biotechnology , 2014 , 32 ( 12 ): 1276 - 1281 .

WU M , SU R Q , LI X H , et al . Engineering of regulated stochastic cell fate determination [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2013 , 110 ( 26 ): 10610 - 10615 .

KRAMER B P , VIRETTA A U , DAOUD-EL BABA M , et al . An engineered epigenetic transgene switch in mammalian cells [J ] . Nature Biotechnology , 2004 , 22 ( 7 ): 867 - 870 .

LEBAR T , BEZELJAK U , GOLOB A , et al . A bistable genetic switch based on designable DNA-binding domains [J ] . Nature Communications , 2014 , 5 : 5007 .

LI Y Q , JIANG Y , CHEN H , et al . Modular construction of mammalian gene circuits using TALE transcriptional repressors [J ] . Nature Chemical Biology , 2015 , 11 ( 3 ): 207 - 213 .

CHEN S B , ZHANG H Q , SHI H D , et al . Automated design of genetic toggle switches with predetermined bistability [J ] . ACS Synthetic Biology , 2012 , 1 ( 7 ): 284 - 290 .

STRICKER J , COOKSON S , BENNETT M R , et al . A fast, robust and tunable synthetic gene oscillator [J ] . Nature , 2008 , 456 ( 7221 ): 516 - 519 .

HUSSAIN F , GUPTA C , HIRNING A J , et al . Engineered temperature compensation in a synthetic genetic clock [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2014 , 111 ( 3 ): 972 - 977 .

MONDRAGÓN-PALOMINO O , DANINO T , SELIMKHANOV J , et al . Entrainment of a population of synthetic genetic oscillators [J ] . Science , 2011 , 333 ( 6047 ): 1315 - 1319 .

TIGGES M , MARQUEZ-LAGO T T , STELLING J , et al . A tunable synthetic mammalian oscillator [J ] . Nature , 2009 , 457 ( 7227 ): 309 - 312 .

TIGGES M , DÉNERVAUD N , GREBER D , et al . A synthetic low-frequency mammalian oscillator [J ] . Nucleic Acids Research , 2010 , 38 ( 8 ): 2702 - 2711 .

SUN Z , WEI W J , ZHANG M Y , et al . Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback [J ] . Nucleic Acids Research , 2022 , 50 ( 4 ): 2377 - 2386 .

POTVIN-TROTTIER L , LORD N D , VINNICOMBE G , et al . Synchronous long-term oscillations in a synthetic gene circuit [J ] . Nature , 2016 , 538 ( 7626 ): 514 - 517 .

LURO S , POTVIN-TROTTIER L , OKUMUS B , et al . Isolating live cells after high-throughput, long-term, time-lapse microscopy [J ] . Nature Methods , 2020 , 17 ( 1 ): 93 - 100 .

MANGAN S , ALON U . Structure and function of the feed-forward loop network motif [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2003 , 100 ( 21 ): 11980 - 11985 .

MANGAN S , ZASLAVER A , ALON U . The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks [J ] . Journal of Molecular Biology , 2003 , 334 ( 2 ): 197 - 204 .

KALIR S , MANGAN S , ALON U . A coherent feed-forward loop with a SUM input function prolongs flagella expression in Escherichia coli [J ] . Molecular Systems Biology , 2005 , 1 : 2005 .0006.

MANGAN S , ITZKOVITZ S , ZASLAVER A , et al . The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli [J ] . Journal of Molecular Biology , 2006 , 356 ( 5 ): 1073 - 1081 .

KAPLAN S , BREN A , DEKEL E , et al . The incoherent feed-forward loop can generate non-monotonic input functions for genes [J ] . Molecular Systems Biology , 2008 , 4 : 203 .

GOENTORO L , SHOVAL O , KIRSCHNER M W , et al . The incoherent feedforward loop can provide fold-change detection in gene regulation [J ] . Molecular Cell , 2009 , 36 ( 5 ): 894 - 899 .

BASU S , MEHREJA R , THIBERGE S , et al . Spatiotemporal control of gene expression with pulse-generating networks [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2004 , 101 ( 17 ): 6355 - 6360 .

BASU S , GERCHMAN Y , COLLINS C H , et al . A synthetic multicellular system for programmed pattern formation [J ] . Nature , 2005 , 434 ( 7037 ): 1130 - 1134 .

TABOR J J , SALIS H M , SIMPSON Z B , et al . A synthetic genetic edge detection program [J ] . Cell , 2009 , 137 ( 7 ): 1272 - 1281 .

GREBER D , FUSSENEGGER M . An engineered mammalian band-pass network [J ] . Nucleic Acids Research , 2010 , 38 ( 18 ): e174 .

ZONG Y Q , ZHANG H M , LYU C , et al . Insulated transcriptional elements enable precise design of genetic circuits [J ] . Nature Communications , 2017 , 8 : 52 .

GUET C C , ELOWITZ M B , HSING W , et al . Combinatorial synthesis of genetic networks [J ] . Science , 2002 , 296 ( 5572 ): 1466 - 1470 .

TAMSIR A , TABOR J J , VOIGT C A . Robust multicellular computing using genetically encoded NOR gates and chemical 'wires' [J ] . Nature , 2011 , 469 ( 7329 ): 212 - 215 .

STANTON B C , NIELSEN A A K , TAMSIR A , et al . Genomic mining of prokaryotic repressors for orthogonal logic gates [J ] . Nature Chemical Biology , 2014 , 10 ( 2 ): 99 - 105 .

LOU C B , LIU X L , NI M , et al . Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch [J ] . Molecular Systems Biology , 2010 , 6 : 350 .

ZHANG H Q , LIN M , SHI H D , et al . Programming a Pavlovian-like conditioning circuit in Escherichia coli [J ] . Nature Communications , 2014 , 5 : 3102 .

ANDREWS L B , NIELSEN A A K , VOIGT C A . Cellular checkpoint control using programmable sequential logic [J ] . Science , 2018 , 361 ( 6408 ): eaap8987 .

NIELSEN A A K , DER B S , SHIN J , et al . Genetic circuit design automation [J ] . Science , 2016 , 352 ( 6281 ): aac7341 .

SHIN J , ZHANG S Y , DER B S , et al . Programming Escherichia coli to function as a digital display [J ] . Molecular Systems Biology , 2020 , 16 ( 3 ): e9401 .

PARK Y , ESPAH BORUJENI A , GOROCHOWSKI T E , et al . Precision design of stable genetic circuits carried in highly-insulated E. coli genomic landing pads [J ] . Molecular Systems Biology , 2020 , 16 ( 8 ): e9584 .

TAKETANI M , ZHANG J B , ZHANG S Y , et al . Genetic circuit design automation for the gut resident species Bacteroides thetaiotaomicron [J ] . Nature Biotechnology , 2020 , 38 ( 8 ): 962 - 969 .

CHEN Y , ZHANG S Y , YOUNG E M , et al . Genetic circuit design automation for yeast [J ] . Nature Microbiology , 2020 , 5 ( 11 ): 1349 - 1360 .

RUBENS J R , SELVAGGIO G , LU T K . Synthetic mixed-signal computation in living cells [J ] . Nature Communications , 2016 , 7 : 11658 .

KIM T , WEINBERG B , WONG W , et al . Scalable recombinase-based gene expression cascades [J ] . Nature Communications , 2021 , 12 ( 1 ): 2711 .

WROBLEWSKA L , KITADA T , ENDO K , et al . Mammalian synthetic circuits with RNA binding proteins for RNA-only delivery [J ] . Nature Biotechnology , 2015 , 33 ( 8 ): 839 - 841 .

WAGNER T E , BECRAFT J R , BODNER K , et al . Small-molecule-based regulation of RNA-delivered circuits in mammalian cells [J ] . Nature Chemical Biology , 2018 , 14 ( 11 ): 1043 - 1050 .

HENNINGSEN J , SCHWARZ-SCHILLING M , LEIBL A , et al . Single cell characterization of a synthetic bacterial clock with a hybrid feedback loop containing dCas9-sgRNA [J ] . ACS Synthetic Biology , 2020 , 9 ( 12 ): 3377 - 3387 .

NIELSEN A A K , VOIGT C A . Multi-input CRISPR/Cas genetic circuits that interface host regulatory networks [J ] . Molecular Systems Biology , 2014 , 10 ( 11 ): 763 .

ANDERSON D A , VOIGT C A . Competitive dCas9 binding as a mechanism for transcriptional control [J ] . Molecular Systems Biology , 2021 , 17 ( 11 ): e10512 .

ZHANG S Y , VOIGT C A . Engineered dCas9 with reduced toxicity in bacteria: implications for genetic circuit design [J ] . Nucleic Acids Research , 2018 , 46 ( 20 ): 11115 - 11125 .

KUO J , YUAN R S , SÁNCHEZ C , et al . Toward a translationally independent RNA-based synthetic oscillator using deactivated CRISPR-Cas [J ] . Nucleic Acids Research , 2020 , 48 ( 14 ): 8165 - 8177 .

SANTOS-MORENO J , TASIUDI E , STELLING J , et al . Multistable and dynamic CRISPRi-based synthetic circuits [J ] . Nature Communications , 2020 , 11 : 2746 .

FERNANDEZ-RODRIGUEZ J , VOIGT C A . Post-translational control of genetic circuits using Potyvirus proteases [J ] . Nucleic Acids Research , 2016 , 44 ( 13 ): 6493 - 6502 .

GAO X J , CHONG L S , KIM M S , et al . Programmable protein circuits in living cells [J ] . Science , 2018 , 361 ( 6408 ): 1252 - 1258 .

CHEN Z B , LINTON J M , ZHU R H , et al . A synthetic protein-level neural network in mammalian cells [EB/OL ] . bioRxiv , 2022 [ 2022-12-31 ] . https://www.biorxiv.org/content/10.1101/2022.07.10.499405v1 https://www.biorxiv.org/content/10.1101/2022.07.10.499405v1 .

ZHU R H , DEL RIO-SALGADO J M , GARCIA-OJALVO J , et al . Synthetic multistability in mammalian cells [J ] . Science , 2022 , 375 ( 6578 ): eabg9765 .

MISHRA D , BEPLER T , TEAGUE B , et al . An engineered protein-phosphorylation toggle network with implications for endogenous network discovery [J ] . Science , 2021 , 373 ( 6550 ): eaav0780 .

JAYANTHI S , NILGIRIWALA K S , DEL VECCHIO D . Retroactivity controls the temporal dynamics of gene transcription [J ] . ACS Synthetic Biology , 2013 , 2 ( 8 ): 431 - 441 .

QIAN Y L , HUANG H H , JIMÉNEZ J I , et al . Resource competition shapes the response of genetic circuits [J ] . ACS Synthetic Biology , 2017 , 6 ( 7 ): 1263 - 1272 .

NILGIRIWALA K S , JIMÉNEZ J , RIVERA P M , et al . Synthetic tunable amplifying buffer circuit in E. coli [J ] . ACS Synthetic Biology , 2015 , 4 ( 5 ): 577 - 584 .

MISHRA D , RIVERA P M , LIN A , et al . A load driver device for engineering modularity in biological networks [J ] . Nature Biotechnology , 2014 , 32 ( 12 ): 1268 - 1275 .

JONES R D , QIAN Y L , ILIA K , et al . Robust and tunable signal processing in mammalian cells via engineered covalent modification cycles [J ] . Nature Communications , 2022 , 13 : 1720 .

HUANG H H , QIAN Y L , DEL VECCHIO D . A quasi-integral controller for adaptation of genetic modules to variable ribosome demand [J ] . Nature Communications , 2018 , 9 : 5415 .

JONES R D , QIAN Y L , SICILIANO V , et al . An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells [J ] . Nature Communications , 2020 , 11 ( 1 ): 5690 .

FREI T , CELLA F , TEDESCHI F , et al . Characterization and mitigation of gene expression burden in mammalian cells [J ] . Nature Communications , 2020 , 11 : 4641 .

HUANG H H , BELLATO M , QIAN Y L , et al . dCas9 regulator to neutralize competition in CRISPRi circuits [J ] . Nature Communications , 2021 , 12 : 1692 .

ZHANG R , LI J , MELENDEZ-ALVAREZ J , et al . Topology-dependent interference of synthetic gene circuit function by growth feedback [J ] . Nature Chemical Biology , 2020 , 16 ( 6 ): 695 - 701 .

TAN C , MARGUET P , YOU L C . Emergent bistability by a growth-modulating positive feedback circuit [J ] . Nature Chemical Biology , 2009 , 5 ( 11 ): 842 - 848 .

LEE J W , GYORGY A , CAMERON D E , et al . Creating single-copy genetic circuits [J ] . Molecular Cell , 2016 , 63 ( 2 ): 329 - 336 .

CERONI F , BOO A , FURINI S , et al . Burden-driven feedback control of gene expression [J ] . Nature Methods , 2018 , 15 ( 5 ): 387 - 393 .

BARAJAS C , HUANG H H , GIBSON J , et al . Feedforward growth rate control mitigates gene activation burden [J ] . Nature Communications , 2022 , 13 : 7054 .

SEGALL-SHAPIRO T H , SONTAG E D , VOIGT C A . Engineered promoters enable constant gene expression at any copy number in bacteria [J ] . Nature Biotechnology , 2018 , 36 ( 4 ): 352 - 358 .

BLERIS L , XIE Z , GLASS D , et al . Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template [J ] . Molecular Systems Biology , 2011 , 7 : 519 .

LILLACCI G , BENENSON Y , KHAMMASH M . Synthetic control systems for high performance gene expression in mammalian cells [J ] . Nucleic Acids Research , 2018 , 46 ( 18 ): 9855 - 9863 .

AOKI S K , LILLACCI G , GUPTA A , et al . A universal biomolecular integral feedback controller for robust perfect adaptation [J ] . Nature , 2019 , 570 ( 7762 ): 533 - 537 .

FREI T , CHANG C H , FILO M , et al . A genetic mammalian proportional-integral feedback control circuit for robust and precise gene regulation [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2022 , 119 ( 24 ): e2122132119 .

ROSENFELD N , YOUNG J W , ALON U , et al . Accurate prediction of gene feedback circuit behavior from component properties [J ] . Molecular Systems Biology , 2007 , 3 : 143 .

ROSENFELD N , YOUNG J W , ALON U , et al . Gene regulation at the single-cell level [J ] . Science , 2005 , 307 ( 5717 ): 1962 - 1965 .

SHOPERA T , HENSON W R , NG A , et al . Robust, tunable genetic memory from protein sequestration combined with positive feedback [J ] . Nucleic Acids Research , 2015 , 43 ( 18 ): 9086 - 9094 .

WU F Q , SU R Q , LAI Y C , et al . Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination [J ] . eLife , 2017 , 6 : e23702 .

SALIS H M , MIRSKY E A , VOIGT C A . Automated design of synthetic ribosome binding sites to control protein expression [J ] . Nature Biotechnology , 2009 , 27 ( 10 ): 946 - 950 .

SHI W J , MA W Z , XIONG L Y , et al . Adaptation with transcriptional regulation [J ] . Scientific Reports , 2017 , 7 : 42648 .

ALON U . An introduction to systems biology: design principles of biological circuits [M ] . Boca Raton, FL : Chapman & Hall/CRC , 2007 .

ZHANG H M , CHEN S B , SHI H D , et al . Measurements of gene expression at steady state improve the predictability of part assembly [J ] . ACS Synthetic Biology , 2016 , 5 ( 3 ): 269 - 273 .

GREEN A A , KIM J , MA D , et al . Complex cellular logic computation using ribocomputing devices [J ] . Nature , 2017 , 548 ( 7665 ): 117 - 121 .

KIM J , ZHOU Y , CARLSON P D , et al . De novo -designed translation-repressing riboregulators for multi-input cellular logic [J ] . Nature Chemical Biology , 2019 , 15 ( 12 ): 1173 - 1182 .

CHEN Y J , LIU P , NIELSEN A A K , et al . Characterization of 582 natural and synthetic terminators and quantification of their design constraints [J ] . Nature Methods , 2013 , 10 ( 7 ): 659 - 664 .

MEYER A J , SEGALL-SHAPIRO T H , GLASSEY E , et al . Escherichia coli "Marionette" strains with 12 highly optimized small-molecule sensors [J ] . Nature Chemical Biology , 2019 , 15 ( 2 ): 196 - 204 .

HOSSAIN A , LOPEZ E , HALPER S M , et al . Automated design of thousands of nonrepetitive parts for engineering stable genetic systems [J ] . Nature Biotechnology , 2020 , 38 ( 12 ): 1466 - 1475 .

LOU C B , STANTON B , CHEN Y J , et al . Ribozyme-based insulator parts buffer synthetic circuits from genetic context [J ] . Nature Biotechnology , 2012 , 30 ( 11 ): 1137 - 1142 .

GOROCHOWSKI T E , ESPAH BORUJENI A , PARK Y , et al . Genetic circuit characterization and debugging using RNA-seq [J ] . Molecular Systems Biology , 2017 , 13 ( 11 ): 952 .

ESPAH BORUJENI A , ZHANG J , DOOSTHOSSEINI H , et al . Genetic circuit characterization by inferring RNA polymerase movement and ribosome usage [J ] . Nature Communications , 2020 , 11 : 5001 .

FONTANARROSA P , DOOSTHOSSEINI H , BORUJENI A E , et al . Genetic circuit dynamics: hazard and glitch analysis [J ] . ACS Synthetic Biology , 2020 , 9 ( 9 ): 2324 - 2338 .

JONES T S , OLIVEIRA S M D , MYERS C J , et al . Genetic circuit design automation with Cello 2.0 [J ] . Nature Protocols , 2022 , 17 ( 4 ): 1097 - 1113 .

DEL VECCHIO D , NINFA A J , SONTAG E D . Modular cell biology: retroactivity and insulation [J ] . Molecular Systems Biology , 2008 , 4 : 161 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Design, optimization and application of synthetic carbon-negative phototrophic community

Synthetic biology-powered cell membrane-derived nanoparticles for precision theranostics

Synthetic biology-driven advances in artificial blood research

Related Author

SUN Zhi

YANG Ning

LOU Chunbo

TANG Chao

YANG Xiaojing

ZHENG Haotian

LI Chaofeng

LIU Liangxu

Related Institution

Center for Quantitative Biology， Peking-Tsinghua Center for Life Sciences，Academy for Advanced Interdisciplinary Studies， Peking University

Shenzhen Institutes of Advanced Technology， Chinese Academy of Sciences

State Key Laboratory of Microbial Metabolism， School of Life Science and Technology， Shanghai Jiaotong University

Zhangjiang Institute for Advanced Study， Shanghai Jiao Tong University

State Key Laboratory of Microbial Metabolism，School of Life Science and Technology，Shanghai Jiaotong University

⁰