Synthesizing a novel genetic sequential logic circuit: a push‐on push‐off switch

Lou, Chunbo; Liu, Xili; Ni, Ming; Huang, Yiqi; Huang, Qiushi; Huang, Longwen; Jiang, Lingli; Lü, Dan; Wang, Mingcong; Liu, Chang; Chen, Daizhuo; Wang, Hongli; Chen, Xiaoyue; Yang, Le; Ma, Haisu; Chen, Jianguo; Ouyang, Qi

doi:10.1038/msb.2010.2

Cited by 124 publications

(125 citation statements)

References 31 publications

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“…Living organisms elegantly manage transfer across their boundaries. Engineered bacteria have been used to implement collective behaviours, although the programming of living systems for such tasks remains challenging [40][41][42][43][44] .…”

Section: Resultsmentioning

confidence: 99%

Microscopic agents programmed by DNA circuits

Gines¹,

Zadorin²,

Galas³

et al. 2017

Nature Nanotech

125

148

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Section: Resultsmentioning

confidence: 99%

Microscopic agents programmed by DNA circuits

Gines¹,

Zadorin²,

Galas³

et al. 2017

Nature Nanotech

125

148

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“…We believe that whole-cell models will ultimately aid synthetic biologists in understanding and describing why synthetic circuits do not behave in vivo as expected from the predictions of isolated computational models. 10,39 This, in turn, should lead to models that can more accurately predict and thus enable the rational design of synthetic circuits. We intend this work to be taken as a preliminary investigation into the use of whole-cell models within synthetic biology.…”

Section: Discussionmentioning

confidence: 99%

Towards a whole-cell modeling approach for synthetic biology

Purcell

Jain

Karr

et al. 2013

Chaos: An Interdisciplinary Journal of Nonlinear Science

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Despite rapid advances over the last decade, synthetic biology lacks the predictive tools needed to enable rational design. Unlike established engineering disciplines, the engineering of synthetic gene circuits still relies heavily on experimental trial-and-error, a time-consuming and inefficient process that slows down the biological design cycle. This reliance on experimental tuning is because current modeling approaches are unable to make reliable predictions about the in vivo behavior of synthetic circuits. A major reason for this lack of predictability is that current models view circuits in isolation, ignoring the vast number of complex cellular processes that impinge on the dynamics of the synthetic circuit and vice versa. To address this problem, we present a modeling approach for the design of synthetic circuits in the context of cellular networks. Using the recently published whole-cell model of Mycoplasma genitalium, we examined the effect of adding genes into the host genome. We also investigated how codon usage correlates with gene expression and find agreement with existing experimental results. Finally, we successfully implemented a synthetic Goodwin oscillator in the whole-cell model. We provide an updated software framework for the whole-cell model that lays the foundation for the integration of wholecell models with synthetic gene circuit models. This software framework is made freely available to the community to enable future extensions. We envision that this approach will be critical to transforming the field of synthetic biology into a rational and predictive engineering discipline. Synthetic biology aims to engineer synthetic genetic circuits to endow cells and organisms with the ability to address new applications, including the production of drugs and industrial products, the design of new therapeutics for human diseases, and the study of basic biological processes. Despite significant advances in the field over the last decade, the synthetic biology design cycle has been hampered by the lack of predictive models. In contrast, more established engineering disciplines, such as civil and electrical engineering can rely on rational design by using models that can capture the behavior of real-world systems with a high degree of accuracy. This is currently not the case for synthetic biology, as models are generally only able to make qualitative predictions about system behavior. As a result, producing a functional engineered biological system usually requires extensive manual tuning by trial-and-error, a timeconsuming process that significantly slows the biological design process. The lack of predictive power in current models is partly because these models account for only the synthetic circuits themselves, but not other ongoing processes in the cells in which they reside. However, the complex dynamics of synthetic circuits may affect the host cell and vice versa, leading to divergence between current models and experimental results. Recently, a whole-cell model of a small and simple bacteri...

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“…The genetic switches based on transcription factors utilize diverse mechanisms to achieve their functionalities, which include: (1) the conformational change of transcription factors according to the environmental signals (Zhang et al, 2009), (2) translocation of transcriptional regulators (Buchler and Cross, 2009;Ghim and Almaas, 2009), (3) accession or depletion of small molecules (Sprengel and Hasan, 2007), and (4) response to several special signals, such as light, pH and redox potential (Pomposiello and Demple, 2001;Georgiou, 2002;Levskaya et al, 2009;Paulsen and Carroll, 2009;Tietze et al, 2009). More sophisticated genetic switches have also been engineered including bistable switches (Kim et al, 2006) and memory push-on push-off switches (Lou et al, 2010).…”

Section: Genetic Switchesmentioning

confidence: 99%

Synthetic circuits, devices and modules

Zhao

Jiang

2010

Protein Cell

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The aim of synthetic biology is to design artificial biological systems for novel applications. From an engineering perspective, construction of biological systems of defined functionality in a hierarchical way is fundamental to this emerging field. Here, we highlight some current advances on design of several basic building blocks in synthetic biology including the artificial gene control elements, synthetic circuits and their assemblies into devices and modules. Such engineered basic building blocks largely expand the synthetic toolbox and contribute to our understanding of the underlying design principles of living cells.

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Synthesizing a novel genetic sequential logic circuit: a push‐on push‐off switch

Cited by 124 publications

References 31 publications

Microscopic agents programmed by DNA circuits

Microscopic agents programmed by DNA circuits

Towards a whole-cell modeling approach for synthetic biology

Synthetic circuits, devices and modules

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