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Tuning response curves for synthetic biology. ​

文献信息 ​

DOI10.1021/sb4000564
PMID23905721
期刊ACS synthetic biology
影响因子3.9
JCR 分区Q1
发表年份2013
被引次数63
关键词合成生物学, 响应曲线, 系统设计, 调节水平
文献类型Journal Article
ISSN2161-5063
页码547-67
期号2(10)
作者Jordan Ang, Edouard Harris, Brendan J Hussey, Richard Kil, David R McMillen

一句话小结 ​

本研究探讨了合成生物学中系统响应速率调节的关键性问题，提出了一种数学公式来描述生物响应曲线并定义了多种调节方式。通过对相关实验文献的综述，研究为更好地理解和设计多组件生物系统的动态和稳态特性提供了重要理论基础。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

合成生物学 · 响应曲线 · 系统设计 · 调节水平

摘要 ​

合成生物学可以被视为在生物系统的背景下建立、规范和发展一种工程学科的努力。调节单个组件属性的能力是所有工程领域系统设计过程中的核心内容，合成生物学也不例外。已经开发出大量且日益增长的方法来调节细胞系统的响应，在此我们特别关注系统响应速率调节的问题：在一个输入影响输出变化速率的系统中，如何通过实验改变响应曲线的形状？这影响了系统的动态特性以及其稳态特性，而这两者在合成生物学中设计系统时尤其重要，特别是对于多组件系统。我们首先回顾一种数学公式，该公式捕捉了广泛的生物响应曲线，并利用此公式定义了一套标准的调节种类：垂直位移、水平方向缩放等。接着，我们对实验文献进行了综述，将结果分类到我们定义的类别中，并按调控层次进行组织：转录后、转录后和翻译后。

英文摘要 ​

Synthetic biology may be viewed as an effort to establish, formalize, and develop an engineering discipline in the context of biological systems. The ability to tune the properties of individual components is central to the process of system design in all fields of engineering, and synthetic biology is no exception. A large and growing number of approaches have been developed for tuning the responses of cellular systems, and here we address specifically the issue of tuning the rate of response of a system: given a system where an input affects the rate of change of an output, how can the shape of the response curve be altered experimentally? This affects a system's dynamics as well as its steady-state properties, both of which are critical in the design of systems in synthetic biology, particularly those with multiple components. We begin by reviewing a mathematical formulation that captures a broad class of biological response curves and use this to define a standard set of varieties of tuning: vertical shifting, horizontal scaling, and the like. We then survey the experimental literature, classifying the results into our defined categories, and organizing them by regulatory level: transcriptional, post-transcriptional, and post-translational.

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主要研究问题 ​

  1. 在合成生物学中，如何具体选择和应用不同的调节机制来优化响应曲线？
  2. 针对不同的细胞系统，调节响应曲线的实验方法有哪些具体案例和成功经验？
  3. 如何评估和比较不同调节策略对合成生物学系统动态特性的影响？
  4. 在合成生物学中，响应曲线的调节对多组分系统的设计有何特别的挑战和机遇？
  5. 除了数学模型，是否还有其他方法可以有效描述和预测生物响应曲线的变化？

核心洞察 ​

研究背景和目的 ​

合成生物学旨在建立一种生物系统的工程学科，调节生物系统的响应曲线是实现这一目标的关键。本文探讨了如何通过实验手段调节细胞系统的响应速率，尤其是输入如何影响输出的变化速率。研究的目的是系统性地审视和分类现有的调节方法，并为合成生物学中的系统设计提供理论基础。

主要方法/材料/实验设计 ​

本研究首先引入了一种数学模型，用于描述生物响应曲线的广泛类别，随后定义了多种调节方式，包括垂直位移、水平缩放等。文献综述部分将实验结果按调节水平（转录后、转录后和翻译后）分类。

Mermaid diagram

关键结果和发现 ​

  1. 调节类型：

    • 垂直缩放：通过增加基因拷贝数或改变转录因子浓度来提升表达速率。
    • 垂直位移：通过引入非调节性输出源来提升基线表达水平。
    • 水平缩放：调节结合亲和力影响响应曲线的位置。
    • 曲线陡峭度：通过调节结合的合作性来影响响应曲线的陡峭程度。

  2. 实验结果：文献中报告了多种基于不同调节机制的响应曲线变化，展示了合成生物学在调节生物系统方面的广泛应用。

主要结论/意义/创新性 ​

本文总结了多种调节生物响应曲线的方法，为合成生物学的系统设计提供了重要的理论支持。调节生物系统的能力将推动复杂生物系统的构建，并为未来的生物工程应用奠定基础。文章强调了对调节机制的深入理解是实现合成生物学目标的关键。

研究局限性和未来方向 ​

研究的局限性在于文献综述并未涵盖所有可能的调节机制，且在不同生物系统中的适用性可能存在差异。未来的研究应聚焦于如何在实际应用中结合多种调节机制，以实现更复杂的生物系统设计。同时，研究者应关注生物系统的噪声效应及其对调节能力的影响，以提高系统的可靠性和一致性。

参考文献 ​

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  2. The second wave of synthetic biology: from modules to systems. - Priscilla E M Purnick;Ron Weiss - Nature reviews. Molecular cell biology (2009)
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  7. Transcriptional interference--a crash course. - Keith E Shearwin;Benjamin P Callen;J Barry Egan - Trends in genetics : TIG (2005)
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  9. TAL effectors: function, structure, engineering and applications. - Amanda Nga-Sze Mak;Philip Bradley;Adam J Bogdanove;Barry L Stoddard - Current opinion in structural biology (2013)
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引用本文的文献 ​

  1. Principles of genetic circuit design. - Jennifer A N Brophy;Christopher A Voigt - Nature methods (2014)
  2. Accurate, model-based tuning of synthetic gene expression using introns in S. cerevisiae. - Ido Yofe;Zohar Zafrir;Rachel Blau;Maya Schuldiner;Tamir Tuller;Ehud Shapiro;Tuval Ben-Yehezkel - PLoS genetics (2014)
  3. Improving fatty acids production by engineering dynamic pathway regulation and metabolic control. - Peng Xu;Lingyun Li;Fuming Zhang;Gregory Stephanopoulos;Mattheos Koffas - Proceedings of the National Academy of Sciences of the United States of America (2014)
  4. Design and characterization of a dual-mode promoter with activation and repression capability for tuning gene expression in yeast. - Mostafizur Mazumder;David R McMillen - Nucleic acids research (2014)
  5. Advances and computational tools towards predictable design in biological engineering. - Lorenzo Pasotti;Susanna Zucca - Computational and mathematical methods in medicine (2014)
  6. Impact of upstream and downstream constraints on a signaling module's ultrasensitivity. - Edgar Altszyler;Alejandra Ventura;Alejandro Colman-Lerner;Ariel Chernomoretz - Physical biology (2014)
  7. Synthetic biology outside the cell: linking computational tools to cell-free systems. - Daniel D Lewis;Fernando D Villarreal;Fan Wu;Cheemeng Tan - Frontiers in bioengineering and biotechnology (2014)
  8. Amplification of small molecule-inducible gene expression via tuning of intracellular receptor densities. - Baojun Wang;Mauricio Barahona;Martin Buck - Nucleic acids research (2015)
  9. Mechanistic links between cellular trade-offs, gene expression, and growth. - Andrea Y Weiße;Diego A Oyarzún;Vincent Danos;Peter S Swain - Proceedings of the National Academy of Sciences of the United States of America (2015)
  10. Modelling the effects of cell-to-cell variability on the output of interconnected gene networks in bacterial populations. - Nicolò Politi;Lorenzo Pasotti;Susanna Zucca;Paolo Magni - BMC systems biology (2015)

... (53 更多 篇文献)

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