Stability and Robustness of Genetic Toggle Switches

遗传拨动开关的稳定性和鲁棒性

基本信息

  • 批准号:
    0417721
  • 负责人:
  • 金额:
    $ 43.83万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-07-01 至 2007-06-30
  • 项目状态:
    已结题

项目摘要

Because the number of genes an organism possesses is limited and the number of functions each gene can perform is also limited, coordinated activities of a group of genes are necessary for a cell to execute many complex tasks. However, very little is known about the organization and evolution of such gene networks. In this research, a combined in vivo/in vitro evolution approach will be used to "breed" genetic circuits of various properties. The focus will be on the simplest, and the best-characterized class of genetic circuits, the two-gene "toggle switch". Molecular and evolution experiments will be performed to investigate a number of issues concerning the function and evolution of this system. Specifically, the proposed evolutionary method will be used to generate switches with varying degrees of stability with respect to spontaneous switching by cellular noise. The evolved regulatory sequences will be analyzed to identify features that correlate with different degrees of circuit stability. The robustness of these switches to mutation will also be characterized, and possible relationship between the system's stability to noise and its robustness to mutation will be investigated. Finally, the dynamics of the switch evolution will be probed by sequencing the evolved regions at various intermediate stages of the evolution process. Broader impacts of this research include the training of a new generation of students at the interface and the forefront of biophysics, molecular biology, and evolution, and the development of experimental protocols to evolve designer genetic circuits for a variety of bioengineering and biomedical applications.
由于生物体拥有的基因数量有限,每个基因可以执行的功能数量也有限,因此一组基因的协调活动对于细胞执行许多复杂的任务是必要的。然而,人们对这种基因网络的组织和进化知之甚少。在这项研究中,结合体内/体外进化的方法将被用来“繁殖”各种属性的遗传电路。重点将放在最简单的,最好的遗传电路,两个基因的“拨动开关”。将进行分子和进化实验,以研究有关该系统的功能和进化的一些问题。具体而言,所提出的进化方法将被用来产生不同程度的稳定性相对于自发切换蜂窝噪声开关。进化的调控序列将进行分析,以确定与不同程度的电路稳定性相关的功能。这些开关突变的鲁棒性也将被表征,并将研究系统对噪声的稳定性与其对突变的鲁棒性之间的可能关系。最后,将通过对进化过程各个中间阶段的进化区域进行测序来探索开关进化的动态。这项研究的更广泛的影响包括在生物物理学,分子生物学和进化的界面和前沿的新一代学生的培训,以及实验协议的发展,以发展设计师的遗传电路的各种生物工程和生物医学应用。

项目成果

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Terence Hwa其他文献

The Growth of Bacterial Colonies
  • DOI:
    10.1016/j.bpj.2011.11.831
  • 发表时间:
    2012-01-31
  • 期刊:
  • 影响因子:
  • 作者:
    Mya Warren;Terence Hwa
  • 通讯作者:
    Terence Hwa
Anomalous fluctuations of directed polymers in random media.
随机介质中定向聚合物的异常波动。
Topological order in the vortex-glass phase of high-temperature superconductors
高温超导体涡旋玻璃相的拓扑顺序
  • DOI:
    10.1103/physrevb.55.626
  • 发表时间:
    1995
  • 期刊:
  • 影响因子:
    0
  • 作者:
    J. Kierfeld;J. Kierfeld;T. Nattermann;Terence Hwa
  • 通讯作者:
    Terence Hwa
Crumpled and collapsed conformation in graphite oxide membranes
氧化石墨膜中的褶皱和坍塌构象
  • DOI:
    10.1038/355426a0
  • 发表时间:
    1992-01-30
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Xin Wen;Carl W. Garland;Terence Hwa;Mehran Kardar;Etsuo Kokufuta;Yong Li;Michal Orkisz;Toyoichi Tanaka
  • 通讯作者:
    Toyoichi Tanaka
Marine bacteria emAlteromonas/em spp. require UDP-glucose-4-epimerase for aggregation and production of sticky exopolymer
海洋细菌 Alteromonas spp. 需要 UDP-葡萄糖-4-表异构酶来进行聚集和产生粘性胞外聚合物。
  • DOI:
    10.1128/mbio.00038-24
  • 发表时间:
    2024-07-26
  • 期刊:
  • 影响因子:
    4.700
  • 作者:
    Jacob M. Robertson;Erin A. Garza;Astrid K. M. Stubbusch;Christopher L. Dupont;Terence Hwa;Noelle A. Held
  • 通讯作者:
    Noelle A. Held

Terence Hwa的其他文献

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{{ truncateString('Terence Hwa', 18)}}的其他基金

Elucidating the origin and consequences of dimensional reduction in bacterial growth control
阐明细菌生长控制中降维的起源和后果
  • 批准号:
    1818384
  • 财政年份:
    2018
  • 资助金额:
    $ 43.83万
  • 项目类别:
    Continuing Grant
Experimental and Theoretical Characterization of Metabolic Coordination
代谢协调的实验和理论表征
  • 批准号:
    1058793
  • 财政年份:
    2011
  • 资助金额:
    $ 43.83万
  • 项目类别:
    Continuing Grant
Quantitative Studies of Nitrogen Assimilation & Its Control in Enteric Bacteria: From Molecules to Physiology
氮同化的定量研究
  • 批准号:
    0746581
  • 财政年份:
    2008
  • 资助金额:
    $ 43.83万
  • 项目类别:
    Continuing Grant
Statistical Mechanics of Gene Regulation
基因调控的统计机制
  • 批准号:
    0211308
  • 财政年份:
    2002
  • 资助金额:
    $ 43.83万
  • 项目类别:
    Continuing Grant
Statistical Mechanics of Sequence Matching
序列匹配的统计机制
  • 批准号:
    9971456
  • 财政年份:
    1999
  • 资助金额:
    $ 43.83万
  • 项目类别:
    Continuing Grant

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跨多个环境的科学发现:遗传关联研究的复制性、稳健性和公平性
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  • 批准号:
    10831121
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  • 批准号:
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Genetic analysis of the Dutch Hunger Winter Families Study to Boost Rigor and Robustness for Testing In-Utero Famine Effects on Aging-Related Health Conditions and Biological Aging
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Genetic analysis of the Dutch Hunger Winter Families Study to Boost Rigor and Robustness for Testing In-Utero Famine Effects on Aging-Related Health Conditions and Biological Aging
荷兰饥饿冬季家庭研究的遗传分析,以提高测试宫内饥荒对衰老相关健康状况和生物衰老影响的严谨性和稳健性
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