Enhancing Robustness of Gene Regulatory Networks

增强基因调控网络的稳健性

• 批准号: 1515280
• 负责人: Kyung Kim
• 金额: $ 50万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1515280&HistoricalAwards=false
• 关键词: Enhancing; Robustness; Gene; Regulatory; Networks

Robustness in synthetic genetic circuits is a central issue for the reliable operation of engineered genetic devices. This project is anticipated to uncover principles of genetic circuit design that can lead to the robust performance of such engineered devices. The research will also advance our understanding of the functional life span of synthetically engineered organisms in different environments, and aid in devising active mechanisms to enhance or attenuate robustness. The wider implication of this this research is that it can help to provide a "safety net" that limits the survivability of engineered organisms that escape or are released into the environment. The project provides training opportunities through the development of laboratory courses that integrate bio-engineering principles with concepts of robustness and bio-safety.This project will develop design principles for enhancing the functional robustness of engineered cells using genetic homology and gene network topology. When introduced into host organisms, genetically engineered devices or synthetic genetic networks will be subjected to continuous perturbations due to changes in cellular processes and environmental factors, and the synthetic genetic components themselves operate stochastically due to the random nature of the underlying biochemical processes. Engineering robust genetic circuits under mutation pressures (whereby mutated strains quickly outgrow the original engineered strain) is one of the key challenges for synthetic biology. This project will take a step toward designing robust synthetic circuits by applying integrated mathematical, computational, and experimental approaches, where the goal is to model such fitness changes to enable the design of controlled functional robustness. The fitness landscape design concept will be tested in synthetic circuits implemented in E. coli. This study will help the analysis and prediction of the degree of robustness of synthetic genetic circuits, and help to identify and correct mutation-prone genetic components and network structures.

合成遗传回路的鲁棒性是工程遗传设备可靠运行的核心问题。预计该项目将揭示遗传回路设计的原则，这些原则可能会导致此类工程设备的出色性能。这项研究还将提高我们对不同环境中合成生物的功能寿命的理解，并有助于制定主动机制以增强或减弱鲁棒性。这项研究的更广泛含义是，它可以帮助提供一个“安全网”，以限制逃脱或释放到环境中的工程生物的生存能力。该项目通过开发实验室课程提供培训机会，这些课程将生物工程原理与稳健性和生物安全的概念相结合。该项目将开发设计原理，以使用遗传同源性和基因网络拓扑来增强工程细胞的功能鲁棒性。 当引入宿主生物时，由于细胞过程和环境因素的变化，基因工程的设备或合成遗传网络将受到连续扰动，并且由于基本生物化学过程的随机性质，合成遗传成分本身会在平稳上进行。突变压力下的工程强大的遗传回路（从而突变菌株很快超过了原始工程菌株）是合成生物学的关键挑战之一。该项目将通过应用集成的数学，计算和实验方法来迈向设计鲁棒合成电路的一步，在这种方法中，目标是建模这种适应性的变化以实现受控功能稳健性的设计。健身景观设计概念将在大肠杆菌中实施的合成电路中进行测试。这项研究将有助于分析和预测合成遗传回路的鲁棒性程度，并有助于识别和纠正容易突变的遗传成分和网络结构。