CAREER: Engineering Biological Robustness through Synthetic Control

1350498文泰锡 天然调控网络具有复杂的特征，以确保强大的细胞功能。 然而，健壮性是有代价的：它需要细胞资源，给细胞带来代谢负担。该项目的总体目标是通过自下而上构建遗传电路来理解生物鲁棒性的原则。 这项工作将通过提供设计原则和工程策略来造福社会，以确保生物系统在很长一段时间内按照设计的方式运行。此外，虽然PI的重点是将设计原则应用于生化生产平台，但通过用有毒化学降解途径和病原体杀灭机制取代致动器模块，可以将相同的方法应用于其他问题，例如环境和健康问题。 该项目的总体目标是通过自下而上构建遗传电路来理解生物鲁棒性的原则。这个项目的智力价值有三个方面。首先，它将能够对单个基因施加的负担进行定量评估，为合成生物学中的部分选择提供指导。其次，它将有助于解决代谢负担和进化的问题，通过使用遗传电路。最后，通过自下而上构建功能，将测试关于高度互连的自然监管网络的动态和演变的假设。 研究方法将涉及（i）识别和表征的感觉和基因调控元件，（ii）负反馈回路和冗余电路的建设，以及（iii）这些合成电路在微生物细胞工厂的化学和药物生产的实施。

1350498Moon, Tae Seok Natural regulatory networks have complex features to ensure robust cellular functions. However, robustness comes with a price: it requires cellular resources, imposing a metabolic burden on cells. The overarching goal of this project is to understand the principles of biological robustness by building genetic circuits from the bottom-up. The work will benefit society by providing design principles and engineering strategies to ensure that biological systems behave as designed over a long time scale. In addition, while the PI's focus is to apply design principles to biochemical production platforms, the same approach can be applied to other problems, such as environmental and health issues, by replacing the actuator modules with toxic chemical degrading pathways and pathogen killing mechanisms. The overarching goal of this project is to understand the principles of biological robustness by building genetic circuits from the bottom-up. The intellectual merits of this project are threefold. First, it will enable the quantitative assessment of the burden imposed by individual genes, providing guidelines for part selection in synthetic biology. Second, it will help address the issues of metabolic burden and evolution by using genetic circuits. Last, by building functions from the bottom-up, hypotheses regarding the dynamics and evolution of highly interconnected natural regulatory networks will be tested. The research approach will involve (i) the identification and characterization of sensory and gene regulatory elements, (ii) the building of negative feedback loops and redundant circuits, and (iii) the implementation of these synthetic circuits in microbial cell factories for chemical and drug production.