Institute for Medical Engineering and Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email:
Harvard-MIT Program in Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.
Annu Rev Biophys. 2018 May 20;47:399-423. doi: 10.1146/annurev-biophys-070816-033903. Epub 2018 Mar 16.
Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.
工程合成基因调控回路是通过设计、构建和测试的迭代循环进行的。初始电路设计必须依赖于通过简化研究领域（生物化学、分子和系统生物学）建立的、通常不完整的调控模型。由于不可避免地会遇到设计和实验观察到的电路行为之间的差异，并且需要对其进行调查和解决，因此工程循环的每一次迭代都可以迫使重新综合理解自然网络功能。在这里，我们概述了使用基因电路工程的研究来推动生物学发现。合成基因电路工程研究不仅使我们对细胞调控有了更深入的了解，而且为生物学家提供了一种工具包，可以直接针对自然系统进行精确的网络结构操作。正如我们所讨论的，使用电路工程对细胞调控进行预测性地重新组织、重新布线和重构，是测试和理解细胞表型如何从系统级网络功能中出现的最终手段。
