《生命科学》 2021, 33(12): 1445-1451

人工基因回路设计原理的进展与挑战

项延会 , 李婷婷 , 娄春波^*

中国科学院深圳先进技术研究院，合成生物学研究所，细胞与基因线路研究中心，深圳 518055

摘　要：

人工基因回路是在生命体中设计的“细胞信息处理器”，可以按照理论预测功能完成对生命体内外环境信号的动态感应与信息整合，并控制细胞个体与细胞群体的代谢、稳态和发育分化行为。由于生命体是微体积、高噪声、非线性的动态复杂系统，而且面临生态竞争和进化变异等生物特有因素，因此基因线路设计的对象是可进化的复杂反馈系统，需要利用定性或定量的系统理论模型进行某种程度的预测，并在理论预测的指导下，利用各种模块化和正交化的优质调控元件构建完成。在过去二十年，基因回路设计的基础原理取得了巨大的成功，阐明了模块化、绝缘化、正交化和鲁棒性设计等基本设计规律，成功地构建了一大批基因回路。随着超大规模基因回路( 包含10 个以上调控基因) 和非简单模式生物基因回路的出现，基因线路的模块化和正交化等设计理论遇到了严重的挑战。该文将主要综述基因回路设计理论的进展，并着重阐述基因回路设计的已有基础与未来挑战。

通讯作者：娄春波 , Email:cb.lou@siat.ac.cn

Progresses and challenges for the fundamental design principles of genetic circuits

XIANG Yan-Hui , LI Ting-Ting , LOU Chun-Bo^*

Center for Cell and Gene Circuit Design, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China

Abstract:

Genetic circuits are the information processor in a living cell or whole life, which could implement sophisticated regulatory or signaling function based on the theoretical design. The circuits sense the external and internal environmental signals, integrate and compute the information, control the metabolism, homeostasis and development in the single cell and multiple cell levels. The living cell is a tiny volume, high noise and nonlinear dynamical complex system, and also encountering the ecological competition and evolutionary mutations. We thus need to develop nonlinear dynamical models to qualitatively and quantitatively predict their functions, and then utilize the high-quality modular and orthogonal parts to assemble as the functional circuits. In the past two decades, the fundamental design principles have made substantial progresses, raised several guided-rules, such as modularity, orthogonality, insulation and robustness design, and so on. However, these developed fundamental rules hardly meet the need of the design of super-large genetic circuits and the simple circuits in complex host contexts. We review the recent progresses of the design principles of genetic circuits, and especially address the future challenges todesign super-large genetic circuits and the circuits in complex host and environmental contexts.

Communication Author：LOU Chun-Bo , Email:cb.lou@siat.ac.cn