基于动力学分析的合成生物学研究

王瑞琦; 陈洛南

doi:10.12211/2096-8280.2023-001

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基于动力学分析的合成生物学研究

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- 基于动力学分析的合成生物学研究
- Synthetic biology based on dynamical analysis
- 合成生物学 2024年5卷第1期页码：77-87
- 作者机构：
  
  1.上海大学数学系，上海 200444
  2.中国科学院分子细胞科学卓越创新中心，上海生物化学与细胞生物学研究所系统生物学重点实验室，上海 200031
  3.浙江省系统健康科学重点实验室，中国科学院中国科学院大学杭州高等研究院，浙江杭州 310024
- 作者简介：
  
  [ "王瑞琦（1974—），男，研究员，博士生导师。研究方向为计算生物学与非线性动力学中稳定性、摄动、与分支理论等。 E-mail：rqwang@shu.edu.cn" ]
  [ "陈洛南（1962—），男，研究员，博士生导师。研究方向为网络生物学、计算生物学、机器学习与人工智能等。 E-mail：lnchen@sibcb.ac.cn" ]
- 基金信息：
  
  国家自然科学基金(12371497;12131020;31930022;12026608);国家重点研发计划(2017YFA0505500);中国科学院战略优先研究计划(XDB38040400);华大基因深圳开放项目(BGIRSZ20210010)
- DOI：10.12211/2096-8280.2023-001
  中图分类号： Q816
- 收稿：2022-12-31，
  
  修回：2023-07-04，
  
  纸质出版：2024-02-29
- 稿件说明：
移动端阅览
王瑞琦，陈洛南. 基于动力学分析的合成生物学研究［J］. 合成生物学， 2024， 5（1）： 77-87

WANG Ruiqi， CHEN Luonan. Synthetic biology based on dynamical analysis［J］. Synthetic Biology Journal， 2024， 5（1）： 77-87
王瑞琦，陈洛南. 基于动力学分析的合成生物学研究［J］. 合成生物学， 2024， 5（1）： 77-87 DOI： 10.12211/2096-8280.2023-001.

WANG Ruiqi， CHEN Luonan. Synthetic biology based on dynamical analysis［J］. Synthetic Biology Journal， 2024， 5（1）： 77-87 DOI： 10.12211/2096-8280.2023-001.

摘要

随着生物技术与其他各学科如计算科学的发展，合成生物学在功能设计与实验实施方面都取得了长足的进展。合成生物学近年来在计算生物学与人工智能等交叉学科领域引起广泛兴趣。从数学科学的角度，设计各种具有特定功能的合成生物元件的理论不断涌现，如基因开关、基因振子、生物逻辑门等。从生物技术角度，基因工程、蛋白（酶）的化学修饰自组装等生物合成及功能化策略也取得了巨大进步。这些相关方面的长足发展，也大大促进了合成生物学的发展。本文重点从生物分子网络动力学的角度，深入阐述各种具有特定功能的合成生物网络背后的理论基础与分析方法，其中包括生物功能器件如开关与振子，以及数学与网络理论相关的因素，包括正负反馈回路与动力学的相关性、非线性因素与时间延迟产生的原因、稳定性与分支相关理论、周期振子的鲁棒性、周期可调性等动力学相关的理论基础与分析方法，为进一步设计更为复杂或者更易实验合成的生物器件提供可以借鉴的理论分析方法。

Abstract

With the developments of biotechnology and other disciplines such as computational science

synthetic biology has made great progresses in theoretical analysis

functional design

and experimental implementation

which is attracted extensively in the interdisciplinary fields such as computational biology and artificial intelligence. From the perspective of mathematical science

theories of designing various synthetic biological elements with specific functions have been emerging

such as gene switches

gene oscillators

and biological logic gates. From the perspective of technological innovation

great progresses have been made in biosynthesis and functionalization strategies such as genetic engineering and chemical modifications on proteins (enzymes) for self-assembly. The rapid developments of these related aspects have also greatly promoted the development of synthetic biology. This review specifically focuses on theoretical basis and analysis methods behind various synthetic biological networks with specific functions from the perspective of biomolecular network dynamics

including functional biological devices such as switches and oscillators

as well as factors related to mathematics and network theory

including correlations between positive and negative feedback loops and nonlinear dynamics

nonlinear factors and the causes of time delays

stability and bifurcation-related theories

and theoretical basis and analysis methods related to dynamics

such as the robustness and period tunability of periodic oscillators are also addressed

which provides theoretical analysis methods that can be used as reference for further design of more complex or easily synthesized biological devices. Therefore

synthetic biology based on dynamics can start with mathematical modeling and dynamical system theory to construct synthetic gene regulatory networks with specific functions. By applying gene editing technology and adopting reasonable assembly strategies for experimental manipulations

we can verify the theoretical designs. By analyzing gene expression profiles

the feasibility and performance of the theoretical design can be explored. Further analysis of the topology and function of synthetic gene regulatory networks

as well as relationship between dynamics and parameters can help us better understand adjustable design strategies and key factors for redesign.

关键词

Keywords

references

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