生物调控系统中的能量消耗及超越

Regulation means breaking of detailed balance, so biological regulatory systems existing extensively in the natural word definitely consume energy. However, some fundamentally important issues such as how energy consumption in these systems are characterized and how the relationship between biological regulation function and energy consumption is described remain to be fully unsolved. Owing to complexity of biomolecular systems (e.g., they would involve difference in time and space scales, inherent stochasticity, diversity of topological structure, etc), this will aggravate difficulty of related studied. Aiming the limitation of existing theories and methods, this project tries to establish a binomial moment method used for dealing with the reaction- diffusion master equation, and uses it to investigate energy consumption in biological regulatory systems. The investigation is done along two lines: The one is to study the relationship between information transmission and energy consumption in gene regulatory systems, and at this study stage, influences of stochastic fluctuations in extracellular signals, feedback regulation, and interaction between transcription factors will be simultaneously considered; The other is to study the relationship between biological function and energy consumption in bistable or oscillatory systems, and at this study stage, influence of the change in network topology will be considered. Through these studies, we try to reveal universal laws for energy consumption in biological regulatory systems, which would lay a solid theoretical foundation for better understanding intracellular processes. Related studies have potential applications in fields such as biopharmaceutical and gene therapy.

调控意味着细致平衡的打破，因此自然界中普遍存在的生物调控系统必然消耗能量。然而，如何特征化这种系统中的能量消耗以及如何刻画出生物调控功能与能量消耗之间的关系等基本重要问题并未完全解决。由于生物分子系统的复杂性（如涉及时空尺度的差异性、固有的随机性、网络拓扑的多样性等），这将加重相关研究的难度。本项目将针对现有理论和方法的局限，研究建立处理反应扩散主方程的空间二项矩方法，并应用它来研究生物调控系统中的能量消耗等问题。研究分两条线路进行：一是研究基因调控系统中信息传递与能量消耗之间的关系，研究时将考虑细胞外部信号的波动、反馈调控、以及转录因子作用的影响等；二是研究双稳或振荡生物系统中生物功能与能量消耗之间的关系，研究时将考虑网络拓扑的影响。通过这些研究，试图揭示出生物调控系统中能量消耗的一般规律，为进一步理解细胞内部过程打下坚实的理论基础。相关研究在生物制药、基因理疗等方面具有潜在的应用背景。

本项目主要研究生物调控系统中的能量消耗，应用提出的理论和方法探讨调控机制、信息传输、生物学功能与能量消耗的关系。首先，研究了转录水平上基因调控模型，探讨了不同调控机制下的基因表达动力和能量消耗，发现转录因子的调控作用和分子记忆重要地影响着基因表达能量消耗。其次，提出了一种求解动态反应速率的生化反应系统的动态概率分布的方法，并用来研究了两个典型信号模块中的解析动态分布，在此基础上进一步探讨了典型信号模块中的能量消耗。第三，研究了连续和爆发系统中信息传输和噪声的关联, 发现两种信号机制中的输出噪声和信息传输成反比。最后，基于概率主方程和微观马氏链方法，探讨了两个传染病模型，提出了相应的动态随机控制策略。通过本项目的研究，希望能够为进一步理解细胞内部过程和生物学功能提供理论基础。项目申请者公开发表或接受发表相关学术论文6篇，还有1篇已投稿。较好地完成计划任务书中的预期成果指标。