细菌趋化信号网络多路输出的协调

Life science studies are getting more quantitative and systematic; this makes it more wide-spread and important to apply ideas and techniques from Physics to Life science studies. A central question in Life science is to understand how molecular-level stimuli in the environment are converted to cellular behavioral responses. This conversion is usually accomplished by various kinds of biological networks, such as neuronal, signal transduction, and gene regulation networks. Among biological networks, there are often examples of individual network controlling multiple stochastic outputs. This raises the ubiquitous question of how a biological network coordinates its outputs to respond to a single input. The bacterial chemotaxis signaling network, because of its clear and prototypical architecture, has been a good model system for us to gain insights to this question. The bacterial flagellar motor is the output of the chemotaxis network. The chemotaxis network controls the rotational direction of multiple flagellar motors on a bacterium, so that the bacterium can perform biased 3D random walk following a run-and-tumble pattern, to swim towards environments it deems beneficial. In this project, we will systematically study how the chemotaxis network coordinates multiple flagellar motors, and understand the behavioral significance of motor coordination. Studies of how bacterial chemotaxis network coordinates its multiple outputs will promotes the understanding of other biological networks, and help to look for general principles of how a network coordinates its multiple outputs.

当前生命科学的研究越趋定量化和系统化，这使得物理的思想和手段在其中的应用日趋广泛和重要。生命科学的核心问题之一是理解外界环境中分子水平的刺激如何被细胞感知并转换成细胞水平的行为响应。这通常由各种生物网络完成，比如神经、信号传导、及基因调控网络。在这些网络中，经常有单个网络控制多个随机运行的输出端的例子。因此，生物网络如何协调控制多路输出端是一个普遍存在的问题。细菌趋化网络由于其架构的清晰性和典型性，为研究这个问题提供了一个极好的模型网络。鞭毛马达是细菌趋化网络的输出端。这个信号网络控制细菌上多个鞭毛马达的转动方向，从而使细菌交替"直线运动-原地翻转"，进行有偏向性地随机游动，以趋向对细菌有利的环境。本项目将系统研究趋化信号网络如何协调多个马达的运行，并理解这种马达协调在细菌行为上的意义。对细菌趋化网络多路输出端协调机制的研究将有助于理解其它生物网络，并有助于寻找网络输出协调的普适规律。

生物信号网络如何协调控制其多路输出端是一个普遍存在的问题。细菌趋化网络是研究此问题的一个典型网络。鞭毛马达是其输出端。趋化信号网络控制细菌上多个鞭毛马达的转动方向，以趋向对细菌有利的环境。我们在项目执行过程中，取得了以下主要成果：1）结合纳米金球标记马达及激光暗场技术，发展了对马达转向改变动力学准确观测的实验手段。2）系统研究了协调控制多个马达的机制之一：趋化信号网络的噪声，准确测量了噪声幅度，并发现此噪声能提高趋化灵敏度。3）系统探索了趋化信号网络多路输出端协调机制，分析了两个机制（网络噪声及成束鞭毛力学耦合）的分别贡献，并探索了输出端协调在细菌趋化行为上的意义。4）发现了鞭毛马达别构调控的非平衡机制。5）对鞭毛马达力矩产生动力学进行了准确测量。6）发现细菌能适应其生长条件而调节其趋化行为。在本项目执行期间，共发表通讯作者SCI论文5篇，包括Nature Physics 1篇，PNAS 2篇，Biophysical Journal 1篇，Phys. Rev. E 1篇。其它一些重要结果也已投稿。