Collaborative Research: Information Processing by Gene Regulatory Network Controlling Bacterial Sporulation

协作研究：控制细菌产孢子的基因调控网络的信息处理智力价值：有机体对各种环境提示做出反应而改变其表型的能力具有基本的生物学意义，但即使是研究最好的系统，其详细的机制也不完全清楚。土壤细菌枯草芽孢杆菌检测目前不明的饥饿线索，并通过其基因调控网络处理这些信息，导致孢子的形成。以这个简单的单细胞生物体为模型，这项研究的长期目标是发现基因调控网络信息处理的一般原理。具体地说，这个项目将揭示枯草杆菌如何在环境不确定的条件下处理信息，并在系统层面上做出适当的细胞命运决定。该方法的基石是体内和体外实验的结合，以及确定性(总体平均)和随机(单细胞)数学模型的结合。成功的关键是构建扰乱网络中各种过程的合成菌株，并比较它们对彼此和对野生型菌株的反应。实验结果将使用综合数学模型进行分析。这项研究的跨学科性质将揭示网络的信号响应特征和细胞命运决定如何受到其架构的影响。更广泛的影响：作为一个模式系统，枯草杆菌提供了显著的实验优势，包括强大的遗传工具、大量的突变菌株集合和完全测序的基因组。解开孢子形成网络的信息处理机制是在单细胞水平上理解细胞命运决定的分子基础的关键一步。因此，本项目中的创新方法可能适用于解决其他生物体中的类似问题，并可用于向不同水平和背景的学生教授系统级概念。特别是，合成菌株的集合可以用于本科实验室环境中的教育目的，因为它们的网络很容易受到不同诱导剂水平的干扰。因此，学生将了解网络体系结构和系统级别属性之间的关系。此外，数学模型可以作为系统生物学课程的基石。该项目还将为来自不同背景的参与学生提供丰富的跨学科培训机会，共同从事实验和/或数学建模工作。

Collaborative research: Information processing by gene regulatory network controlling bacterial sporulation Intellectual Merit: The ability of an organism to change its phenotype in response to various environmental cues is of fundamental biological importance, but the detailed mechanisms are not fully understood even for the best studied systems. The soil bacterium Bacillus subtilis detects currently unidentified starvation cues and processes this information via its gene regulatory networks, resulting in formation of a spore. Using this simple unicellular organism as a model, the long-term goal of this research is to discover general principles underlying the information processing by gene regulatory networks. Specifically, this project will uncover how B. subtilis processes information under conditions of environmental uncertainty and makes appropriate cell-fate decisions at the systems level. The cornerstone of the approach is a combination of in vivo and in vitro experiments as well as deterministic (population-average) and stochastic (single-cell) mathematical models. The key to success is the construction of synthetic strains which perturb various processes in the networks and the comparison of their responses to one another and to those in the wild-type strain. The experimental results will be analyzed using integrative mathematical models. The interdisciplinary nature of this research will uncover how signal-response characteristics and cell-fate decisions of the network are affected by its architecture. Broader Impacts: As a model system, B. subtilis offers significant experimental advantages including powerful genetic tools, large collections of mutant strains, and a fully sequenced genome. Unraveling the mechanisms of information processing by the sporulation network is a key step towards understanding the molecular basis of cell-fate decision at the unicellular level. Thus, the innovative approaches in this project may be applicable for addressing similar problems in other organisms and can be used for teaching system-level concepts to students of various levels and backgrounds. In particular, the resulting collection of synthetic strains can be used for educational purposes in the undergraduate laboratory setting because their networks are easy to perturb by varying the inducer levels. As a result, students will gain an understanding of the relationship between network architecture and system level properties. In addition, mathematical models can be used as a cornerstone for systems biology curriculum. The project will also provide abundant interdisciplinary training opportunities for the participating students from various backgrounds working together on experimental and/or mathematical modeling.