Systems Analysis of the Sporulation Initiation Network in the Bacterium Bacillus subtilis

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。智力优势：大多数生物过程，如分化、生长、发育和转化，都受到细胞信号系统的严格控制。然而，细胞如何决定何时何地执行这些过程的详细机制仍然是现代生物学的一大谜团。在简单的单细胞生物体中发现信号转导的一般原理是理解遗传和生物化学网络复杂性的重要一步。因此，细菌的感觉行为是探索细胞信号传导、分化和发育的分子基础的有力模型。土壤细菌枯草芽孢杆菌中的孢子形成是研究得最好的模型系统之一，但细胞命运决定的机制仍远未被理解。该项目的长期目标是揭示细菌细胞如何在孢子形成过程中处理信号以做出细胞决定。作为实现这一目标的一步，该项目的目的是阐明系统特性的磷酸化孢子形成启动网络与湿实验室实验，计算数据分析和数学建模的协同组合。该项目还解决了关于种群异质性，噪声，综合系统行为和对环境刺激的决策之间关系的基本生物学问题。更广泛的影响：预计项目结果将揭示新的机制，通过这些机制，环境线索被测量并转化为基因表达和随后分化的动态变化。所揭示的机制可普遍适用于许多生物体中复杂发育过程的研究。本研究中的模式生物与引起食品腐败的微生物密切相关。孢子的异质性敏感性和抗性是食品保藏的一个众所周知的障碍，可能最终与孢子形成程序执行中的可变性有关。 对本科生和研究生的培训是该项目的一个组成部分，项目负责人致力于与受训人员密切合作。PI将继续努力通过现有的机构计划从代表性不足的少数群体中招募学生进入他们的实验室。该项目将为参与其实验和/或数学建模方面的学生提供丰富的机会，协同工作，从而培养能够有效弥合生物科学和定量学科之间差距的科学家。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Intellectual Merit: The majority of biological processes such as differentiation, growth, development and transformation are under tight control of cellular signaling systems. However, detailed mechanisms of how cells decide when and where to execute these processes remains one of the great mysteries of modern biology. Discovery of general principles underlying signal transduction in a simple unicellular organism is an essential step towards understanding the complexity of genetic and biochemical networks. Sensory behaviors of bacteria therefore serve as powerful models for exploring the molecular basis of cell signaling, differentiation and development. Sporulation in the soil bacterium Bacillus subtilis is one of the best studied model systems but the mechanisms of cell-fate decisions are still far from understood. The long-term goal of this project is to reveal how bacterial cells process signals to make cell decisions during sporulation. As a step toward that goal, this project aims to elucidate systemic properties of the phosphorelay sporulation initiating network with a synergistic combination of wet-lab experimentation, computational data analysis and mathematical modeling. The project also addresses fundamental biological questions on the relationship between population heterogeneity, noise, integrated system behavior, and decision making in response to environmental stimuli. Broader Impacts: Project results are expected to unravel novel mechanisms by which environmental cues are measured and converted into dynamic changes in gene expression and subsequent differentiation. The uncovered mechanisms can be generally applicable to studies of complex developmental processes in a number of organisms. The model organism in this study is closely related to those causing food spoilage. Heterogeneity in sensitivity and resistance of spores, a well known obstacle of food preservation, may be ultimately related to variability in the execution of the sporulation program. The training of undergraduate and graduate students is an integral part of this project and the PIs are committed to working closely with trainees. The PIs will continue their efforts to recruit students from underrepresented minority groups into their labs through existing institutional programs. The project will provide abundant opportunities for the students involved in its experimental and/or mathematical modeling aspects to work together synergistically and therefore train scientists capable of effectively bridging the gaps between the biological sciences and quantitative disciplines.