C-Signal-Dependent Gene Expression in Myxococcus Xanthus

在自然界中，细菌通常以称为生物膜的社区成员的形式存在。生物膜的发展涉及细胞相互发送信号并改变其基因表达作为回应。了解细菌在生物膜形成过程中如何调节基因以响应细胞间的相互作用是一个具有重大实际意义的基本挑战。粘球菌xanthus提供了一个非常有吸引力的实验系统，以解决这一挑战。当饥饿时，细胞移动到聚集中心并构建新生的子实体。在子实体内，杆状细胞分化成球形休眠孢子。细胞之间的信号传导对于这个发育过程至关重要。C-信号转导在M. xanthus的发展正在为细菌细胞如何相互作用和调节基因建立一个新的范例。C信号涉及CsgA，一种在发育细胞中水平升高的蛋白质。CsgA与细胞表面结合并介导细胞之间的短程信号传导。C-信号传导在受体细胞中诱导几种反应。它调节细胞运动、基因表达和孢子形成。对CsA信号的不同响应需要不同水平的CsA。CsgA水平的上升和细胞进入聚集体时细胞之间接触的增加可能确保导致孢子形成的基因表达所需的高水平C-信号传导仅发生在子实体内。该项目的长期目标是了解响应C信号的差异基因表达如何调节子实体发育。过去的支持导致发现C-信号依赖基因是在转录因子的组合控制下。一个反复出现的主题是MrpC和FruA的参与，但一些基因需要额外的转录因子。该项目的目的是：1）确定MrpC和FruA在特定启动子上的作用，2）在全基因组范围内鉴定MrpC和FruA的直接靶点，3）发现C信号依赖基因的其他转录因子。预计该项目的结果将为细菌如何调节基因和控制细胞行为以响应具有实际重要性的生物膜中的信号提供范例，从而促进发现操纵生物膜生长的方法。此外，该项目将通过本科生、研究生和博士后的教学和培训，为科学人力资源的开发做出贡献。

In nature, bacteria often exist as members of communities called biofilms. The development of biofilms involves cells sending signals to each other and changing their gene expression in response. Understanding how bacteria regulate genes in response to cell-cell interactions during biofilm development is a fundamental challenge of great practical significance. Myxococcus xanthus provides a very attractive experimental system to address this challenge. When starved, cells move to aggregation centers and construct a nascent fruiting body. Within the fruiting body, rod-shaped cells differentiate into spherical, dormant spores. Signaling between cells is essential for this developmental process. Studies of C-signaling during M. xanthus development are establishing a new paradigm for how bacterial cells interact and regulate genes. C-signaling involves CsgA, a protein whose level rises in developing cells. CsgA becomes associated with the cell surface and mediates short-range signaling between cells. C-signaling induces several responses in recipient cells. It regulates cell movements, gene expression, and sporulation. The different responses to Csignaling require different levels of CsgA. The rising level of CsgA and the increased contacts between cells as they enter aggregates may ensure that the high level of C-signaling required for gene expression leading to sporulation only occurs within the fruiting body. The long-term goal of this project is to understand how differential gene expression in response to C-signaling regulates fruiting body development. Past support led to the discovery that C-signal-dependent genes are under combinatorial control of transcription factors. A recurring theme is the involvement of MrpC and FruA, but some genes require additional transcription factors. The aims of the project are 1) to determine the roles of MrpC and FruA at particular promoters, 2) to identify the direct targets of MrpC and FruA genome-wide, and 3) to discover additional transcription factors of C-signal-dependent genes. It is anticipated that the results of the project will provide paradigms for how bacteria might regulate genes and control cell behavior in response to signals in biofilms of practical importance, facilitating discovery of ways to manipulate biofilm growth. Also, the project will contribute to the development of human resources in science through the teaching and training of undergraduates, graduate, and postdoctoral students.