C-Signal-Dependent Gene Expression in Myxococcus Xanthus

在自然界中，细菌通常作为生物膜群落的成员存在。生物膜的形成涉及细胞相互发送信号并改变其基因表达作为回应。了解细菌在生物膜发育过程中如何调控基因以响应细胞间相互作用是一项具有重要现实意义的基础性挑战。黄粘球菌提供了一个非常有吸引力的实验系统来解决这一挑战。当饥饿时，细胞移动到聚集中心，形成新生的子实体。在子实体内，杆状细胞分化成球形的休眠孢子。细胞间的信号传递对这一发育过程至关重要。c -信号的研究为细菌细胞如何相互作用和调控基因建立了一个新的范式。c信号传导涉及CsgA，一种在发育细胞中水平上升的蛋白质。CsgA与细胞表面相关，并介导细胞间的短距离信号传导。c信号在受体细胞中诱导多种反应。它调节细胞运动、基因表达和产孢。对c信号的不同反应需要不同水平的CsgA。CsgA水平的上升和细胞进入聚集体时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信号只发生在子实体内。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的发育。过去的支持导致发现c信号依赖基因受转录因子的组合控制。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在特定启动子中的作用，2)确定MrpC和FruA全基因组的直接靶点，以及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生物膜中具有实际意义的信号提供范例，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，促进科学人力资源的发展。

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.