Molecular Mechanisms of Non-coding Bacterial Small RNAs in a Model Quorum Sensing System

智力优势：本研究的总体目标是了解非编码小rna （sRNAs）在控制细菌细胞过程中的作用，包括在环境中的生存。霍乱弧菌利用细胞间通讯或群体感应（QS）来同步调节四种Qrr rna（群体调节rna）的表达，以响应细菌群体的密度。最近的研究表明，与其他细菌sRNAs一样，Qrr sRNAs可以调控多个靶基因。虽然霍乱弧菌是一种短暂的人类病原体，但它是水生河口和海洋生态系统的常见居民。本研究项目旨在利用对霍乱弧菌模型QS系统的理解，发现Qrr sRNAs在不同环境下影响微生物行为的作用。具体而言，该项目将解决以下目标。目的1：鉴定受群体感应调节的sRNAs控制的基因。目的2：利用遗传、生化和计算方法定义sRNA调控的分子机制。目的3：评估不同地点分离的霍乱弧菌菌株QS回路和功能的保守性。由于sRNAs在生命的所有领域都参与了重要的生物学功能，因此确定这些sRNAs的作用机制将对理解所有细胞系统的调控回路具有根本性的意义。此外，细菌细胞-细胞通信系统广泛存在于环境、商业和临床意义重大的微生物中。了解这些信号通路如何发挥作用，以及它们如何控制环境中的细菌生存，最终可以制定策略，以减少世界范围内的环境、人类、动物和植物健康问题。更广泛的影响：申请人从事教学和服务活动，旨在传播现代科学发现，促进学术界成员和更广泛的社会之间的互动。对学生的培训包括教授一门本科讲座课程和一门高级生物学本科专业和研究生原核分子遗传学课程。与美国和印度的研究人员开展的合作促进了国际科学和文化交流。哈默博士还制定了一个推广计划，让不同种族的城市K-12学生参与刺激动手科学活动，这些活动将与在亚特兰大大都会地区教授代表性不足的少数民族学生的当地教育工作者分享。他是佐治亚理工学院和周边社区科学推广活动的志愿者，也是多家期刊的临时审稿人。他是一位活跃的教师和导师，目前有3名本科生和2名研究生，1名博士后研究员。

Intellectual Merit: The overall goal of this research is to understand the role of non-coding small RNAs (sRNAs) in controlling cellular processes in bacteria including survival in the environment. The bacterium, Vibrio cholerae, uses cell-cell communication, or quorum sensing (QS), to synchronously regulate expression of four Qrr RNAs (quorum regulatory RNAs) in response to the density of the bacterial population. Recent studies demonstrated that the Qrr sRNAs, like other bacterial sRNAs, can regulate multiple target genes. Although V. cholerae is a transient human pathogen, it is a common inhabitant of the aquatic estuarine and marine ecosystems. This research project is designed to exploit the understanding of the model V. cholerae QS system to discover the role of the Qrr sRNAs in influencing microbial behaviors in diverse environmental settings. Specifically, this project will address the following aims. Aim 1: To identify genes controlled by the quorum sensing-regulated sRNAs. Aim 2: To define the molecular mechanism of sRNA regulation using genetic, biochemical, and computational methods. Aim 3: To assess the conservation of QS circuitry and function in V. cholerae strains isolated from diverse locations. Because sRNAs are involved in important biological functions in all domains of life, defining the mechanism by which these sRNAs act will have fundamental implications for understanding regulatory circuitry of all cellular systems. Moreover, bacterial cell-cell communication systems are widespread in environmentally, commercially, and clinically significant microbes. An understanding of how these signaling pathways function, and how they control bacterial survival in the environment can ultimately engender strategies to curtail world-wide problems of environmental, human, animal and plant health. Broader Impacts: The applicant engages in teaching and service activities aimed at disseminating modern scientific discovery and fostering interactions between members of the academic community and broader society. Training of students includes teaching an undergraduate lecture course and a course for upper level undergraduate Biology majors and graduate students in Prokaryotic Molecular Genetics. Collaborations initiated with researchers within the United States and in India promote international scientific and cultural exchange. Dr. Hammer has also developed an outreach program to engage ethnically diverse urban K-12 students in stimulating hands-on scientific activities that will be shared with local educators who teach under-represented minority students in the metro-Atlanta area. He is a volunteer for science outreach events at Georgia Tech and in the surrounding community, an ad hoc reviewer for multiple journals. He is an active teacher and mentor currently of three undergraduate and two graduate students, and one postdoctoral researcher.