Most microbes live in a "feast-or-famine" environment, growing and reproducing in times of plenty and surviving the lean times. The ability of a cell to survive starvation conditions is crucial to the ultimate survival of the population. Therefore, identifying and understanding the mechanisms used by microbes to survive under starvation conditions is essential for understanding how cells adapt to environmental change. The Myxobacteria, of which M. xanthus is the best characterized member, has evolved a novel solution to this feast-or-famine problem; developmental multicellularity, where a subset of cells differentiate into a dormant environmentally resistant state called a myxospore and constructing a macroscopic structure called a fruiting body. It is inside the fruiting body where the dormant myxospores persist until environmental conditions change to favor their eventual germination, and the reestablishment of the colony. This project focuses on identifying those genetic mechanisms used by M. xanthus to monitor and respond to nutrient availability and to determine which nutrient limiting conditions trigger cells to activate the developmental program. Specifically, this research will identify the regulatory genes required for the initiation of this complex developmental response as well as the pathways they control. The long term goal is to construct a detailed regulatory circuitry map that models the genetic interactions dsecribing the starvation-induced developmental program. This regulatory map will also aid in understanding the evolution of multicellular development in the Myxobacteria and its evolutionary relationship to other developmental microbes such as Bacillus, Cyanobacteria and Streptomyces.
Broader Impacts: The broader impacts of this research are primarily two-fold. First, this research will provide basic information on starvation-activation of gene expression in Myxobacteria. This is important because it is during this ?starvation? period that many microbes, including the Myxobacteria, produce compounds and enzymes of commercial, agricultural and pharmacological importance. By identifying and modeling the regulatory circuitry of starvation recognition and development initiation, these processes can eventually be engineered to efficiently produce biologically important compounds. Currently the Myxobacteria represent the third largest bacterial producers of such compounds and yet remain an understudied and under-tapped resource of great potential. This research will produce materials, reagents and general methods that can be applied to other related research areas in both industry and academia. Second, this project will serve as a training laboratory to graduate, undergraduate and high school students, many of whom are women and minorities who will continue with long-term careers in science. During the course of this project, high school, undergraduate, and graduate students will receive training in state-of-the-art research methods and techniques. One objective is to develop an integrative course for undergraduates under the guidance of graduate students. This experience will not only provide training in mentoring and teaching to graduate students, but will also provide an intensive independent research experience for undergraduates working as members of a research team. In the end, this research project will benefit society by aiding in the training of the next generation of scientists and by increasing our basic knowledge of microbial ecology, genetic regulatory mechanisms and their evolution, and natural product production.
