Transcriptional Control of Early Development in Myxococcus Xanthus

智力上的优点：大多数微生物生活在“要么盛宴，要么饥荒”的环境中，在丰收的时候生长和繁殖，在贫困的时候生存下来。细胞在饥饿条件下生存的能力对种群的最终生存至关重要。因此，识别和了解微生物在饥饿条件下生存的机制对于了解细胞如何适应环境变化是至关重要的。粘杆菌是粘杆菌中最具特征的成员，它进化出了一种新的解决方案来解决这个要么盛宴要么饥荒的问题：发育的多细胞，其中一部分细胞分化成一种休眠的环境抵抗状态，称为粘孢子，并构建一种称为子实体的宏观结构。正是在子实体内，休眠的粘孢子持续存在，直到环境条件改变，有利于它们最终萌发，并重新建立群体。该项目的重点是确定黄曲霉用来监测和响应养分供应的遗传机制，并确定哪些营养限制条件触发细胞激活发育程序。具体地说，这项研究将确定启动这种复杂的发育反应所需的调控基因及其控制的途径。长期目标是构建一张详细的调控电路图，对饥饿诱导的发育程序中的遗传交互作用进行建模。这一调控图谱还将有助于理解粘菌多细胞发育的进化及其与其他发育微生物如芽孢杆菌、蓝藻和链霉菌的进化关系。更广泛的影响：这项研究的更广泛的影响主要是两方面的。首先，本研究将为粘细菌基因表达的饥饿激活提供基础信息。这很重要，因为它是在这个过程中？饥饿？包括粘细菌在内的许多微生物产生具有商业、农业和药理学重要意义的化合物和酶的时期。通过识别饥饿识别和发育启动的调节电路并对其进行建模，这些过程最终可以被设计成高效地生产具有生物重要性的化合物。目前，粘细菌是这类化合物的第三大细菌生产者，但仍是一种未得到充分研究和开发的资源，具有巨大的潜力。这项研究将产生可应用于工业界和学术界其他相关研究领域的材料、试剂和一般方法。其次，该项目将作为一个培训实验室，为毕业生、本科生和高中生提供培训，其中许多是女性和少数民族，他们将继续长期从事科学工作。在这个项目的过程中，高中生、本科生和研究生将接受最先进的研究方法和技术的培训。其中一个目标是在研究生的指导下，为本科生开发一门综合性课程。这一经历不仅将为研究生提供指导和教学方面的培训，还将为作为研究团队成员工作的本科生提供密集的独立研究经验。最终，这项研究项目将有助于培训下一代科学家，并通过增加我们对微生物生态学、基因调控机制及其进化以及天然产品生产的基本知识，使社会受益。

Intellectual Merit: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.