Regulatory networks controlling differentiation in streptomyces coelicolor

链霉菌是一类广泛存在的丝状细菌，在土壤生态学中发挥重要作用，产生重要的生物活性物质，并作为微生物分化的模式系统而被广泛研究。链霉菌能够在陆地生态系统中分泌或降解多种化合物。每个物种通常编码自己的200多种酶，这些酶能够解毒和回收土壤中植物，动物和其他微生物的废弃物和死亡物质。它们是抗生素以及其他代谢物的最丰富的已知来源，其具有作为除草剂、抗癌药物、免疫调节剂和抗寄生虫化合物的应用。酶和生物活性化合物的分泌与形态发育程序相协调。经过一段时间的菌落生长，细菌链生长到空气中，然后变成一种不活跃的抵抗形式，称为孢子。拟议的研究计划旨在阐明调控天蓝色链霉菌发育的网络和机制。 我们将使用新的基因组序列信息和遗传技术来分析基因表达的全球模式。荧光显微镜将用于定位殖民地或细胞中的蛋白质。通过首先表征野生型菌株，我们将捕获发育程序背后的基因表达模式。我们以前的研究表明，发育程序是由少数关键调控基因控制的。因此，我们将比较野生型与工程菌株的表达模式，以激活或抑制这些基因。一种迭代方法将提供信息，以绘制监管网络。最后，探讨基因活化的分子机制。我们的研究将首先集中在形态发生的变化，导致孢子的形成，扩展我们以前的研究殖民形态发生的中央调节器（ramR基因）。总的来说，这些研究将为微生物分子生物学和土壤生态学提供基本的见解。从长远来看，这项研究也将促进新的化疗药物的发现和工程。

Streptomyces are a ubiquitous group of filamentous bacteria that play important roles in soil ecology, produce important bioactive compounds, and have been widely studied as a model system for microbial differentiation. Streptomyces species are able to secrete or degrade diverse compounds in terrestrial ecosystems. Each species typically encodes its own collection of more than 200 enzymes able to detoxify and recycle discarded and dead material from plants, animals, and other microorganisms in the soil. They are the most prolific known source of antibiotics as well as other metabolites having applications as herbicides, anticancer drugs, immunoregulators, and antiparasitic compounds. Secretion of enzymes and bioactive compounds is coordinated with a program of morphological development. Following a period of colonial growth, chains of bacteria grow up into the air and then change into an inactive, resistant form called a spore. The proposed research program seeks to elucidate the network and mechanisms that regulate the development of Streptomyces coelicolor.  We will use new genome sequence information and genetic technologies to analyze the global patterns of gene expression underlying development. Fluorescence microscopy will be used to locate proteins in the colony or cell. By first characterizing the wild type strain, we will capture the patterns of gene expression underlying the developmental program. Our previous studies have shown that developmental programs are controlled by a small number of key regulatory genes. We will therefore compare expression patterns in the wild type with strains engineered to activate or inactivate these genes. An iterative approach will provide information to map the regulatory network. Finally, the molecular mechanism of gene activation will be explored. Our studies will initially focus on morphogenic changes leading to spore formation, extending our previous studies of a central regulator of colonial morphogenesis (the ramR gene). Overall, these studies will provide fundamental insights into microbial molecular biology and soil ecology. In the long term, this research will also facilitate the discovery and engineering of novel chemotherapeutic drugs.