Regulatory networks controlling differentiation in streptomyces coelicolor

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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.