RNA metabolism and regulation in Streptomyces bacteria

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Non-coding RNAs are important mediators of cellular processes in all groups of organisms. The aim of this proposal is to understand the function and mechanism of sRNA activity in the Streptomyces bacteria. The streptomycetes are renowned for their metabolic diversity and morphological complexity, producing a vast array of metabolites with utility in medicine (human and veterinary) and agriculture, including herbicides, anti-cancer agents, and most known antibiotics. They are also multicellular organisms that differentiate to form distinct tissue types, providing an opportunity to study cell differentiation in a simple bacterial system. ******Leveraging the power of RNA-sequencing, we have assessed the sRNA potential of three evolutionarily divergent streptomycetes, and have defined a core group of 25 conserved sRNAs. We will characterize the biological function of select sRNAs, prioritizing those affecting development or metabolism. To identify sRNA regulatory targets, we will take a multi-dimensional approach, integrating in vivo affinity purification with transcriptomic and proteomic strategies. Mechanisms of action will be revealed using in vivo and in vitro sRNA-target interaction studies, and will be coupled with experiments aimed at exploring the role of ribonucleases in sRNA-mediated regulation, and their contributions to RNA metabolism in general. We will exploit our understanding of sRNA-mediated gene regulation to develop synthetic strategies aimed at the engineering and manipulation of Streptomyces regulatory networks. ******The long term objective of this research proposal is to define novel sRNA-regulatory pathways, and integrate these into known cascades governing morphological differentiation and metabolite production. This work will provide fundamental insights into Streptomyces biology, will reveal both universal themes in bacterial gene regulation and unique regulatory strategies, and will be highly relevant to the biotechnology industry.