Regulation of transcription in Streptomyces coelicolor

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My defining interest is how transcription is controlled in S. coelicolor in vivo and the translation of the research to generate tools capable of controlling bacterial gene expression. My bias is to take a biochemical approach by studying DNA-protein interactions: both between transcription factors and regulatory sequences and also of the chromatin/nucleoid-proteins within genes or genomic domains. The competitive advantage of this work is that we would be first to adapt a suite of powerful and informative eukaryotic techniques to prokaryotes. Predicted outcomes from this work include: new knowledge of a predecessor of eukaryotic chromatin; the development of a model system for biochemical analysis of chromatin more tractable than eukaryotic ones; the creation of a technology platform capable of controlling bacterial gene expression, with implications for engineering of microbial strains for industrial biotechnology and also as novel therapies to treat infection; fresh insights into how to manipulate bacterial secondary metabolism.
Hence, there are two main themes. Firstly, a study of epigenetic regulation of secondary metabolism as early evidence has shown that something akin to chromatin-structure exists in S. coelicolor and affects expression of secondary metabolic genes. Can these insights be used to derepress ‘cryptic’ pathways in exotic actinomycetes to discover new chemical diversity? Secondly the development of ‘Nucleoproteomics’- specifically using Transcription Factor Decoys (TFDs) as a genomic tool to map DNA-protein interactions. The aim being to develop a complimentary technology to transcriptomic microarray analysis that provides information about the DNA-protein interactions that control patterns of expression. One of the unique features of this approach would be determining how in vivo post-translational modificiation of transcription factors affect expression.

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