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PhD project

My PhD project is titled "Analyses and exploitation of AHFCA-dependent signalling systems in Streptomyces bacteria".

Based in School of Life Sciences and Chemical Biology Research Facility, Department of Chemistry.

Supervised by Dr. Christophe Corre and Dr. Jay Moore.

Background

Streptomyces forms the largest genus of Actinobacteria and are notable for their medicinal and pharmaceutical significance as they produce a wide variety of useful secondary metabolites including two-thirds of today's clinically approved antibiotics [1, 2].

Since the sequencing of several Actinomycetes, a large number of gene-clusters proposed to be involved in the biosynthesis of secondary metabolites have been identified through bioinformatics analyses [3]. However, some of these secondary metabolite gene clusters are not normally expressed in laboratory conditions [3] and are tightly regulated at the transcriptional level.

ArpA-like transcriptional repressor proteins are involved in the complex signalling cascade to turn on the expression of secondary metabolite gene cluster [4]. To date, predictions to the precise biological roles of these ArpA-like transcriptional repressors and where they interact is extremely challanging. Understanding the complex regulatory mechanisms would provide strategies to discover novel drug-like compounds.

Aims of the project

The analyses of AHFCA-dependant signalling systems involved in controlling specialised metabolite biosynthetic gene clusters and to exploit these regulatory systems in Streptomyces bacteria to discover products of cryptic biosynthetic gene clusters.

References

[1] Kieser, T. et al. "Practical Streptomyces Genetics". 2000, Norwich, John Innes Foundation; [2] Hopwood, D. A."Streptomyces in Nature and Medicine: The Antibiotic Makers". 2007, New York, Oxford University Press; [3] Challis, G. L. 2008, Microbiology. 154 (6), 1555 - 1569; [4] O'Rourke, S. et al. 2009, Mol. Microbiol., 71 (3), 763-778;