Transcribing Success: Characterising the Factor Behind Bacterial Development and Antibiotic Production
Over 50% of the antibiotics used in medicine are produced by Streptomyces bacteria. The production of antibiotics is intertwined with the Streptomyces lifecycle and controlled by diverse transcriptional regulators, including regulators of the poorly understood Wbl-protein family.
We recently discovered that the overproduction of an uncharacterised transcriptional regulator of the Wbl family affects cellular development and antibiotic production in Streptomyces. Our preliminary data suggest that this regulator binds to specific genomic regions across the Streptomyces chromosome, indicating that it has a broad regulatory impact.
We are now looking for a motivated PhD student to unravel the regulatory network that underpins the function of this Wbl regulator in Streptomyces development and antibiotic production. Specifically, this project aims to (1) Characterise the regulon of the Wbl transcription factor and define its genome-wide target promoters; (2) Investigate its role in vivo to identify protein partners and understand its impact on Streptomyces antibiotic production and development; and (3) Discover novel antibiotics produced in response to the transcriptional activation by the Wbl-regulator.
The outcomes of this work will provide novel insights into the biology of Streptomyces and the regulation of antibiotic biosynthesis, which has the potential to aid the discovery and production of important medical and industrial molecules.
The project offers multidisciplinary training, including molecular microbiology, global gene regulation analyses, protein-protein interaction studies, and the characterisation of novel bioactive molecules. This will provide you with highly transferrable skills and a wide choice of career options in academia and industry.
You will be based in the laboratory of Dr Susan Schlimpert (www.schlimpert-lab.com) in the Department of Molecular Microbiology at the John Innes Centre, which is a world-class institute for Streptomyces research.
Applications are welcomed from students across the biological sciences who desire to work on a multidisciplinary project. Informal enquiries to susan.schlimpert@jic.ac.uk are welcome.
References
Schlimpert, S. & Elliot, M. A. The Best of Both Worlds – Streptomyces coelicolor and Streptomyces venezuelae as Model Species for Studying Antibiotic Production and Bacterial Multicellular Development. J Bacteriol 205, e0015323 (2023).
Stratton KJ, Bush MJ, Chandra G, Stevenson CEM, Findlay KC, Schlimpert S. Genome-Wide Identification of the LexA-Mediated DNA Damage Response in Streptomyces venezuelae. J Bacteriol. 2022 Aug 16;204(8):e0010822. doi: 10.1128/jb.00108-22. Epub 2022 Jul 13. PMID: 35862789; PMCID: PMC9380542.
Bush, M. J., Gallagher, K. A., Chandra, G., Findlay, K. C. & Schlimpert, S. Hyphal compartmentalization and sporulation in Streptomyces require the conserved cell division protein SepX. Nat Commun 13, 71 (2022).
Bush MJ. The actinobacterial WhiB-like (Wbl) family of transcription factors. Mol Microbiol. 2018 Dec;110(5):663-676. doi: 10.1111/mmi.14117. Epub 2018 Oct 25. PMID: 30179278; PMCID: PMC6282962.