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Centre for Stress and Age-Related Disease
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    • A computational protocol to model organophosphonate CWAs and their simulants
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  • Translational regulation of stress responses and antibiotic production in Streptomyces bacteria

Translational regulation of stress responses and antibiotic production in Streptomyces bacteria

We are focussing on understanding how Streptomyces bacteria respond to stress at the level of gene expression and how they control the gene clusters that encode production of so-called ‘secondary metabolites’, which include the majority of antibiotics in clinical use since the 1940s. We are exploiting genomics technologies within Brighton Genomics to understand, at a global level, how the system is regulated both at the level of transcription and translation.

Professor Smith is the lead organiser of a prestigious Royal Society International Scientific Meeting in March 2018 entitled ‘Changing views of translation: from ribosome profiling to high resolution imaging of single molecules in vivo’. This meeting brings together world leading researchers from across the world who study gene expression at two ends of the spectrum – from, on the one hand, global analysis of translation of all genes in cells and tissues to, on the other hand, analysis of expression of single molecules using new high resolution imaging techniques. It is hoped that the bringing together of scientists from these two fields could facilitate the development of new collaborations and approaches aimed at understanding how cellular processes are co-ordinated within cells.

Project timeframe

This project commenced in 2012 and is ongoing.

Project aims

The main aim of this research project is to understand how key genes are controlled at the level of translation in this complex group of soil bacteria. To date most studies of gene expression have focussed on studying transcription, the production of mRNAs. However, a new technique called ‘ribosome profiling’ (Ribo-seq) enables us to measure the level of translation of all mRNAs. This gives us a very different picture of gene expression and, importantly, reveals that the control of gene expression at the level of translation is far more widespread than we realised. Our goal is to determine the molecular processes which mediate this control by identifying the proteins and RNA molecules which co-ordinate the regulation. We currently know very little about how these processes function in bacteria.

 

 

Project findings and impact

We have discovered extensive translational control of key stress-response and antibiotic biosynthesis and resistance genes and can now start to investigate which proteins and RNA sequences govern control of these genes. 

This basic research should find applications in the biotechnology industry through assisting the antibiotic discovery pipeline and for improving antibiotic production processes. This will lead to societal and economic benefits because there is an urgent demand to develop new antibiotics to combat antibiotic resistant bacterial infections and to address the increased demand for existing antibiotics by the pharmaceutical industry.

Research Team

Prof Colin P. Smith

Dr Giselda Bucca

Dr Andy Hesketh

Output

Bucca G, Pothi R, Hesketh A, Moller-Levet C, Hodgson DA, Laing EE, Stewart GR, Smith CP (2017) Translational control plays an important role in the adaptive heat-shock response of Streptomyces coelicolor. bioRxiv 223925; 

doi:  doi.org/10.1101/223925.

Jeong Y, Kim J-N, Kim MW, Bucca G, Cho S, Yoon YJ, Kim B-G, Roe J-H, Kim SC, Smith CP, Cho B-K (2016) The dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2). Nature Communications, 7: 11605
www.nature.com/articles/ncomms11605

Partners

GlaxoSmithKline, Worthing, UK

 Prof Byung-Kwan Cho, Korea Advanced Institute of Science and Technology (KAIST), South Korea

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