An interview with Dr Emma Denham
Dr Emma Denham is a Senior Lecturer at the University of Bath, and a member of the Microbiology Society. In this interview, she tells us more about her research which focuses on studying gene regulation in bacteria, and how, with the use of cutting-edge RNA-sequencing techniques and molecular biology, she is helping to identify the interacting partners of sRNAs.
Why is studying gene regulation in bacteria important?
Bacteria are remarkable. As single cells, they are able to survive changing conditions and onslaughts from the environment in which they find themselves, whether this is due to changes in nutrient availability, exposure to antibiotics, competition with other bacteria, or attacks from the immune system. Each condition requires the expression of different genes. Bacteria have regulatory mechanisms to ensure that genes are switched on and off when conditions demand it.
Historically, research on the environmental bacteria Bacillus subtilis has revealed many details about how bacteria monitor and respond to their environment, through regulation of transcription using combinations of the multitude of condition-dependent sigma and transcription factors. The high genetic manipulability and its role as a simple developmental model has placed B. subtilis as a model system. Bacillus species are also key organisms for the industrial production of many important molecules.
How is your lab advancing our understanding of gene regulation?The invention of post-genomic technologies such as RNA-sequencing (RNA-seq) has revealed that genomes have much more transcriptional activity than we first imagined. The research in my laboratory is focused on resolving the role of this so called ‘non-coding RNA’ in relation to environmental changes.
Small RNAs function by pairing with other RNAs to affect their rate of translation or degradation, therefore changing the level of the protein in which they encode. The control of transcription that bacteria have, allows the overhaul of the transcriptional landscape to be made. However, regulation with sRNAs enables small quick changes that give bacteria a fitness benefit over neighbouring cells.
We use cutting edge RNA-sequencing techniques and molecular biology to identify the interacting partners of sRNAs. This has not only enabled us to identify classic mRNA-sRNA interacting partners, but also more novel interactions such as sRNA-sRNA pairings. The interaction of two sRNAs adds an additional level of control of sRNA regulons. Bacteria have preferential orders in which they use nutrition and evolved systems to ensure they are optimally used. The absence of the sRNA-sRNA interaction results in the bacteria being less fit and unable to correctly regulate the enzymes that act in metabolism under specific growth conditions.
Unlike protein drug targets that are often highly conserved, sRNAs are specific to individual bacterial species and therefore offer new lines of research for alternative antimicrobials.