To survive in a competitive environment a bacterium must be biologically fit. This is as important for free-living microbes that have to compete for limited nutrients in their habitat, as it is for pathogens who have to strike a fine balance between their own proliferation and evading detection by the host, or counteracting antibiotic exposure. On a grand scale, regulatory proteins allow bacteria to dramatically overhaul gene expression patterns in response to changes in conditions. However, as with any highly sophisticated engine, it is the fine-tuning that can really decide the race. In this PhD project, you will investigate one of the key molecular mechanisms, small regulatory RNAs (sRNAs), that allow bacteria to fine-tune their physiology and optimally adapt to conditions.
The explosion of Next-Generation Sequencing projects has highlighted the importance of post-transcriptional regulation, including sRNAs, in controlling bacterial survival. Most of these studies have focussed on Gram-negative bacteria, like E. coli. However, we understand far less about how Gram-positive bacteria, such as Staphylococcus, Streptococcus and Bacillus species employ sRNAs to micro-manage their physiology. This project will build on extensive prior work by the Denham lab, which has led to the identification of an sRNA ‘hub’ in this group of bacteria. This hub consists of at least three different sRNAs, and is involved in controlling competitive fitness, biofilm formation, antimicrobial production and antibiotic resistance. As the successful candidate, you will take our research to the next level by addressing the following questions:
(1) What are key players that enable the sRNA hub to function?
(2) How are its components regulated?
(3) How does RNA processing affect the function of the hub?
(4) How does the hub control bacterial physiology?
Under the guidance of an interdisciplinary team of researchers, you will receive training in cutting-edge molecular biology and microbial physiology, combined with bioinformatics analyses of ‘omics’ data. The project is part of an international collaboration with the Condon/Durand lab in Paris, providing opportunities for exchange of expertise with world-leading experts in the field, and equipping you for a successful career in science.
Applicants should hold, or expect to receive, a First Class or high Upper Second Class UK Honours degree (or the equivalent qualification gained outside the UK) in a relevant subject. A master’s level qualification would also be advantageous.
Informal enquiries should be directed to Dr Emma Denham, [email protected]
Formal applications should be made via the University of Bath’s online application form: https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-FP02&code2=0013
Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section. Should you wish to apply for more than one advertised project, you should submit a separate personal statement for each one.
More information about applying for a PhD at Bath may be found here: http://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/
Anticipated start date: 30 September 2019.
Mars RA, Nicolas P, Ciccolini M, Reilman E, Reder A, Schaffer M, Mader U, Volker U, van Dijl JM, Denham EL: Small regulatory RNA-induced growth rate heterogeneity of Bacillus subtilis. PLoS Genet 2015, 11:e1005046.
Mars RA, Nicolas P, Denham EL, van Dijl JM: Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression. Microbiol Mol Biol Rev 2016, 80:1029-1057.
Nicolas P, Mader U, Dervyn E, Rochat T, Leduc A, Pigeonneau N, Bidnenko E, Marchadier E, Hoebeke M, Aymerich S, et al: Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. Science 2012, 335:1103-1106.