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The sRNA interactome of Bacillus subtilis


Project Description

The identification of non-coding RNA transcripts from Next-Generation Sequencing projects has highlighted the importance of post-transcriptional regulation in bacterial survival. High interest in this area of study has highlighted the large number of different processes that are affected by post-transcriptional regulation, these include bacterial metabolism, antibiotic resistance and developmental processes. The field has been dominated by studies in members of the Enterobacteriacae, due to their requirement of the RNA chaperone protein Hfq. The genome of the model Gram-positive bacterium Bacillus subtilis is the most well annotated of all bacteria with over 1500 RNAs, including 150 sRNAs being expressed in over 104 different conditions (Nicolas et al, Mars et al). To date, very few of these RNAs have been given a function within the cell. However, where a function has been identified, they have been shown to have roles in bacterial growth and survival (Mars et al). sRNAs are the class of non-coding RNA where the widest variation of expression is seen. Different sRNAs are regulated by all the different sigma factors, including those involved in sporulation and resistance to antibiotics.

The Project:

The lack of a known RNA binding protein playing a role in any of the known sRNA-target interactions has hampered identification of sRNA function. Therefore, we have used a cutting edge global in vivo RNA interaction study to identify new RNA-RNA interactions. Within the data we have identified thousands of RNA-RNA interactions. This includes the two sRNAs FsrA and RoxS, where several targets have been previously identified. We found not only these already established targets, but also new targets that suggest other functions for these sRNAs - including in biofilm formation. Within the data we have also identified sRNA-sRNA and mRNA-mRNA interactions, which hint at new mechanisms of RNA regulation to be explored. We have focussed our studies to date on one sRNA-sRNA interaction that has shown several novel mechanisms of post-transcriptional regulation, including processing with an as yet unidentified RNase.

This project will combine generation and analysis of RNA interactome datasets (for example biofilm development, stress conditions and sporulation) and molecular characterization of specific post-transcriptional regulatory events. This will expand the repertoire of sRNAs with known functions and increase our understanding of the mechanism(s) of post-transcriptional regulation in Gram-positive bacteria.

Candidate:

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.

Applications:

Informal enquiries should be directed to Dr Emma Denham,

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.

Funding Notes

Candidates may be considered for a University Research Studentship which will cover UK/EU tuition fees, a training support fee of £1,000 per annum and a tax-free maintenance allowance at the UKRI Doctoral Stipend rate (£14,777 in 2018-19) for a period of up to 3.5 years.

References

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.

How good is research at University of Bath in Biological Sciences?

FTE Category A staff submitted: 24.50

Research output data provided by the Research Excellence Framework (REF)

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