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Novel RNA polymerases, and insights into molecular biology of agricultural, biotechnological and pathogenic bacteria containing them

  • Full or part time
  • Application Deadline
    Friday, January 11, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

In synthetic biology and biotechnology, there is an urgent need for alternative orthologous expression platforms for protein and RNA production and building complex synthetic networks. The existing systems based on single-subunit RNA polymerases (RNAPs) of T7 bacteriophage-type have limited capacity and applications.

Very recently we have discovered a new type of RNAPs – YONO-RNAPs (2017; Nature communications 8:15774). These small single-subunit RNAPs are not related to any known single-subunit RNAPs, and use previously unknown mechanisms of transcription and its regulation. Being a new paradigm in the mechanisms of transcription, YONO-RNAPs may become a new much needed tool for molecular/synthetic biology and biotechnology. Our research already attracted interest from biotech companies.

The programme of work consists of fundamental and translational aims: to determine the mechanisms of transcription and the structure of this new type of RNAPs, understand their roles in their bacteriophage/bacterial hosts, and to develop YONO-RNAPs-based orthologous gene expression systems. The proposed work will have potential impacts in molecular biology, evolution, biotechnology and health:
(i) Biochemical and structural characterisation of YONO-RNAPs promises discovery of novel mechanisms of transcription and its regulation.
(ii) The work promises delivery of much needed new molecular tools for molecular/synthetic biology and biotechnology applications.
(iii) Bacteriophages are widely used to fight pathogenic bacteria. YONO-RNAPs are encoded by completely unexplored bacteriophages of many agriculturally, clinically and industrially important bacteria (Clostridia, Bacilli and cyanobacteria); the proposed research will provide information about biology of these bacteriophages, which may help intelligent manipulation of their important bacterial hosts.

The project offers training in a wide range of biochemical, molecular biology, genetics and structural biology techniques as well as novel methods based on next generation sequencing and accompanying bioinformatics tools (see for example our recent papers: Molecular Cell (2018) 72:263; Nature Communications (2017) 8:15774; Nucleic Acids Res (2016) 44:2577; Nature Chem Biol (2013) 9:811; Science (2013) 340:1577). The project will be based in the Centre for Bacterial Cell Biology of Newcastle University, which brings together leading scientists in the field of biology of bacterial cell. The Centre is situated in the new building fitted with the state of the art equipment, and provides unique scientific environment.

For further information see the website: https://www.ncl.ac.uk/camb

To apply

Please complete the online application form and attach a full CV and covering letter. Informal enquiries may be made to

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,777 for 2018-19). The PhD will start in October 2019. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. There are 2 stages to the application process.

References

Forrest, D., James, K., Yuzenkova, Y., Zenkin, N. (2017) Single-peptide DNA-dependent RNA polymerase homologous to multi-subunit RNA polymerase. Nature Communications 8:15774. doi: 10.1038/ncomms15774.

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