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Structure and functions of the novel type of RNA polymerases and their application in synthetic biology and biotechnology


   Biosciences Institute

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  Prof N Zenkin, Prof Ehmke Pohl  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

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) YONO-RNAPs are encoded by completely unexplored bacteriophages of many clinically, industrially and agriculturally important bacteria (various Bacilli, Clostridia, 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 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 papers: Molecular Cell (2018) 72:263; Nature Communications (2017) 8:15774; 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. 

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with:

·      a CV (including contact details of at least two academic (or other relevant) referees);

·       a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;

·      copies of your relevant undergraduate degree transcripts and certificates;

·      a copy of your IELTS or TOEFL English language certificate (where required);

·      a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed]

The deadline for all applications is 12noon on Monday 9th January 2023. 


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

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
Stevenson-Jones, F., Woodgate, J., Castro-Roa, D, Zenkin, N*. (2020) Ribosome reactivates transcription by physically pushing RNA polymerase out of transcription arrest. PNAS 17:8462-8467.
Harbottle J, Zenkin N*. (2020) Ureidothiophene inhibits interaction of bacterial RNA polymerase with -10 promotor element. NUCLEIC ACIDS RES. 48(14):7914-7923.
Mosaei H., Molodtsov, V., Kepplinger B., Harbottle J., Moon C., Jeeves R., Ceccaroni L., Shin, Y., Morton-Laing S., Marrs M., Wills C., Clegg W., Yuzenkova Y., Perry J., Bacon J., Errington J., Allenby N., Hall M., Murakami K., Zenkin N*. (2018) Mode of Action of Kanglemycin A, an Ansamycin Natural Product that Is Active against Rifampicin-Resistant Mycobacterium tuberculosis. MOLECULAR CELL 72(2):263
Nielsen, S., and Zenkin, N*. (2013). Mechanism of RNA polymerase III transcription termination. SCIENCE, 340: 1577-1580.
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