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

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. 

Informal enquiries may be made to n.zenkin@ncl.ac.uk

HOW TO APPLY

Applications should be made by emailing bbsrcdtp@liverpool.ac.uk with a CV and a covering letter, 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. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Application Details Form (Word document) to bbsrcdtp@liverpool.ac.uk, noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.