Transcription elongation is the process of synthesis of RNA on genomic DNA, and is a heavily regulated step of gene expression. Metabolic switches, life style choices, and virulence of bacteria are frequently regulated at the level of transcription elongation, which, not surprisingly, is a potent target for antibiotics. Malfunctions of transcription elongation in human cells are linked to various serious diseases, including cancers, Alzheimer, multiple sclerosis. Therefore, understanding the fundamental mechanisms of transcription elongation and its regulation is essential for intelligent manipulation of pathogenic and biotechnologically important microorganisms, development of new antibiotics and fighting diseases.
However, the molecular mechanisms of regulation of transcription elongation are poorly understood. The project will investigate the following aspects of transcription elongation (i) the mechanisms of transcription pausing and prevention of collisions of RNA polymerase with replication, (ii) influence of transcription elongation factors, small molecule effectors and metal ions on transcription fidelity and processivity, (iii) control of transcription elongation by coupled translation.
The project offers training in a wide range of biochemical, biophysical and microbiological techniques (see for example our papers: SCIENCE (2013), 340:1577-1580; NATURE CHEM BIOL (2013) 9:811-7; EMBOJ (2012) 31:630-9; EMBOJ (2011) 30:3766-75;). We will use unique experimental systems developed by the team, as well as novel methods based on next generation sequencing (such as NET-seq, ribosome profiling, etc.) and accompanying bioinformatics tools.
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. Furthermore, the project will be run in collaboration with DTP partner in the Biomolecular Interactions group at Durham University, which has combined expertise in cell biology of metals, and protein structure and function, with associated state of the art equipment.
The project will bring insights into fundamental aspects of regulation one of the most important processes in the cell, and will pave the way for development of new antimicrobials and understanding the basic mechanisms of diseases.
For further information see the website: http://www.ncl.ac.uk/camb/
Please submit a full CV and covering letter directly to [email protected]
This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,057 for 2015-16). The PhD will start in September 2016. 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.
Nielsen, S.U., Yuzenkova, Y., and Zenkin, N. (2013). Mechanism of RNA polymerase III transcription termination Science, 340: 1577-1580.