Location location location – how genome position affects gene expression WEBBER_Q22DTP

Applications Close: 11 July 2022

Bacterial genomes have evolved over billions of year to allow efficient expression of the right genes at the right times and this is a carefully controlled process. It has recently become clear that the immediate genetic context of a gene is very important in determining how easily it is expressed. Experiments have shown that the same gene with the same promoter, placed in different locations around a bacterial chromosome can display very different levels of expression. The rules which govern this higher level if control of gene expression are not fully understood. This project aims to examine how position within a genome can affect gene expression, this will help us both understand how genomes work and evolve, and use this information to rationally design synthetic chromosomes to deliver optimised expression of important genes used in bioprocessing etc.

The project will compare expression of millions of copies of the same gene promoters placed in different locations in both Salmonella and E. coli – two related species which share some genome organisation but control gene expression differently. The project will make use of tools already developed to allow expression to be measured under different conditions, and will involve a mix of molecular microbiology, transcriptomics and informatics.

The student will join a large community of molecular microbiologists within the Quadram Institute in a brand new, purpose built building with state of the art facilities. The Quadram Institute is based on the Norwich Research Park – home to one of the largest groups of microbiologists in Europe and the student will join a large cohort of graduate researchers with exceptional training opportunities.

Informal enquiries can be sent to mark.webber@quadram.ac.uk

References

Webber MA, Ricci V, Whitehead R, Patel M, Fookes M, Ivens A, Piddock LJ. Clinically relevant mutant DNA gyrase alters supercoiling, changes the transcriptome, and confers multidrug resistance. mBio. 2013 Jul 23;4(4):e00273-13. doi: 10.1128/mBio.00273-13.

Page AJ, Ainsworth EV, Langridge GC. Socru: typing of genome-level order and orientation around ribosomal operons in bacteria. Microb Genom. 2020 Jul;6(7):mgen000396. doi: 10.1099/mgen.0.000396.

Yasir M, Turner AK, Bastkowski S, Baker D, Page AJ, Telatin A, Phan MD, Monahan L, Savva GM, Darling A, Webber MA, Charles IG. TraDIS-Xpress: a high-resolution whole-genome assay identifies novel mechanisms of triclosan action and resistance. Genome Res. 2020 Feb;30(2):239-249. doi: 10.1101/gr.254391.119.

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