Project Outline

In all lifeforms DNA is transcribed to create RNA templates for protein synthesis. This is known as the central dogma of molecular biology. Transcription is stimulated by regions of DNA called promoters. It has long been assumed that promoters drive transcription in one direction only. It seems illogical that promoters might simultaneously drive transcription “in reverse”. However, this phenomenon was reported for mammalian cells in 2008. Using genome-scale approaches, these studies concluded that mammalian promoters are inherently bi-directional; antisense and mRNA typically originate from the same region of DNA. This remarkable observation was met with some scepticism and any role remains a puzzle. In the intervening years, it has been assumed that the same does not happen in prokaryotic cells. However, in our recent work we have shown that bi-directional promoters are common in all prokaryotes (1). In this project, you will work on understanding what the role of bi-directional promoters is, how they work, and how they are regulated. Your research will involve the use of genetic, biochemical, genomic and bioinformatics tools.

References

Warman EA, Forrest D, Guest T, Haycocks JJRJ, Wade JT, Grainger DC (2021) Widespread divergent transcription from bacterial and archaeal promoters is a consequence of DNA-sequence symmetry. Nat Microbiol. 6(6):746-756

Techniques

Protein purification, Chromatin Immunoprecipitation, Illuminia Sequencing and associated bioinformatics, PCR, Radioisotopes, Microscopy, In vitro DNA binding assays, Reporter assays, Microbial cell culture, mutagenesis, lab based evolution