Structure-function studies of the bacterial plasmid defence system Wadjet
Microbes are under constant attack from bacteriophages and other selfish genetic elements and have evolved a wide range of defence mechanisms. These include the well-known and influential restriction enzymes and CRISPR-Cas, which have been exploited for molecular biology and gene editing, respectively. Yet there are many other uncharacterised systems within genomic defence islands that may provide yet more tools for scientists. This project aims to use biophysical analysis and structural biology to explore the mechanism of one such system, named after the Egyptian goddess Wadjet. Wadjet prevents transformation by plasmids, so will influence horizontal gene transfer and the acquisition of traits such as virulence or antibiotic resistance.
Wadjet comprises four genes: jetA, jetB, JetC and JetD. jetABC encode gene products that are related to the microbial condensins. Condensins are widespread across all organisms, and are ATP-dependent molecular machines that help regulate genome segregation during cell division. They form large protein complexes that use ATP hydrolysis to drive large-scale changes in DNA conformation, including tethering DNA together, or actively extruding DNA loops as molecular motors. However, their exact mechanisms and roles are still being debated. In this collaborative project between the Szczelkun and Berger-Schaffitzel labs at Bristol Biochemistry, you will determine the overall structure of the Wadjet complex, show how it interacts with DNA, and determine the role(s) for ATP hydrolysis using a combination of biochemical and single-molecule magnetic tweezers assays.
The SWBio DTP is one of the 12 Doctoral Training Partnerships funded by the BBSRC to provide PhD training in areas of their strategic relevance. The SWBio DTP is a consortium comprising the Universities of Bristol (lead), Bath, Cardiff, Exeter, and Rothamsted Research. Together, these institutions present a distinctive cadre of bioscience research staff and students with established international, national and regional networks and widely recognised research excellence.
For further details about the programme please see https://www.swbio.ac.uk/