Victoria aims to further the understanding of how type II topoisomerases are regulated, and the use of metal ions during DNA cleavage.
Type II topoisomerases are regulators of DNA topology, making double stranded DNA breaks and controlling the movement of DNA through the break point. This allows essential biological processes to proceed, such as DNA replication and translation.
My PhD is titled ‘Structural and mechanistic analysis of type II DNA topoisomerases’. A key focus will be looking at the motion of the metal ion, proving, or disproving the controversial moving metal hypothesis.
To investigate this hypothesis Victoria will use two main approaches: Using enzymology, to look at the effects of different metals, mutants, organisms and antibiotics on the cleavage and religation of DNA; and a structural biology approach using X-ray crystallography. By visualising the enzyme complexed with DNA and heavy metals, combined with the use of time-resolved crystallography Victoria aims to capture intermediates during cleavage and religation.
Combined, these tools will help answer questions in the mechanisms of topoisomerase type II. Understanding the enzymes action is important due to their relevance as targets for anti-bacterial and anti-tumour drugs.