Victoria Hill

The Conformational Dynamics of Two-Way DNA Junctions: A common first step in aberrant DNA recognition?

About me

I completed my MChem degree at Newcastle University in Medicinal Chemistry and undertook research under Dr Agnieszka Bronowska. This involved using molecular dynamics simulations to look at protein conformational dynamics and drug binding in DDi1. DDi1 is a protein with the potential to improve the effectiveness of proteasome inhibitor cancer chemotherapeutics. This was where I learnt some of the theoretical techniques that I now use in my PhD research and developed an interest in the conformational dynamics of biologically-relevant systems. My current project involves the use of biophysical experimental methods that I have not used previously, and so I am excited to learn these new techniques and integrate the experimental results within the theoretical models.

My project

I am studying under Dr Tim Craggs in the Department of Chemistry at Sheffield with the help of collaborators at the universities of Sheffield, York, and farther afield. I am using molecular dynamics simulations to complement single-molecule FRET and other biophysical methods for research into DNA damage and supercoiling conformational dynamics. To do this, I am using DNA minicircles as a model as they are the same size as the DNA loops commonly found in the body. Supercoiling is the untwisting of DNA, and it forms plectoneme loops to relieve the stress resulting from the untwisting. It is thought that damaged sequences within DNA are located at the tips of plectonemes in order to facilitate recognition by the various proteins involved in damage detection. A combination of the theoretical and experimental methods I will use should test this hypothesis and provide an insight into damaged DNA dynamics and interactions. In addition to this, I will use theoretical methods to produce better models for smFRET experiments and test the validity of the assumptions commonly made by researchers in this area.