Tracking and tracing complex DNA structures critical to human health

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Rosalind Franklin's pioneering work to establish the atomic structure of DNA has underpinned much of our understanding of the 'molecule of life'. However the behaviour and function of complex genomic DNA is also heavily governed by its material characteristics i.e. shape and conformation. This complexity affects enzyme interactions, how cells age (and therefore aging of the human body) and can be a significant factor in pathologies such as cancer. The challenge of understanding exactly how shape and conformation in complex DNA nanostructures influences DNA interactions is fundamentally limited by the tools available. This project will apply our cutting edge single-molecule Atomic Force Microscopy (AFM) techniques to explore for the first time how complex DNA nanostructures form during replication in cancerous cells, and how anti-cancer therapeutics affect the structure and conformation of these DNA nanostructures, providing new insight into their mechanism-of-action. Given the emergence of replication stress inhibitors as therapeutic agents, and the increasing awareness of the biophysical forces that act on DNA to influence cell behaviour, this project is perfectly positioned to progress our understanding of complex DNA structures in cancer. By understanding this complexity, we can shed new light on how DNA in the cell behaves, and what factors are at play when things go wrong and how we can exploit this material for therapeutic gain.