Congratulation to LCN researcher, Dr Alice Pyne, who has been awarded a prestigious MRC UKRI Innovation/Rutherford Fellowship.
This exciting new fellowship program aims to create the future for international leaders in research. The Fellowships form part of the recent government investment to the MRC from the National Productivity Investment Fund.
Dr Pyne’s expertise is in high resolution single studies of DNA structure. She has achieved unprecedented resolution for single biomolecules in solution through the development of new Atomic Force Microscopy probes and techniques in collaboration with Bruker (CA, USA). Her research has resulted in both the highest-quality Atomic Force Microscopy images of the DNA double helix achieved to date, and the first visualisation of variations in the DNA double helix structure on a single molecule (Pyne et al., Small, 2014). More recently, Dr Pyne has exploited these techniques to visualise quadruplex formation in DNA minicircles, as part of a study characterising the role of DNA topology in evaluating quadruplex stabilising molecules: a possible class of anticancer therapeutics (Klejevskaja*, Pyne* et al., Chem. Comm, 2016).
During her MRC UKRI Innovation/Rutherford Fellowship, Dr Pyne aims to improve our understanding of how topoisomerases untwist DNA, and how this is prevented by topoisomerase inhibitors, to aid in the development of new or improved anticancer drugs and antibiotics.
Topoisomerases are enzymes, present in all organisms from humans to bacteria, which are essential for life due to their ability to untangle knotted and twisted DNA. The knotting and twisting of our DNA occurs as two metres of our DNA is folded into the cell nucleus; much narrower than the width of a human hair. This is exacerbated by the molecular machinery in our cells which travel along our DNA pulling it apart and manipulating it in a compact environment. Without topoisomerases, our DNA becomes irreversibly knotted and twisted and the cell will die. For this reason, key therapeutics such as anticancer and antibiotic drugs target human and bacterial topoisomerases respectively either killing cancerous or bacterial cells.
Dr Pyne’s work will provide insight into how topoisomerases are able to untwist DNA, and how this process can be disrupted by drugs. Her research aims to contribute to our understand topoisomerase-DNA interactions by collaborating with Prof Anthony Maxwell at the John Innes Centre. Dr Pyne’s work will also utilise single molecule techniques including Atomic Force Microscopy, and magnetic tweezers, in partnership with Bruker (Santa Barbara, CA, USA) and Dr Justin Molloy at The Francis Crick Institute.