Dr John Fielden, Reader and Head of the Inorganic Chemistry Section in the LU chemistry, has started the project “Probing for i-Motif DNA with Ruthenium Complexes”, with the arrival of Senior Research Associate Dr James Williams. The project, supported by a £307k Leverhulme Trust Research Project Grant, is in collaboration with Professor Zoë Waller (UCL Pharmacy), an expert in DNA-small molecule interactions. It aims to develop small-molecule metal complexes capable of in-cell detection of i-Motif – a form of DNA whose biological role is still poorly understood, but has links to gene expression and diseases including diabetes and cancer.

The famous Watson-Crick “twisted ladder” double helix is only one of many types of secondary structure that DNA – a flexible polymer – can fold into. Much less is known about the other secondary structures, such as i-Motif (iM): how and when they form, what they do, how their structure relates to their role. Learning about them is fundamental to understanding biology, and targeting them could lead to new diagnostics and treatments for disease. iM specifically was discovered in 1993, initial assumptions that it could not exist at physiological pH were overturned in the 2010s, and its existence in organisms was proven in 2018. However, the methods used to do this relied on the cells being dead, preventing use in live organisms, or any study of cellular response combined with iM detection. Fielden & Waller’s project will build on their prior work on in vitro i-Motif detection with the aim of building metal-based small molecule probes that can enter live cells. These will detect iM by having a size/shape that tightly fits the iM structure, and interactions with iM which result in light emission from the probes being switched on. If successful, such probes could transform our ability to study iM in living systems and detect iM-linked diseases.