Research areas
Drug-DNA Interactions
The study of drug-DNA binding modes and the associated conformational and structural changes play an important role in drug discovery. We apply a number of biophysical and molecular assays including fluorescence, absorbance, circular dichroism, on-chip microfluidics, microscale thermophoresis, and thermal melting to discover potential new binding properties and nucleotide binding specificity. To read more about our work in this area see:
Hybrid therapeutic nucleic acids
We are focused on the development of nucleic acid-metal complex hybrids for antigene and artificial gene editing applications. We have developed methods to attach artificial metallo-nucleases and platinum(II) crosslinking drugs to triplex-forming oligonucleotides (TFOs) using nucleic acid click chemistry. We have established new methods to introduce stable azides into DNA binding scaffolds that can be incorporated into oligonucleotides by solid-phase synthesis or single nucleotide incorporation-primer extension (SNI-PEX). A number of assays have also been established in the group to probe the target binding properties of these hybrids using UV- and fluorescence-melting, microscale thermophoresis, multiplex PAGE, and real-time polymerase chain reactions. To read more about our work in this area see:
DNA Damage and Repair
The catalytic production of reactive oxygen species (ROS) by copper and iron complexes is now recognised as a major mechanistic model in the design of new materials that can manipulate nucleic acid structure. Accordingly, our group are focused on the development of new copper-based materials that mediate ROS DNA damage. These materials have uses in both medicinal chemistry and genome engineering. Methods for probing oxidative DNA damage available in our group include electrophoresis, flow cytometry, confocal microscopy, atomic force microscopy, fluorescence spectroscopy and qPCR. Research in this area has been highlighted in Chemistry - A European Journal (2019), Nucleic Acids Research (2018) and Molecules (2019).
Chemotherapeutic Drug Development
Elucidating the mechanism of cytotoxic action for metallodrug leads is a key element of our group and aids us in the discovery of new and effective chemotherapeutic agents. Through the use of selective biomarkers, we can investigate cellular processes and pathways, intracellular ROS production, organelle targeting, genotoxicity and the origin and activation of cell death pathways. Our group also holds extensive knowledge for in-depth analysis of results generated from the National Cancer Institute’s 60 cancer cell line screen. Our work in this area has been highlighted in Redox Biology (2017), Molecular Pharmaceutics (2018) and a Royal Society of Chemistry book chapter in Metal-based Anticancer Agents (2019).