Inorganic - Nucleic Acid Interactions through Click Chemistry
The study of metallodrug-nucleic acid binding mechanisms and the associated conformational and structural changes that occur play an important role in drug discovery. In this group, we utilise a wide array of biochemical assays including fluorescence, absorbance, circular dichroism, on-chip microfluidics, and thermal stabilisation (amongst others) to uncover new metallodrug binding properties and nucleotide binding specificity. Interactions of novel metal complexes with DNA can provide valuable insights to the pharmacological profile of potentially new agents and insights towards their mechanism of action. A further area of intensive research in this group is the development of nucleic acid-metal complex hybrids for site-specific antisense application.
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.
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. To unravel these properties, an extensive range of cancer cell biology, molecular biological and microscopy experiments are applied to probe the mechanistic activity and redox targeting properties. Through the use of selective biomarkers, we can investigate cellular processes and pathways in comparison to carefully selected agonistic or antagonistic positive controls. This series of established molecular biological techniques particularly focuses on intracellular ROS production, organelle targeting, genotoxicity and the origin and activation of cell death pathways such as apoptosis and autophagy. Our group also holds extensive knowledge for in-depth analysis of results generated from the National Cancer Institute’s 60 cancer cell line screen, part of the Development Chemotherapeutic Program.