Metallo-Supramolecular assemblies that recognize key nucleic acid targets and their action in cells

Skills and Training. This project is an exciting interdisciplinary research project drawing on the skills and knowledge of supervisors across the University and with skills in synthetic chemistry and supramolecular design, cellular toxicology and actions against cancers, viruses and bacteria, imaging techniques and computational data and image analysis. You will develop skills in synthesizing and characterizing supramolecular assemblies and fluorescent supramolecular compounds, handling and treating cells, fluorescence imaging microscopies, electron microscopies and computational approaches to image and data analysis. To support you in gaining these skills, you will undertake a range of interdisciplinary taught and practical skills modules at the outset of the PhD.

Background: The aged population endures enhanced susceptibility to viral infections and subsequent superimposed bacterial infections. Such infections not only induce higher morbidity and mortality in older people, but also appear to be increasing in number. Increasing anti-microbial resistance exacerbates this problem. New types of anti-viral and anti-biotic agents that act through new biological targets and mechanisms are needed to meet this challenge.
RNA and DNA are particularly attractive targets to fight both viruses and bacteria: their RNAs, especially, and their DNAs, have features such as bulges, junctions and folds that can be specifically recognised and used to block activity. We have developed a new class of nanosized, ‘supramolecular’ agents that recognise, in a novel shape-specific way, some RNA- and non- canonical DNA-structures notably Y-shaped junctions and bulge structures. Preliminary work has demonstrated that this gives rise to novel anti-viral and anti-biotic actions.

Aims (i) To explore the biological activity of our bulge-recognising drugs in different environments, to establish their scope and potential as anti-bacterials and anti-virals. (ii) To gain a detailed understanding of the biological mechanisms, localisations and actions inside cells. (iii) To use this to design new metallo-supramolecular drug agents optimised for anti-viral and anti-microbial action with low mammalian toxicity, acting against different target structures.

Scientific outcomes The project will develop a new class of RNA/DNA-binding agents targeted at specific structures and their use as anti-viral and anti-microbials. We envisage publications arising from the compound design and preparation (nano-chemistry journals), the uptake and localisation and in cellulo biomolecular interactions (interdisciplinary chemistry-biomedicine journals), and in their anti-viral and anti-microbial efficacies (biological/biomedical journals). Computational aspects will be inherent to the studies and incorporated within the interdisciplinary papers.