Advanced discovery of RNA binding therapeutics using state-of-the art native mass spectrometry
RNA is emerging as an exciting new therapeutic target. Whilst non-coding RNA was once considered junk RNA, it has now been strongly implicated in many human diseases. Currently we lack approaches to find small molecules that bind to RNA and this limits the development of RNA targeting therapeutic. This project with develop native mass spectrometry, one of the most powerful structural biology methods, to characterise a variety of important RNA targets (aptamers, riboswitches, non-coding RNAs). nMS will then be utilised to complete small molecule screens against the RNA targets to identify novel RNA binding ligands that can be optimised through medicinal chemistry. This will lead to novel ligands that bind to RNA targets as a new mechanism for modulating disease and also provide new methods for other researchers to better study and understand RNA.
Primary supervisor: Professor Sally-Ann Poulsen
Other supervisor: Dr Frank Sainsbury
To apply: Contact Prof Sally-Ann Poulsen with your CV at s.poulsen@griffith.edu.au
Developing native mass spectrometry methods to characterise the interactions that drive biology
This project aims to develop native mass spectrometry methods for characterising challenging and unconventional targets that underpin emerging disease therapeutics. Native mass spectrometry is a rapidly growing biophysical technique – this project is one of few opportunities in Australia to develop skills with this emerging and continually developing methodology. Potential biomolecular targets to be investigated include soluble and membrane proteins and structured RNAs, and their complexes with other proteins, nucleic acids and/or lipid binding partners. Development of these methods will facilitate the fundamental understanding of these molecules and further drug discovery by allowing fragment, or other, screening campaigns to discover novel binding compounds, or characterise previously identified therapeutic binding compounds. This can be applied to various diseases areas including cancer and infectious diseases.
Primary supervisor: Professor Sally-Ann Poulsen
To apply: Contact Professor Sally-Ann Poulsen with your CV at s.poulsen@griffith.edu.au
Identifying ligands with almost unlimited potential for therapeutic development
The traditional highly selective small molecule that acts on a single disease-associated target is now only one component of a "therapeutic modality smorgasbord", contributing breakthrough advances to address unmet health needs and benefit patients. New therapeutic modalities offer vastly wider target coverage and are contributing many recent first-in-class therapies, for diseases of unmet need. One such modality is targeted protein degradation (TPD). TPD provides an almost limitless opportunity to degrade any protein and is arguably providing one of the most compelling approaches to modern drug discovery. The development of TPD as a therapeutic modality has however necessitated that the common biophysical tools used in structural biology are optimized to characterise the complexity of biomolecular interactions in play with this modality. The focus of this project is to explore the nexus of native mass spectrometry (nMS) with TPD to characterise the biomolecular interactions central to the mechanism of action of TPD.
Primary supervisor: Professor Sally-Ann Poulsen
Other supervisor: Professor Kathy Andrews
To apply: Contact Professor Sally-Ann Poulsen with your CV at s.poulsen@griffith.edu.au