Developing peptide-based pain therapeutics

Chronic pain affects over 3 million people, including 1 in 5 Australians aged 45 and older. Traditional analgesics, such as opioids, cause severe side effects and are highly addictive, hence we aim to develop non-opioid treatment alternatives.

Conotoxins, peptides found in the venom of marine cone snails, are of particular interest due to their small size and diversity. These peptides target a wide range of human voltage-gated ion channels, nicotinic acetylcholine receptors, and G protein-coupled receptors involved in pain pathways, making them promising drug leads and valuable research tools. However, these molecules are often unsuitable for direct use in their native forms due to a lack of selectivity and unfavourable pharmacokinetics. This project focuses on determining the structure of selected conotoxin-bound receptors to rationally design potent and selective analogues, as well as developing chemical strategies to enhance the drug-like properties of these peptides for long-lasting analgesic effects.

This project combines multiple disciplines, including peptide chemistry, medicinal chemistry, electrophysiology, and structural biology. The successful candidate will design and chemically synthesize peptides using an automated peptide synthesizer, and characterize them using various analytical techniques (HPLC, LCMS, NMR, etc.). Additionally, the candidate will perform functional and stability assays and collaborate with an international expert on structural studies using cryo-EM microscopy.

The project will be conducted in the group of Prof. David Craik, Director of the ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) at UQ. Prof. Craik is a pioneer in the discovery of ultra-stable cyclotides and has extensively studied conotoxins to elucidate structure-activity relationships. Our lab has a diverse range of expertise, including chemists, biochemists, molecular biologists, and bioinformaticians, all of whom play a vital role in the student’s professional development.

The PhD project will leverage key resources from the lab: peptide synthesis (three automated peptide synthesisers, nine HPLCs), NMR spectrometers and access to cutting-edge mass spectrometer facilities. The Institute for Molecular Bioscience (IMB) at UQ is renowned for its state-of-the-art facilities and vibrant research environment. Additionally, the student will benefit from the activities of CIPPS, such as scientific writing workshops, career development programs, and annual symposiums.