Pharmacology of marine toxins

Venoms: predatory, defensive, and a treatment for chronic pain.

Venoms have evolved to be both predatory and defensive. Venoms can immobilize prey and typically either cause or block pain.

The peptides within venom are targeted, specific, and often surprisingly effective on humans. These features make them important research tools and potential therapeutics.

The Lewis Group use mass spectrometry, transcriptomics and molecular pharmacology approaches to discover and characterize venom peptides, with the ultimate objective of discovering new drugs for chronic pain.

“We work on the scientific frontier, motivated by making discoveries that have the potential to change people's lives,” said Group Leader Professor Richard Lewis.

Research overview

The Group has particular expertise in marine toxins, in particular, conotoxins from the predatory cone snail, as well as spider venom.

The cutting edge facilities at IMB, such as the Mass Spectrometry Facility, increase the ability of researchers to investigate the genomes of animals and uncover gems.

“Once we have discovered a useful peptide, we put it on a range of different assays to identify its strengths and weaknesses.

“We then modify the peptide to make it better, overcoming issues like chemical instability,” said Professor Lewis.

Peptides found in nature rarely have all the features required to make an effective analgesic. The Lewis Group is expert in making new and improved molecules.

The ultimate objective is to translate these discoveries commercially so they can become the pain drugs of the future.  

“Our research also explores the mechanisms of how the body feels pain by studying the effects of peptides on pain pathways within the body.”

Several conotoxins discovered by The Lewis Group have been taken into the clinic, including Xen2174 for severe pain.

Chronic pain is one of the most under-recognised and undertreated medical problems, with one in five Australians, and one in three Australians over the age of 65, suffering from chronic pain.

Research projects

Currently we are investigating conotoxins that selectively target the nicotinic acetylcholine and NMDA receptors, the voltage sensitive calcium and sodium channels, and the noradrenaline transporter. Complimentary interactions between conotoxins and their receptor are being established to better understand where and how they act at the molecular level. The aim of this research is to develop research tools and potential therapeutics for poorly treated diseases such as chronic pain. This research involves assay-guided isolation of venom peptides, peptide synthesis, tissue pharmacology, radioligand binding and electrophysiological studies, as well as receptor mutagenesis, modelling and docking.

Research training opportunities

Research title: Venoms to drugs

Summary of research interests: My group focuses on the discovery and biochemical characterisation of venoms and marine toxins, especially the conotoxins produced by cone snails to rapidly immobilise their prey. These toxins modulate a variety of membrane proteins, including important drug targets like sodium and calcium channels, nicotinic acetylcholine receptors (nAChRs), monoamine transporters, and G-protein coupled receptors. Their high selectivity makes them important research tools and potential therapeutics. Through a multidisciplinary research program, including peptide and target molecular pharmacology, and integrated proteomics and transcriptomics, we continue to discover and develop the potential of these interesting molecules, particularly in the area of pain research.

Traineeships, honours and PhD projects include

  • Discovery of novel analgesic venom peptides from cone snails
  • Integrated proteomics and transcriptomics to investigate the evolution and structure-function of cone snail venoms
  • Ultrastructural studies of the venom apparatus of cone snails
  • Mechanisms of venom peptide regulation in cone snails
  • Genomics studies of cone snails.

Contact: Professor Richard Lewis

+61 7 3346 2984
r.lewis@imb.uq.edu.au


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Engagement and impact

 Professor Lewis' research on novel analgaesics from Australian venomous animals has the potential to change the way severe pain is currently treated. His research on ciguatera has the potential to improve the management of this severe illness associated with the consumption of tropical reef fish that affects ~50,000 people per annum.

Several conotoxins discovered by our scientists have been taken into the clinic, including Xen2174 for severe pain. In addition, we are studying how another class of marine toxins called ciguatoxins produce the debilitating disease known as ciguatera.

During the past 12 months, we have discovered new mechanism of peptide diversification through processing and transcriptomic messiness; identified peripherally analgesic ω-conotoxins, which are being developed as a new pain treatment; and defined a key role of potassium channels in the activity of nerves associated with cold pain.

In addition, we have worked closely with industry partners to develop our novel findings, supported with the award of two new ARC Linkage grants to investigate spider toxins and small molecule blockers of sodium channels in pain pathways.

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Coming soon.
 

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Prof Richard Lewis

Professor Richard Lewis

Group Leader, Chemistry and Structural Biology Division

Director, Centre for Pain Research

  +61 7 3346 2984  
  r.lewis@imb.uq.edu.au
  IMB Researcher Profile
  Centre for Pain Research


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  Group Leader

  • Professor Richard Lewis

    Director, IMB Centre for Pain Research
    Professorial Research Fellow - GL
    Institute for Molecular Bioscience

  Researchers

  Students

  • Mr Md. Mahadhi Hasan

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Miss Dan Wang

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Mr Kapil Jain

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience

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