13 December 2023

Professor Richard Lewis and his team from the Institute of Molecular Bioscience at University of Queensland made a notable discovery early in their research after a lab assistant observed one could milk cone snails for venom much more quickly if you gave them “a poke or two”.

Cone snails are a highly venomous sea snail which produce venom peptides that act very selectively across a range of neurological targets associated with pain pathways, presenting a unique opportunity to develop new pain therapies.

The lab assistant, Dr Sebastien Dutertre, compared the samples of the venoms collected and discovered cone snails produce one type of venom when in attack mode (after a poke), and another when hunting for their prey (either fish, worms or other molluscs, depending on the species).

“The discovery of these attack and defence peptides [peptides are miniproteins] in different venom allowed us to think more broadly about the evolutionary drivers of selection for these,” Professor Lewis says.

The team focused their hunt for pain target modulators in the defensive venoms, isolated these to purity, and studied how selective and potent they were.

Professor Richard Lewis

Photo: Professor Richard Lewis

“We found we could get good inhibition at certain calcium and sodium channels important in pain pathways, but they were highly selective and didn’t work on related channels that might cause side effects.”

NHMRC Program Grant funding provided support for teams of researchers to pursue broadly-based, high-quality, collaborative research addressing complex problems.

Professor Lewis’ team brought in another collaborator, Professor Glenn King, into its third round of funding to broaden its scope from cone snails to include Australian spiders. Professor King is co-founder of Ifensa Bioscience, a start-up trialling a drug candidate discovered in funnel web spider venom and designed to prevent tissue damage caused by heart attack and stroke.

“Similarly to cone snails, spiders love to make venom peptides,” Professor Lewis says.

The team also collaborated with Professor David Julius of the University of California, a recipient of a Nobel Prize for his work on molecular mechanisms of pain sensation and heat, and Adelaide-based Professor Stuart Brierley, whose expertise on the causes of and treatments for Irritable Bowel Syndrome (IBS), supported their discovery of a new way to treat IBS-related gut pain.

Successive grants over 15 years allowed the team to work together with complementary subject matter experts when they needed to.

“This allowed the team to efficiently cover a broad range of research areas and pursue discoveries in fantastic depth,”

“The three grants gave us the best research opportunities we could imagine.”

Professor Lewis’ previous research into cone snail venom and pain relief was also part of NHMRC’s Ten of the Best — Research Projects 2011.

Next steps

This NHMRC-funded research program led to the identification of new analgesic drug targets and pathways associated with specific types of pain and developed compounds that can potentially and selectively inhibit these targets. These discoveries promise to alleviate chronic and severe pain without the addiction, tolerance issues or side effects that currently limit the usefulness of pain drugs.

While cone snails had always been collected and brought to the lab from the Great Barrier Reef, the team found that some of the cone snails in the tanks were laying eggs. It was discovered that the juvenile cone snails could be grown in tanks, and be milked and studied on site, revealing that juvenile cone snails target different prey (worms vs fish) and produce venom peptides that are distinctly different to those of adults.

Breakthroughs like these enhance University of Queensland’s reputation as the leading institute for venom-based drug discovery in the world and help inspire the next generation of researchers.

Team Members:

  • Professor Richard Lewis, University of Queensland
  • Emeritus Professor Paul Alewood, University of Queensland
  • Professor David Adams, University of Wollongong
  • Professor Macdonald Christie, University of Sydney
  • Professor Glenn King, University of Queensland
  • Professor Irina Vetter, University of Queensland
  • Professor Rob Capon, University of Queensland
  • 2021 Nobel Laureate Professor David Julius, University of California, San Francisco
  • Professor Stuart Brierley, Flinders University, SAHMRI
  • Professor Patrick Sexton, Monash University
  • Professor Arthur Christopoulos, Monash University

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