Serendipity can strike anywhere – including at academic conferences in Turkey.
In 2011, UQ molecular bioscientist David Craik was in Antalya for a meeting of the Society for Medicinal Plant and Natural Product Research to deliver a lecture on a family of peptides called cyclotides.
Found in the Butterfly Pea (Clitoria Ternatea) plant, his team was investigating cyclotides for their insecticidal properties.
Sitting in the audience was a fellow academic, Dave Leach, whom Professor Craik had last seen 35 years earlier when they did their PhDs in organic chemistry together at La Trobe University in Melbourne.
“We had a beer after the conference, and he told me he was working as a consultant to this company, Innovate Ag, and we realised we should make a connection,” Professor Craik recalls.
It was during this catch-up that Professor Craik learned that the research and development company based in Wee Waa, New South Wales, had started using the Butterfly Pea plant to develop a non-toxic, bee-safe insecticide.
Their work was sparked by a 2001 discovery by New South Wales Department of Primary Industries principal research scientist Dr Robert Mensah.
“He had noticed that Butterfly Pea tended not to get attacked by insects very much, and during trials for refuge crops in cotton, insects simply avoided it,” Professor Craik says.
“So they sort of knew this plant had some sort of insecticidal properties, but had no idea how it worked.”
Growth Agriculture, a major shareholder in Innovate Ag, was a commercial partner to the original project, and Innovate Ag was formed and purchased the technology for development in 2010.
Director Nick Watts says they created a working prototype that was an extract of Butterfly Pea, but wanted to know more about how the plant protected itself, and how the extraction could provide both direct toxicity and behaviour modification to insect pests.
"Identifying the active compounds in plants like ours is the proverbial needle in the haystack," he says.
Luckily, Professor Craik’s work is all about “unleashing the power of peptides” for real-world use in agriculture, medicine, and other fields.
He's even been recognised for it by The Australian's 2019 Research magazine – named Australia's top researcher in the field of medicinal chemistry.
Joining forces with Innovate Ag for an Australian Research Council (ARC) Linkage Grant, Professor Craik discovered that cyclotides were cross-linked by disulphide bonds, making them highly stable and ready for defensive action.
“An insect comes along, and these stable molecules interact with the insect’s gut to make them feel sick and not want to eat any more, which makes it go away,” he says.
“It’s similar to caffeine, which is a molecule that protects coffee beans from insects and pests, but we use it for other purposes.”
It's this property that makes the Butterfly Pea highly valuable as the main active component of a non-toxic, world-first plant extract bio-pesticide, designed to replace traditional synthetic pesticides, improve crop quality, and most importantly, be safe for bees.
The devastation of bee numbers around the globe has been well-documented as one of the most frightening potential fallouts from climate change.
Bee pollination is responsible for more than 30 per cent of global food production. If bees become extinct, whole food industries could collapse.
Mr Watts says products like Sero-X are a smart choice for those who want to eat more organically and do their bit to save the bees.
“The idea of using manufactured chemical substances to protect crops is a thing of the past,” he says.
Professor Craik says joining forces with UQ enabled Innovate Ag to confirm the science behind their game-changing product.
“It was crucial in their registration process to know what the active ingredients were. We now work with them to help get the extract registered in other countries around the world,” he explains.
“It’s been a really neat collaboration between practical people supplying the farming industry who didn’t know anything about cyclotides, and our people who didn’t know Innovate Ag were working on this product.”
Sero-X and its Clitoria ternatea extract are the first new active constituent and product to go from discovery and development right through the regulatory approval process in Australia.
The product is now registered for use in cotton and available under permits for a wide range of horticultural and tree crops.
Mr Watts says with full registration in brassica and a number of other horticultural crops just around the corner, it is vital to have the science to back up the product's efficacy.
“There are lots of plants out there with bio-activity against insects and lots of bio-pesticides that have been discovered, but very, very few of them get through the regulatory pathway because the understanding of those active ingredients just isn’t there,” he says.
While this is the first step in the peptide revolution, Mr Watts says it won't be the last.
"Pollinator populations and insect diversity as a whole are under threat around the globe, and cyclotides have the ability to reduce the reliance farmers have on synthetic compounds that can have devastating short and long-term effects.
“With this relationship, we can look at the next 10, 15, 20 years and know that we will always be able to be at the forefront of this revolution in agriculture.”
Professor Craik’s and Dr Leach’s chance encounter in Turkey was an important turning point in the development of Sero-X, and the discovery of cyclotides’ potential to revolutionise the agriculture industry was also largely a happy accident.
“We only began looking at the cyclotide molecule because of its unusual knotted structure,” Professor Craik explains.
“When we realised why it’s so stable, we thought we could use this to make medicines and agricultural products.”
He says this is a good example of how breakthroughs often come from curiosity – and he hopes this particular breakthrough will have much broader applications.
“I hope it’s just the start and there will be other products where we can try to reduce the burden of chemical insecticides, try to make agricultural products cheaper and safer.”
The medical potential comes from harnessing the molecule’s stability, evolved over millions of years, by altering certain sequences to act as blockers.
“A lot of our work on the medicinal side of things is to use this stable plant-derived peptide as a scaffold for making and designing medicines that people could then use for cancer, cardiovascular disease or pain,” Professor Craik says.
“We want cyclotides to save the world.”