Wilson da Silva, Sydney
THE fangs of Australia’s feared funnel web spider could contain an environmentally friendly pesticide. Active compounds in the venom have been found to attack only the nervous systems of insects, leaving large animals—and crops—unharmed.
The discovery was made by biochemist Glenn King and pharmacologist Merlin Howden, both at the University of Sydney. For the past two years the duo have been decoding the three-dimensional structure of the small protein fragments, or peptides, that are responsible for delivering the venom’s lethal neurotoxic effects.
One of the world’s deadliest spiders, funnel webs killed one person every four years on average before an effective antivenin became widely available in Australia in 1980. Funnel web venom is only lethal to the insects that are its natural prey, and humans. Larger animals and amphibians are naturally immune.
Using nuclear magnetic resonance spectroscopy and X-ray crystallography, King and Howden have mapped all 45 active compounds in the venom. Laboratory tests on the peptides revealed one specific to insect brain cells. Others were found to target human nerve cells. “It’s remarkable that parts of the venom affect humans and other parts are specific to insects,” says King.
The insect-killing compound holds open tiny pores in the membranes of insects’ nerve cells. Usually ions cycle back and forth through these pores to carry message pulses along the nerve. But the protein jams them open, sending amino acids, sugars, sodium, potassium and other substances essential to proper brain function gushing into the cell. Neurological activity is severely disrupted—with fatal consequences.
More recent work with student Xiuhong Wang has isolated the peptide fatal to humans. This works in a similar fashion to the insect-killing compound, but only affects human nerve cells.
Meanwhile, lab tests using brain cells from cockroaches and humans have confirmed that the insect-killing compound affects only insect pores and leaves human ones unaffected. King says that the venom has been shown to kill cotton bollworms, plague locusts, cockroaches and mealworms. “But it doesn’t kill any non-insect creatures it’s been tried on so far,” he says. “This could serve as a `natural’ pesticide.”
The researchers hope any resulting pesticide will be effective against the cotton moth, Helicoverpa armigera, which has developed resistance to many pesticides. It has even overcome cotton crops that have been genetically engineered to withstand it.
King is using the detailed map of the whole peptide to make a design template to produce synthetic analogues suitable for crop spraying. The researchers have applied to patent insecticides based on their findings. A paper on the work will be published in the June edition of Nature Structural Biology.
