A plant-derived molecule with the ability to protect grain crops from a broad range of fungal diseases has been found to also kill human cancer cells.
The discovery was made by Australian agricultural biotechnology company Hexima Ltd, which is now developing the molecule for both crop protection and medical applications.
The company has built a special $2 million facility at La Trobe University’s AgriBiosciences precinct in Victoria to take the discovery further.
The molecule (a type of ‘defensin’ protein called NaD1) was discovered by Hexima’s chief scientist, Professor Marilyn Anderson, in ornamental tobacco plants where it protects the flower’s female stigma from an unusually broad range of fungal pathogens.
Those properties led to the peptide’s selection by Hexima for development within its crop-protection R&D program. GM corn expressing the tobacco defensin is already being tested at the university. The corn project is being undertaken with biotech company Du Pont Pioneer.
The cancer-fighting link came from parallel work by Dr Mark Hulett while researching how the tobacco defensin works at the molecular level and how this information might be useable in applications other than crop protection.
Dr Hulett, a cell biologist at the La Trobe Institute for Molecular Science, says the way plants protect themselves from different pathogens is a potentially significant – and under-explored – area of medical research. “The immune systems of plants have evolved sophisticated ways to attack and destroy the cellular viability of pathogens,” he says.
“It has created a whole array of biologically active molecules for us to explore for potential therapeutic applications in human medicine.”
With structural biologist Dr Marc Kvansakul (also of La Trobe University), Dr Hulett’s team used the Australian Synchrotron to solve the molecular structure of the defensin NaD1. This information helped explain how defensin disrupts the integrity of cell membranes in both fungal pathogens in crops and in human cancer cells.
“We found that the defensin works against a pathogen, such as a cancer cell, by binding to its outer membrane [via molecules called phosphoinositides] and in doing so disrupts the membrane’s connection to the cell’s internal skeleton. Like a parachute that has its cords cut, the membrane no longer holds its shape and bursts, killing the cell.”
Hexima is following up on the anti-cancer finding, with Dr Hulett’s research team now engaged in laboratory trials before progressing to clinical trials in humans.
“This has strong potential, although we are still looking at a timeframe of five to 10 years before we understand the full clinical potential,” he says. “The project really demonstrates the importance of preserving the genetic diversity of plants across different habitats. You just don’t know what might be locked away inside them.”
In the meantime, Hexima continues to exploit the finding for crop protection purposes. Hexima’s chief scientist, Professor Marilyn Anderson, has shown there are opportunities to transfer the defensin’s anti-fungal properties from tobacco flowers to agriculturally grown crops.
The primary strategy involves using the gene that encodes the defensin within a DNA construct that allows commercially grown crops to express the defensin molecule throughout the plant using GM technology. This strategy has the potential to extend the defensin’s anti-fungal properties from protecting ornamental flowers to entire crops.
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