Tailoring specific lethal control agents

  • Possum eating a birds egg. Image - Nga Manu Images

    Possum eating a birds egg. Image - Nga Manu Images

Leader: Brian Hopkins, Manaaki Whenua

Mission Statement

Using genome mining to develop species-selective toxins that could be used at landscape-scale to maintain NZ’s economic and environmental status whist being acceptable to communities and individuals, and to position New Zealand at the forefront of thought leadership in sustainable, species-selective pest control.

Summary

Controlling possums is a national priority if we are to reverse the decline in native species and keep livestock TB-free. Landscape-scale control requires poisons, as trapping is too costly. However, current poisons, e.g. 1080 and anticoagulants, are controversial due to risks to non-target species, environmental persistence and the potential for entry into the food chain.

We will use a new application of genome mining (a technology developed by the pharmaceutical industry to discover targets for drug development) to identify possum-specific genes suitable for the development of species-selective toxins – their ‘Achilles Heel’. The possum-selective poisons will have little or no effect on non-target species. These toxins can be used in conjunction with current poisons, greatly reducing the amounts needed, and possibly replacing them altogether. As a consequence, the environmental impact of large-scale pest control operations will be markedly reduced

Once perfected the technology can be adapted to a wide range of economic and environmental pests, e.g. stoats, rats and mice and will position NZ at the forefront of thought leadership in sustainable, species-selective pest control.

Species-selective pest control will help Predator Free NZ and TBfree NZ achieve their goals and enhance Primary Industry’s sustainability credentials. These toxins will support tourism by safeguarding NZ’s natural environment and biodiversity. In particular, taonga species of importance to Māori will be protected.

By transforming biodiversity gains, the provision of safer pest control tools will support NZ’s tourism and recreation sectors worth ~$9.4B p.a. New tools will also protect the large-scale possum management that is currenly carried out using 1080 (the primary control tool). If 1080 is restricted or banned leading to an uncontrolled TB outbreak New Zealand could face trade losses of up to $14B p.a.

This project is aligned to MBIE funded project C09X1615 Using genome mining to identify targets for developing species-selective toxins.

This research aims to develop possum-selective toxins that will be more acceptable to the public as they will have little/no effect on non-target species. We hypothesise ;this can be achieved by using genome mining to identify possum-specific targets, their “Achilles Heel”, suitable for lethal intervention.

We hypothesise that genome mining technologies can identify possum gene targets suitable for selective toxin development. We base this theory on the practice of the pharmaceutical industry, which employs genome mining to discover targets for therapeutic intervention, and the fact that genome mining has been used in invertebrates to develop more specific and safer control tools.

Genome mining is a relatively new technique that involves analysis of the entire genome of a species. As the possum genome has not been sequenced, we will initially use related marsupial genomes as surrogates. We will use two separate approaches.

  • The first approach will target G-protein coupled receptors (GPCRs) sufficiently differentiated in the possum to achieve species specificity. We will use world-leading high throughput screening (HTS) robotics located at the Scripps Institute, Florida, to screen their large compound libraries (currently >650,000) to identify possum-selective active compounds. The discovery of totally novel compounds active at the possum receptors will not only drive possum-selective toxin development, but also generate new knowledge and understanding of possum genetics, pharmacology and toxicology.
  • The second approach targets genes that are well described in the literature as leading to acute death when their activity is disrupted. Specificity will be achieved by developing highly possum-specific small interfering RNA (siRNA) gene silencing molecules as toxins, which will inactivate the target genes and cause species-specific death. If either approach is successful, we will have identified the world’s first possum-selective toxin.
  • Specific lethal control agents (and advanced delivery systems) for priority small mammal /invertebrate pests and pathogens
  • Safer toxins that can be used in sensitive locations such as processing plants, warehouses and schools
  • Technology thatcan be adapted to a wide range of economic and environmental pests, e.g. stoats, rats and mice
  • Improved possum-control programmes that can cover large contiguous areas
  • Once perfected the technology can be adapted to a wide range of economic and environmental pests, e.g. stoats, rats and mice.

Members of the team are Dr Brian Hopkins (Manaaki Whenua), Dr. Katherine Horak (USDA-APHIS, Colorado, USA), Prof Patricia McDonald (Scripps Institute , Florida, USA), and Dist. Prof. Margaret Brimble, (University of Auckland, NZ).

The team is experienced in development and commercialisation of toxins (e.g. optimising formulation, field trials, and registration processes).