Protein engineering to enhance the commercial potential of novel fusion protein based biopesticides.

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Crop protection has become increasingly problematic due to the withdrawal of chemical pesticides from the marketplace and a shortage of new actives concomitant with the widespread development of resistance to the few products currently permitted for use. The applicants have patented an approach that transforms naturally derived peptides that lack oral toxicity, such as paralytic toxins produced by spiders to capture prey, into orally effective biopesticides. Invertebrate specific toxins are fused to a "carrier" protein able to cross the gut wall and ingestion of the fusion protein enables transport of the toxin to the central nervous system of the target pest via the circulatory system. Recombinant prototype fusion proteins produced in yeast are effective against a range of crop pests, including slugs, beetles and aphids, but have no deleterious effects on bees. Commercial exploitation of this technology through exogenous applications (e.g. baits and sprays) for the control of crop pests is being developed in collaboration with the industrial partner. The pool of available invertebrate specific peptide toxins that target different voltage gated ion channels for use in the generation of fusion proteins is increasing as research to characterize spider venom toxins advances. The existing, well established prototype fusion proteins contain a single toxin fused to the carrier but new patentable research by the applicants has demonstrated that efficacy can be further enhanced through protein engineering. The project seeks to explore opportunities to build upon recent results to enhance efficacy and thereby commercialisation prospects for this novel technology. The host laboratory has extensive experience in the design and production of recombinant fusion proteins that will form the basis of the research programme to be conducted by the student. Expertise in invertebrate physiology will further support research to evaluate the efficacy and mode of action of novel fusion proteins against crop pests. This project benefits from an established collaborative relationship with the industrial partner. The input of the CASE partner is essential for ongoing collaborative R & D to develop biopesticidal fusion proteins as a platform technology. Input from the non-academic partner will ensure that the proposed research project focus and outputs have the best chance of being successfully translated for adoption in a commercial setting.