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


   Department of Biosciences

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  Dr E Fitches, Dr J Gatehouse  Applications accepted all year round

About the Project

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 (CNS) of the target pest via the circulatory system. Recombinant 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 existing, well established fusion proteins contain a single toxin fused to the carrier but new research by the applicants suggest that efficacy can be further improved 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. This project benefits from a strong collaborative relationship with the industrial partner.
This project would appeal to students interested in the field of agricultural biotechnology and crop protection who have an interest in working with invertebrates. Experience in molecular biology, including the design and production of recombinant chimeric proteins, protein biochemistry and invertebrate physiology would be gained. In the laboratory we produce recombinant fusion proteins by bench-top fermentation of transformed yeast clones. Proteins are subsequently purified and a number of in vitro and in vivo techniques are used to characterize and evaluate the fusion proteins for crop protection. The project, conducted in collaboration with an industrial sponsor, would provide a solid foundation in applied research in the field of agricultural biotechnology.

Funding Notes

This project is in competition with others for funding. Success will depend on the quality of applications received, relative to those for competing projects. If you are interested in applying, in the first instance contact the supervisor, with a CV and covering letter, detailing your reasons for applying for the project

References

Nakasu, Y.E.T., Williamson, S.M., Edwards, M.G., Fitches, E.C., Gatehouse, J.A., Wright, G., Gatehouse, A.M.R. (2014) Novel biopesticide based on spider venom protein shows no adverse effects on honeybees. Proc. R. Soc. B, 281, 20140619.
Yang, S., Fitches, E, Gatehouse, J.A. (2014) Pyrethroid-resistant peach-potato aphid (Myzus persicae) also shows reduced sensitivity to an insecticidal fusion protein containing the sodium channel specific spider toxin Pl1a (amaurobitoxin). Pest Management Science 71, 951-956.
Yang, S., Pyati, P., Fitches, E., Gatehouse, J.A. (2014) A recombinant fusion protein containing a spider toxin specific for the insect voltage-gated sodium ion channel shows oral toxicity towards insects of different orders. Insect Biochem. & Mol. Biol. Vol. 47, 1-11.
Fitches, E.C., Pyati, P., King, G.F., Gatehouse, J.A.. (2012) Fusion to snowdrop lectin magnifies the oral activity of insecticidal omega-Hexatoxin-Hv1a peptide by enabling its delivery to the central nervous system. PloS one 7(6): e39389.