SBIR-STTR Award

We propose a Phase I program to evaluate the insecticidal properties and components of certain parasitic wasp venoms. Most insects, including most important crop pests. Are attacked by one or more species of parasitic wasps. The venoms of parasitic wasps are known to have a wide range of effects on their hosts, including paralysis, growth regulation, and suppression of the immune system. The base biological and physiological diversity of parasitic wasps suggests that their venoms are a potentially rich source of potent, selective, insecticidal toxins with novel, useful chemistries and modes of action. Such toxins may be expected to serve as leads for developing new classes of synthetic chemical insecticides and as the basis for recombinant biopesticides. Although available data are limited, they suggest that these venoms may provide the most potent insect-specific toxins identified to date. We have prepared a list of taxonomically diverse species, the venoms of which are likely to contain paralytic activities. In phase i, venom gland or whole wasp extracts will be surveyed for incapacitating activities against important lepidopteran crop pest. The biological and physical properties of the most effective activities will be further characterized. Based on these results, purification of the most effective toxins will be initiated.

We propose a Phase II program using toxins from parasitic wasps to develop methods for guiding the discovery of improved, highly selective chemical insecticides. The proposed program involves identifying at least two highly insecticidal, highly insect-selective toxins from parasitic wasp venoms, and using them as ligands for the development of high throughput receptor binding assays. Several suitable candidate venoms, with at least two distinct modes of action, were identified in Phase I and methods for purifying their active components are under development. In Phase II, these toxins will be radioactively labeled and used as radioligands to define the pharmacology of their target sites. All biological assays and receptor binding assays will be developed with a major agricultural pest, the tobacco budworm. Using highly selective toxins with great insecticidal potency in the ultimate target pest, and using the target pest for further assay development, is the definite aspect of the proposed program. Most efforts to employ receptor binding assays in insecticide discovery have involved the use of receptor preparations and ligands with questionable relevance. The research we propose, in contrast, will develop assay systems that are specifically relevant for a major crop pest.

Anticipated Results:
Successful completion of Phase II will provide new receptor binding assays for measuring chemical activity at target sites defined by toxins having great insecticidal potency and great selectivity for insects. These assays will be suitable for screening libraries of small organic molecules in Phase III, to identify molecules with significant activity at these target sites. Because they will use tissues from a major pest (the tobacco budworm), and toxins with high insecticidal activity in this pest, these assays will be of unique value in the discovery of effective chemical insecticides with improved environmental characteristics.