Insecticide Design: Insights from Venomous Spiders

University Of Connecticut Health Center, Farmington CT

Investigators

Abstract

Arthropod pests destroy 20-30% of the world's food supply and are responsible for the transmission of many new and reemerging human diseases. These insect pests are usually controlled with broad-spectrum chemical insecticides. However, the long-term application of a small armament of insecticides that act on a handful of invertebrate nervous system targets has inevitably led to the development of resistance in most arthropod pests. This problem, along with concerns about the environmental and human health risks associated with certain agrochemicals, has stimulated the search for new insect control methods. This project focuses on the recently discovered families of novel invertebrate-specific neurotoxins in the venom of the lethal Australian funnel-web spider. These peptides are exciting insecticide leads because they are active against a broad range of arthropod pests and they do not act on conventional insecticide targets. In this project, detailed three-dimensional maps of the bioactive surfaces of these toxins will be constructed and their precise molecular targets will be identified using a combination of electrophysiological and genetic methods. Fundamental questions regarding expression and evolution of the toxins will also be addressed. This project will uncover new insecticide targets and enhance the utility of these toxins as leads for insecticide development. It is anticipated that this work will ultimately lead to a new generation of "environmentally-friendly" insecticides. The research will provide a fertile training ground for graduate students in the areas of biochemistry, structural biology, and insect control. The project will involve outreach activities such as public lectures, media interviews, demonstrations to high school students, and presentations at conferences and symposia.