Identify The Beetle Ion Transport Peptide Receptor And Synthesize Antagonists

Mealworm larvae

Most commercially used insecticides poison insects by acting on the nervous system, which has more similarities to, rather than differences from, our own. Therefore all commercial insecticides which kill insects quickly have varying degrees of toxicity to non-target organisms, presenting calculated risks in their use.

Two types of insecticides have been developed which mimic the insect juvenile hormone and the molting hormone; they are known commercially as methoprene and MIMIC. These insecticides act on processes unique to insects and to crustaceans, and both are exceptionally safe to higher animals. However, they have a very slow mode of action, which limits their utility for control of most pest insects, because a treated insect will continue to consume the crop they are eating before expiring.

This project investigates a receptor for the beetle antidiuretic mini-protein University of Nevada, Reno scientists previously identified. The messenger RNA (encodes a chemical “blueprint” for a protein product) are very large and hard to clone, so we used Malpighian tubules (type of excretory system) from Tobacco Hornworm rather than Mealworm as originally planned. The team has now fully cloned two receptors from tubules, and partially cloned two that are more abundant in the hindgut, midgut, and trachea.

Research has shown that knocking out the gene for ion transport peptide has lethal effects in Mealworm Beetles; this is only the second peptide hormone where knock out experiments have shown the absence of the peptide to be fatal.

Our objective is to isolate the receptor for ion transport peptide (ITP) from Mealworms and to test its activity with Flour Beetles ITP; this species is extremely closely related to Mealworms. We are also synthesizing analogues of Flour Beetle ITP which bind to the receptor, but do not activate it and block the ability of normal ITP to bind to the receptor; these are termed receptor antagonist. Then we will test the biological activity of these antagonists in live insects.

It seems likely that they will be harmful to the insect, perhaps killing it. If these peptides do have harmful effects on insect survival, this means that chemicals with this type of activity should be good insecticides. Ultimately it will be necessary to develop small molecules with the same activity, because large peptides like ITP are not able to penetrate insect cuticle and therefore are not inherently good candidates for insecticides.