This project represents basic research into how small hormonal and neurotransmitter molecules called peptides are used as messengers between cells and organs. We are attempting to discover how information is written on the structure of these small molecules and read by the target tissues. What are the rules of this molecular language? This type of basic information has potential for future application indirectly to the development of new pharmaceuticals for various human and animal diseases, and directly to the applications in agriculture and the control of vector-borne disease. Utilizing mosquitos as subjects, we limit the use of vertebrate animals and can economically obtain millions of insect subjects for our experiments. Also, by using mosquito subjects, we can direct the results of the research toward the development of a new generation of potential-specific insecticides that have potential for removing harmful effects to humans, beneficial insects and the environment. Specifically, the project is designed to isolate and determine the structure of peptides that effect a physiological process critical to mosquito survival, water and salt elimination. The structures of these naturally occurring peptides will allow synthetic versions of the native peptides to be prepared for the generation of antibodies and for receptor investigations. The antibodies will be used to locate sites of storage and release of the peptides within the mosquito. This should help determine if each peptide is a neurohormone, a neurotransmitter or a extraneuronal peptide. Synthetic analogs of the native peptides will be designed to probe the receptor(s) tissue location, molecular structure, and binding site surface. The interaction between receptors and peptides are a critical and perhaps the most important single form of intercellular communication that integrates a collection of cells into an organism.
