This award will support collaborative research between Prof. George P. Georghiou of the University of California, Riverside, and Dr. Nicole Pasteur and colleagues at the Institute of Evolutionary Sciences of the University of Montpellier II, France, in the area of insecticide effectiveness. The objective of this research is to identify the genes responsible for resistance to insecticide in insects, and then to use this knowledge to devise specific and practical diagnostic tests for the detection of resistance mechanisms in individual insects. A combination of toxicological, genetic, biochemical/physiological, and molecular (DNA) methods will be used. Primary emphasis will be on the genetic characterization of the changes at the molecular level, which underly various specific resistance mechanisms. Efforts will be made to determine changes in the structure of genes, as well as to isolate and purify the proteins that are involved in other resistance mechanisms. The French and U.S. investigators have a long history of productive collaboration. Joint development of biochemical tests for the detection of resistance mechanisms will be carried out on laboratory and field colonies of mosquitoes and house flies. The two laboratories have complementary resources in the areas of toxicology, physiology, biochemistry, and molecular genetics. This research could have important applications in the fields of insect control and crop management.