Functional genomics studies on nuclear receptors: Target sites for insecticide development and resistance management

Beetles are major pests and cause damage worth billions of dollars annually. Yet, very little is known on the physiology and development of beetles. Sequencing of Tribo/ium castaneum genome, availability of genetic strains and functioning of systemic RNA interference (RNAi) make T. castaneum the ideal model insect for beetle group. Nuclear receptors (NR) are classified by the presence of a DNA-binding domain and a ligandbinding domain and function as key control points in diverse signaling and metabolic pathways. NRs are naturally switched on and off by small molecule ligands with properties similar to insecticides. Therefore, NRs are attractive targets for developing new insecticides. Four insecticides targeting NR, ecdysone receptor, are being marketed world-wide. Seventeen more NRs are yet to be explored as insecticide target sites. A combination of post-genomic technologies, RNAi, quantitative real-time reversetranscriptase PCR, protein:protein interaction assays and microarray will be employed to study the function of 19 canonical NRs identified in T. castaneum. NR reporter assays will be developed and validated by screening a small library containing 50 probable NR ligands. T. castaneum strain that showed resistance against synthetic pyrethroids will be used to determine the role of NRs in insecticide resistance. At the completion of these studies, we will know the function of 19 canonical NRs identified in T. castaneum and we will have NR-based reporter assays to screen for new improved insecticides and supplements to existing insecticides for fighting resistance. USDA priority area addressed: Enhanced protection and safety of the nation's agriculture and food supply.