Juvenile hormone (JH) is a major component of the insect endocrine system. JH is involved in regulation of an unusually extensive range of physiological and developmental processes. In addition to the control of insect molting and the establishment of reproductive maturity, it controls migratory and sexual behavior, reproductive diapause, caste determination, etc. The focus of this proposal is on the molecular genetic mechanism of JH action. In his previous work, the PI has described a group of genes, whose expression is induced by JH in Drosophila. One of the genes encodes the nuclear hormone receptor, E75A. Based on the observation that E75 is a primary JH target and its JH inducibility is conserved in evolutionarily divergent insects, the PI proposes a search for regulatory elements involved in the hormonal activation of E75 gene transcription. The bioinformatics approach will be followed up with functional assays in cultured cells. The second objective is to test the involvement of nuclear hormone receptor molecules in JH signaling. The Drosophila genome encodes 21 nuclear receptor superfamily members. To identify their involvement in JH signaling, the PI will employ RNAi, a functional gene silencing triggered by dsRNA. Suppression of nuclear receptors may confer a resistance to the JH activation of gene expression in cultured cells. The proposed research combines cellular and computational biology approaches to define molecular elements that are involved in genomic JH action and thus paves the way to an elusive JH receptor. Students will be involved in the scientific research through academic support programs that exist at Dartmouth College.