Research Projects

Juvenile hormones (JHs) are essential insect-specific hormones that regulate various physiological processes, including molting, metamorphosis, and reproductive maturation. Enzymes involved in the biosynthesis of JHs are being explored for designing and developing bio-rational insect growth regulatory molecules (IGRs). Farnesol dehydrogenase, a crucial enzyme in the JH synthesis pathway, is an attractive target for developing insect-specific potential anti-JH IGRs. The three-dimensional crystal structure of Helicoverpa armigera farnesol dehydrogenase enzyme (HaFDL) in complex with its cofactor NADP has been determined, representing the first recorded 3D-crystal structure of an insect farnesol dehydrogenase. The proposal aims to uncover the structure-function relationships of farnesol dehydrogenase to design insect-specific potential anti-JH IGRs that are highly action-specific and relatively safer in use compared to conventional insecticides. The HaFDL protein will be overexpressed and purified for structural, biochemical, and biophysical studies, and crystallization will be attempted to obtain native and substrate/product/inhibitor complexes. The crystal structure will be used for structure-based virtual screening of small molecule chemical libraries, pharmacophore modelling, and molecular docking studies to identify and rank potential inhibitory molecules. The promising molecules will be evaluated under in vivo conditions for their efficacy in inhibiting JH synthesis, reproductive potential, and their impact on the development of key cotton pests and other non-target insects. Successful completion of this study will significantly enhance our understanding of the structural determinants of HaFDL substrate specificity, paving the way for the future development of insect-specific and environment-safe IGRs for pest management.