Chemoreception: Linking Sequence, Structure, Mechanism, and Inhibition

With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, Professor Smita Mohanty of Oklahoma State University is studying the biochemical mechanisms of molecular signaling in a lepidopteran insect to understand how an odor is detected and communicated from the female to the male within a species during the mating process. Responding to chemical stimuli such as odors is a fundamental behavior of all organisms. This project will utilize biophysical and biochemical experiments to discover the basic mechanism of odor communication in an invasive agricultural pest. Structure-based computationally designed molecules will be synthesized in collaboration with Professor Frank Foss of University of Texas at Arlington and tested in the Mohanty laboratory for their ability to competitively bind to the odor-binding protein molecules to inhibit the sensing of female-secreted scent by the male to disrupt the mating process. Knowledge gained from this research could potentially bridge the fundamental gap in the understanding of the mechanism of sense of smell in voracious agricultural pests, as well as pave the way for the development of novel, species-specific, and environmentally friendly odor mimetics as alternatives to harmful pesticides, for bio-rational insect control. Students at the undergraduate and graduate levels will be trained in state-of-the-art synthesis and instrumentation including a newly acquired 800 MHz NMR statewide resource, thus preparing the future generation of teachers, researchers, and innovators. Insects use insoluble fatty acid (FA) derivatives as highly specific signaling molecules. Pheromone binding proteins (PBP) ferry the fatty acid odor to the odorant receptor across the aqueous sensillar lymph that surrounds the dendrites of odor-sensitive olfactory neurons. This project will employ an integrated approach involving techniques used in molecular biology, biochemistry, biophysics, computational chemistry, and synthetic organic chemistry to identify the chemical signatures in the PBP sequence that dictates the mechanism of odor binding and release in an invasive agricultural pest. Biophysical data collected on Ostrinia furnacalis PBP2 (OfurPBP2) suggests that this protein binds lipids and releases them through a distinct mechanism involving a molten globule state. Mutation of functionally important residues will be carried out to unravel the mechanistic details to gain insight into the novel mechanism of lipid binding and release. Using computational methods, a structure-based design of pheromone mimetics will be performed. These mimetics will be synthesized to develop a competitive inhibitor that will be tested using a competitive binding assay. Results of this study could help unravel the distinct mechanisms of chemical sensing in Ostrinia species and will provide a foundation for the rational design of eco-friendly biomimetic inhibitors for insect control. Educational and outreach activities will leverage ongoing efforts at both institutions to recruit and train undergraduate students from across the country. This project is jointly funded by the CLP, and the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.