The Department of Biological Sciences at the University of Notre Dame is pleased to present a seminar by Walter Leal, Ph.D., Professor of Biochemistry in the Department of Cellular and Molecular Biology at the University of California-Davis.
Prof. Leal's research statement:
My current research is aimed at unraveling the molecular mechanisms that make the insect’s olfactory system so sensitive and selective. Insect prominence among other animals is due in large part to a key physiological element for their survival and reproduction - a refined olfactory system. Olfaction is orchestrated at various levels starting with reception of odorants at the periphery, processing and integration of olfactory and other sensory modalities in the brain, and ultimately translation of olfactory signal into behavior. Thus, the cornerstone of a sophisticated olfactory system is the ability of the insect’s peripheral system to selectively detect and rapidly inactivate minute amounts of odorants. Reception of odorants is mainly mediated by three olfactory proteins, namely, odorant-binding proteins (OBPs), odorant receptors (ORs), and odorant-degrading enzymes (ODEs). OBPs are involved in the uptake, transport and delivery of odorants to ORs.
By using biochemical, electrophysiological, RNAi, and kinetic studies we have demonstrated that OBPs are essential for the sensitivity of moth’s olfactory system. In collaborations with structural biologists, including UC Davis colleagues, we study the molecular mechanisms of odorant binding, release, and transport, including novel, pH-dependent conformational changes in moths and mosquitoes. By comparative kinetic studies of odorant degradation by recombinant and native enzymes we have demonstrated for the first time that ODEs are involved in the fast inactivation of odorants. Using bioinformatics approaches and focusing on sequences and predicted topologies of multiple ORs activated by common odorants, we investigate potential binding sites. We use the Xenopus oocyte recording system no only to probe the issue of receptor selectivity, but also to de-orphanize receptors. We prepare point-mutated ORs and compare their response with those of wt receptors. Additionally, we probe wt and mutated receptors with odorant analogues.
Albeit fundamental in nature, this research has short, medium, and long-term societal benefits. Insects are extremely successful animals whose lives intertwine with ours. They may be vegetarian and harmful to our food supply as well as vectors of pathogens that inflict tremendous suffering and human loses. Thus, a better understanding of the molecular basis of insect olfaction may facilitate the design of eco-friendly chemicals to controls insects of medical and agricultural importance. Additionally, our understanding of the molecular making of a selective and sensitive olfactory system may pave the way for the design of insect-inspired sensors and other electronic devices.