Leal, Walter - University of California, Davis - College of Biological Sciences

研究领域

Research in my lab 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 and molecular approaches coupled with the Xenopus oocyte recording system we investigate how ORs contribute to the selectivity of the insect’s olfactory system.

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Xu, P., Choo, Y. M., De La Rosa, Alyssa, and Leal, W. S. Mosquito odorant receptor for DEET and methyl jasmonate Proc. Natl. Acad. Sci. USA, October 27, 2014, doi: 10.1073/pnas.1417244111 Leal, W. S., Choo, Y. M., Xu, P., da Silva, C. B., and Ueira-Vieira, C. Differential expression of olfactory genes in the southern house mosquito and insights into unique odorant receptor gene isoforms Proc. Natl. Acad. Sci. USA, October 28, 2013, doi: 10.1073/pnas.1316059110 Leal, W. S. Healing power of honey. Proc. Natl. Acad. Sci. USA May 28, 2013 vol. 110 no. 22 8763-8764 Damberger,F. D., Michel, E., Ishida, Y., Leal, W. S., and Wüthrich, K. 2013 Pheromone discrimination by a pH-tuned polymorphism of the Bombyx mori pheromone-binding protein Proc. Natl. Acad. Sci. USA, October 24, 2013, doi: 10.1073/pnas.1317706110 Zhu F, Xu P, Barbosa RM, Choo YM, Leal WS. RNAi-based demonstration of direct link between specific odorant receptors and mosquito oviposition behavior. Insect Biochem Mol Biol. 2013 Oct;43(10):916-23. doi: 10.1016/j.ibmb.2013.07.008. Epub 2013 Aug 2. PubMed PMID: 23911547. Xu P, Leal WS. Probing insect odorant receptors with their cognate ligands: insights into structural features. Biochem Biophys Res Commun. 2013 Jun 7;435(3):477-82. doi: 10.1016/j.bbrc.2013.05.015. Epub 2013 May 11. PubMed PMID: 23673297 Xu P, Choo YM, Pelletier J, Sujimoto FR, Hughes DT, Zhu F, Atungulu E, Cornel AJ, Luetje CW, Leal WS. Silent, generic and plant kairomone sensitive odorant receptors from the Southern house mosquito. J Insect Physiol. 2013 Sep;59(9):961-6. doi: 10.1016/j.jinsphys.2013.07.004. Epub 2013 Jul 19. PubMed PMID: 23876610. Leal WS. Odorant reception in insects: roles of receptors, binding proteins, and degrading enzymes. Annu Rev Entomol. 2013;58:373-91. doi: 10.1146/annurev-ento-120811-153635. Epub 2012 Sep 27. Review. PubMed PMID: 23020622 Xu P, Garczynski SF, Atungulu E, Syed Z, Choo YM, Vidal DM, Zitelli CH, Leal WS. Moth sex pheromone receptors and deceitful parapheromones. PLoS One. 2012;7(7):e41653. doi: 10.1371/journal.pone.0041653. Epub 2012 Jul 20. PubMed PMID: 22911835; PubMed Central PMCID: PMC3401280. Xu P, Hooper AM, Pickett JA, Leal WS. Specificity determinants of the silkworm moth sex pheromone. PLoS One. 2012;7(9):e44190. doi: 10.1371/journal.pone.0044190. Epub 2012 Sep 5. PubMed PMID: 22957053; PubMed Central PMCID: PMC3434217 Eliyahua, D., S. Nojimaa, R. G. Santangelo, S. Carpenterc, F. X. Webster, D. J. Kiemle, C. Gemeno, W. S. Leal, and Coby Schal. 2012. Unusual macrocyclic lactone sex pheromone of Parcoblatta lata, a primary food source of the endangered red-cockaded woodpecker. Proc. Natl. Acad. Sci. USA, doi: 10.1073/pnas.1111748109 Syed, Z., and W. S. Leal. 2011. Electrophysiological measurements from a moth olfactory system. J. Vis. Exp., doi: 10.3791/2489, 2011 E. Michel, F. F. Damberger, Y. Ishida, F. Fiorito, D. Lee, W. S. Leal, and K. Wuthrich. 2011. Dynamic conformational equilibria in the physiological function of the Bombyx mori pheromone-binding protein. J. Mol. Biol.,vol. 408, pp.922-931,,doi:10.1016/j.jmb.2011.03.008 Mao, Y., X. Xu, W. Xu, Y. Ishida, W. S. Leal, J. B. Ames, and J. Clardy. 2010. Crystal and solution structures of an odorant-binding protein from the southern house mosquito complexed with an oviposition pheromone. Proc. Natl. Acad. Sci. USA, doi: 10.1073/pnas.1012274107 Leal WS. Behavioural neurobiology: The treacherous scent of a human. Nature. 2010 Mar 4;464(7285):37-8. doi: 10.1038/464037a. PubMed PMID: 20203594 Syed, Z., A. Kopp, D. A. Kimbrell, and W. S. Leal. 2010. Bombykol receptors in the silkworm moth and the fruit fly. Proc. Natl. Acad. Sci. USA, vol. 107, pp. 9436-9439, 2010. Syed, Z., and W. S. Leal. 2009. Acute olfactory response of Culex mosquitoes to a human- and bird-derived attractant. Proc. Natl. Acad. Sci. USA, vol. 106, pp. 18803-18808, 2009. Syed, Z. and W. S. Leal. 2008. Mosquitoes smell and avoid the insect repellent DEET. Proc. Natl. Acad. Sci. USA, 105:13598-13603. http://www.pnas.org/content/105/36/13598.full.pdf Wogulis, M., T. I. Morgan, Y. Ishida, W. S. Leal, and D. K. Wilson. The crystal structure of an odorant binding protein from Anopheles gambiae: Evidence for a common ligand release mechanism. Biochem. Biophys. Res. Commun. 339: 157-164, 2006. Leal, W. S., R. M. R. Barbosa, W. Xu, Y. Ishida, Z. Syed, N. Latte, A. M. Chen, T. I. Morgan, A. J. Cornel, and A. Furtado. 2008. Reverse and conventional chemical ecology approaches for the development of oviposition attractants for Culex mosquitoes. PLoS ONE, 3(8): e3045. doi:10.1371/journal.pone.0003045. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003045 Ishida, Y. and W. S. Leal. 2008. Chiral discrimination of the Japanese beetle sex pheromone and a behavioral antagonist by a pheromone-degrading enzyme. Proc. Natl. Acad. Sci. USA 105: 9076-9080. http://www.pnas.org/content/105/26/9076.full.pdf Syed, Z., and W. S. Leal. 2007. Maxillary Palps Are Broad Spectrum Odorant Detectors in Culex quinquefasciatus. Chem. Senses 32:727–738. Syed, Z., Y. Ishida, K. Taylor, D. A. Kimbrell and W. S. Leal. 2006. Pheromone reception in fruit flies expressing a moth’s odorant receptor. Proc. Natl. Acad. Sci. USA 103:16538-16543. http://www.pnas.org/content/103/44/16538.full.pdf Ishida, Y. and W. S. Leal. 2005. Rapid inactivation of a moth pheromone. Proc. Natl. Acad. Sci. USA 102:14075-14079. PNAS Cover Article: http://www.pnas.org/content/102/39/14075.full.pdf Leal, W. S., A. M. Chen, Y. Ishida, V. P. Chiang, M. L. Erickson, T. I. Morgan, and J. M. Tsuruda. 2005. Kinetics and molecular properties of pheromone binding and release. Proc. Natl. Acad. Sci. USA 102:5386-5391. http://www.pnas.org/content/102/15/5386.full.pdf