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Barry W Ache

Distinguished Professor/Whitney Faculty
Ph.D. University of California, Santa Barbara, 1970

Whitney Marine Lab
Personal Website

Research Interests

Chemical Senses: Olfaction Our research group studies olfaction – the sense of smell. Natural odors are complex blends of chemicals that the brain discriminates by the unique pattern of neural activity each odor generates. We are trying to decipher the cellular and neural processes that give rise to these patterns in order to ultimately understand how the brain recognizes and discriminates odors. We investigate the sense of smell by studying animal models for olfaction as diverse as spiny lobsters and rodents.

Current Projects

Research in our group centers around two primary projects that are linked, ultimately, to odor coding. Our longest-running project, funded by the National Institute on Deafness and Other Communication Disorders, explores the cellular events by which odors activate lobster olfactory receptor cells. The general focus of this project is to understand the involvement of lipid signaling in olfactory transduction. Olfactory transduction is the process by which the receptor cell converts odor signals into the electrical signal the brain uses to process information. In particular, we are focusing on a family of ion channels, called trp channels that typically serve as the intracellular target of the phosphoinositide signaling pathway. Trp channels are increasingly implicated in chemosensory transduction, but the extent of their involvement in olfactory transduction is still unclear with the notable exception of the lobster. We are using lobster olfactory receptor cells as models to understand for the first time how trp channels can function in olfactory transduction. Much of what we know of trp channels in other systems comes from studying recombinant trp channels in non-native or heterologous cells. Our work to date has made the lobster olfactory trp channel one of the best characterized native trp channels. This work has the potential to contribute to a broader understanding of this functionally important class of ion channels as well as advance our understanding of the cellular mechanism of olfactory transduction.

Our newer project, also funded by the National Institute on Deafness and other Communication Disorders, explores the role of phospholipid signaling in mammalian olfactory transduction. In particular, we are focusing on how a specialized group of membrane lipids, collectively known as 3-phosphoinositides, modulate the output of mammalian olfactory receptor cells, which they appear to do at least in part by targeting the well known olfactory cyclic nucleotide-gated ion channel. This project grew out of our work with lobster olfactory receptor cells that showed for the first time that 3-phosphoinositides are potentially important in olfactory transduction. Problems with any of the cellular events associated with olfactory receptor cell activation would disrupt normal input, and necessarily lead to olfactory impairment. Therefore, the more detailed understanding we have of these processes, the more effectively we can address the diminished quality of life that results from olfactory dysfunction. This project is an excellent example of the utility of marine biomedical research - how research on a marine animal can generate information of potential usefulness to understanding human health.

Representative Publications

Spehr, M., Wetzel, C.H., Hatt, H., and Ache, B.W. 2002. 3-phosphoinositides modulate cyclic nucleotide signaling in olfactory receptor neurons. Neuron 33:731-739.

Bobkov, YV and Ache, BW. 2003. Calcium sensitivity of a sodium-activated nonselective cation channel in lobster olfactory receptor neurons. J. Neurophysiol. 90:2928-2940.

Zhainazarov, A.B., Spehr, M., Wetzel, C.H., Hatt, H., and Ache, B.W. 2004. Modulation of the olfactory CNG channel by PtdIns (3,4,5)P3. J. Memb. Biol. 201:51-57.

Bobkov, Y.V. and Ache, B.W. 2005. Pharmacological properties and functional role of a TRP-related ion channel in lobster olfactory receptor neurons. J. Neurophysiol. 93:1327-1380.

Ache, B.W. and Young, J.M. 2005. Olfaction: diverse species, conserved principles. Neuron 48:417-430.

McClintock, T.S., Ache, B. W., Derby, C.D. 2006. Lobster olfactory genomics. Integr. Comp. Biol. 46: 940-947.

Bobkov, Y.V. and Ache B.W. 2007. Block by amiloride derivatives of odor-evoked discharge in lobster olfactory receptor neurons through action on a presumptive TRP channel. Chem. Senses32:149-159.

Bobkov, Y.V. and Ache, B.W. 2007. Intrinsically bursting olfactory receptor neurons. J. Neurophysiol. 97:1052-1057.