The goal of this NRSA proposal is to use new approaches to further investigate the role of lipid signaling in olfactory signal transduction. Recent findings have rekindled interest in the possible involvement of phospholipid signaling in vertebrate olfactory transduction. The research project builds on indirect evidence from previous studies that the phospholipid substrates and products of phosphoinositide 3-kinase (PI3K) metabolism may play a role in olfactory transduction. The hypothesis to be tested is that specific phospholipid levels are rapidly and transiently changed in olfactory receptor neurons (ORNs) as the result of odor-dependent activation of PI3K. The proposed strategy is to characterize the PI3K(s) expressed in ORNs and assess PI3K activation by monitoring odor-evoked changes in the levels of two PI3K dependent phospholipids, PIP2 and PIPS, first in an established invertebrate animal model, and then to extend the results to mammalian ORNs. If, as preliminary findings suggest, PI3K signaling inhibits the output of mammalian ORNs in an odor-specific manner, the proposed research project has the potential to make a fundamental contribution to our understanding of the sense of smell. It could establish a cellular substrate for a bipolar basis to coding olfactory information and aid in explaining how odors not only excite but also inhibit ORNs. By creating a more complete understanding of the signaling pathways involved in the response to odors, this project will further elucidate both the normal and dysfunctional olfactory processes that are important to our quality of life and health.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DC009730-02
Application #
7681088
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Cyr, Janet
Project Start
2008-12-01
Project End
2011-11-30
Budget Start
2009-12-01
Budget End
2010-11-30
Support Year
2
Fiscal Year
2010
Total Cost
$52,154
Indirect Cost
Name
University of Florida
Department
Type
Organized Research Units
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Corey, Elizabeth A; Bobkov, Yuriy; Ukhanov, Kirill et al. (2013) Ionotropic crustacean olfactory receptors. PLoS One 8:e60551
Ukhanov, Kirill; Brunert, Daniela; Corey, Elizabeth A et al. (2011) Phosphoinositide 3-kinase-dependent antagonism in mammalian olfactory receptor neurons. J Neurosci 31:273-80
Ukhanov, Kirill; Corey, Elizabeth A; Brunert, Daniela et al. (2010) Inhibitory odorant signaling in Mammalian olfactory receptor neurons. J Neurophysiol 103:1114-22
Klasen, K; Corey, E A; Kuck, F et al. (2010) Odorant-stimulated phosphoinositide signaling in mammalian olfactory receptor neurons. Cell Signal 22:150-7
Brunert, Daniela; Klasen, Katharina; Corey, Elizabeth A et al. (2010) PI3Kgamma-dependent signaling in mouse olfactory receptor neurons. Chem Senses 35:301-8
Corey, Elizabeth A; Bobkov, Yuriy; Pezier, Adeline et al. (2010) Phosphoinositide 3-kinase mediated signaling in lobster olfactory receptor neurons. J Neurochem 113:341-50