18. GOALS FOR FELLOWSHIP TRAINING AND CAREER For my career in academic science, I hope to combine electrophysiology with computational techniques to study olfactory physiology. I would like to work as part of an interdisciplinary team that includes scientists with skills in complementary techniques, such as molecular biology, bioinformatics, and clinical science. This integrated approach will help to understand how alterations in sensory neurons influence network phenomena in the cortex or other physiological systems, or vice versa. The experiments outlined in this proposal integrate biophysical models with electrophysiology. Combining these techniques will help me develop the tools for integrating different approaches to test hypotheses. I have already used in vivo recording techniques in my current lab to study EOGs in mouse epithelium. We are using data from these experiments and histological experiments to study ion transporters. I will also learn to do whole cell and in vivo recording techniques during my training. The previous research experience I have in behavioral lmurophannacology, structural biology, biophysical chemistry, and molecular biology, in addition to the techniques I am learning in Dr. Steve Kleene's lab will prepare me for studying sensory physiology in an interdisciplinary team. SPONSOR 19. NAME AND DEGREE(S) Kleene= Steven J. 20. POSITION/RANK Associate Professor 21. RESEARCHINTERESTS_REAS I study the mechanisms of olfactory transduction in frog, mouse, and nematode. The primary method is electrical recording from single receptor neurons. RESEARCH PROPOSAL 22. DESCRIPTION (Do not exceed space provided) The goal of this proposal is to determine ion channel localization and Ca2+ buffering capacity of the cilia of olfactory neurons. Ion channels often have spatial arrangements within compartments of sensory neurons that dictate their timing and degree of activation. Olfactory neurons have narrow extensions called cilia, which contain a high density of ion channels. These ion channels, the cyclic-nucleotide-gated (CNG) channel, and the Ca2+-activated C1- channel, are activated sequentially during an odor response. Ca 2+from the CNG channel activates the C1- channel. The distribution of the two channel types in the ciliary membrane may dictate their relative timing of activation. It may also influence the amplitude of the response for the neuron, as a signal from the distal region of the cilium may diminish before it reaches the dendrite. Ca2+ buffering regulates processes in other sensory neurons by limiting the rate and range of Ca 2 diffusion from Ca2+ channels. In olfactory neurons, spatial arrangements and Ca2+ buffering may introduce a threshold CNG current for amplification. A biophysical model wiUbe used to make predictions about these two properties of the cilium. These predictions will be tested with patch clamp experiments. PHS 416-1 (Rev. 12/98) Form Page 2 BB CC Individual NRSA Application NAME (Last, first, middle initial) Table of Contents ========================================Section End===========================================
| Flannery, Richard J; French, Donald A; Kleene, Steven J (2006) Clustering of cyclic-nucleotide-gated channels in olfactory cilia. Biophys J 91:179-88 |
| French, Donald A; Flannery, Richard J; Groetsch, Charles W et al. (2006) Numerical Approximation of Solutions of a Nonlinear Inverse Problem Arising in Olfaction Experimentation. Math Comput Model 43:945-956 |
