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The olfactory system does two unique things: It detects odors and it replaces injured neurons by activating resident tissue-level stem cells, even in adults. My lab investigates the molecular physiology of both of these processes.
Odorant receptors comprise the largest gene family in mammals, with up to 1500 genes in some species, yet each olfactory sensory neuron expresses only one allele of one of these genes. We are investigating the mechanisms that underlie this amazing specificity, both the activation of the chosen allele/gene and the silencing of the remaining odorant receptor genes.
The process of neural replacement in the olfactory epithelial is a natural example of the therapeutic process that many envision as the future of treatment for neurodegenerative disorders and neurotrauma. We investigate the molecular and cellular mechanisms that control olfactory neurogenesis, such as the ability of transcription factors to control epigenetic mechanisms such as chromatin remodeling and genetic reprogramming.
Both of these projects are informed by the application of molecular systems biology to the olfactory system. In essence, we have developed approaches that are allowing us to map the expression of every gene in each of the cell types in the olfactory epithelium.
Technologically, we use physiological genomics techniques, such as microarrays, to observe system-wide effects and then use techniques focused on specific processes or genes, such as targeted gene deletion (gene knockout), electrophysiology, biochemistry, and anatomy to plumb the depths of regulatory networks of proteins controlling function. The mouse is our primary experimental model.
2010. Sammeta, N and TS McClintock. Chemical stress induces the unfolded protein response in olfactory sensory neurons. J. Comp. Neurol., 518:1825-1836.
2010. McClintock, TS, Achieving singularity in mammalian odorant receptor gene choice.
2008. McIntyre, JC, SC Bose, AJ Stromberg and TS McClintock. Emx2 stimulates odorant receptor gene expression. Chem. Senses, 33:825-837.
2008. McClintock, TS, CE Glasser, SC Bose, and DA Bergman. Tissue expression patterns identify mouse cilia genes. Physiol. Genomics, 32:198-206.
2007. Sammeta, N, T-T Yu,, SC Bose and TS McClintock. Mouse olfactory sensory neurons express 10,000 genes. J. Comp. Neurol. 502:1138-1156.
2006. Stepanyan, R, K Day, J Urban, DH Hardin, RS Shetty, CD Derby, BW Ache and TS McClintock. Gene expression and specificity in the mature zone of the lobster olfactory organ. Physiol Genomics, 25:224-233.
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