We are interested in the molecular mechanisms underlying chemosensation (taste and smell) in mammals. The receptors that detect odorants, pheromones, and many tastants including bitter and sweet chemicals are G-protein coupled receptors (GPCRs), which typically have seven transmembrane domains. There are many important questions that are still unanswered in chemosensory neurobiology. How do tens of thousands of different chemicals (tastants, odorants, or pheromones) interact with more than one thousand chemosensory receptors (about 1000 odorant receptors, 40 taste receptors and 200 vomeronasal receptors in the case of mice or rats)? How is the information coded in sensory cells and in the brain? How does the brain direct appropriate behavioral responses? What are the mechanisms underlying development and regeneration of sensory cells and specific synapse connections? We address these questions using molecular biology, genome information and genetics.
The detection of tastants is mediated by taste receptor cells that are clustered in taste buds in the mouth. Interestingly, some people can taste certain chemicals, such as 6-n-propylthiouracil (a bitter compound) while others can't. Likewise, some strains of mice can taste certain bitter or sweet tastants while others can't. Based on these variations, the bitter and sweet taste loci have been mapped on human or mouse chromosomes. By using the increasingly powerful genome informatics tools, we as well as other groups, have identified families of GPCRs that may detect bitter and sweet compounds. We seek to understand how specific changes in nucleotide sequences cause these differences in taste sensitivity. Another goal is to understand how the gustatory system is organized.
In olfaction, the detection of volatile odorants is mediated by olfactory sensory neurons in the olfactory epithelium of the nose. Odorants are detected by about 1000 different types of odorant receptors that are encoded by a multigene family. Each olfactory sensory neuron expresses only one receptor type out of 1000 receptors. Axons of neurons expressing the same receptor all converge in a few glomeruli in the olfactory bulb of the brain. We wish to understand the mechanisms underlying this convergence.
Finally, we are interested in the pheromone sensing system. Pheromones are chemicals that are released from animals and induce innate behavior, such as mating or aggression, or hormonal changes in members of the same species.
The detection of pheromones is mediated primarily by a second olfactory sense organ, called the vomeronasal organ (VNO). We, as well as other groups, have found families of candidate pheromone receptors by comparing gene expression between single VNO neurons. Pheromone molecules may induce their effects by activating some of these receptors, which ultimately affect particular regions of the brain. We seek to understand how these pheromonal effects are mediated.
Education and Training
- Kyoto University (Japan), Ph.D. 1996
Selected Grants and Awards
- Summer Scholars Program in Genome Sciences and Medicine
- Biogenesis of olfactory G protein-coupled receptors
- Training Program in Developmental and Stem Cell Biology
- High-throughput mapping of olfactory receptor identity to olfactory bulb glomeruli
- Genetics Training Grant
- Organization and Function of Cellular Structure
- Peripheral Odor Coding in Mammals
- Collaborative Research: Analysis of the Mammalian Olfactory Code
- US-France Research Proposal: Predicting odorant-dependent and independent olfactory neuron activation based on receptor
- Olfactory moding in mammals
- In vivo patterns of receptor activation by odorants
- Basic predoctoral training in neuroscience
- NSF sponsored conference
- BRAIN EAGER: Solving the Code of Olfaction Using Nano-Robot Switchable Odorants
- Building archaic hominin olfactory receptors: a functional approach to paleogenomes
- Modulation of Odorant Receptor Function
- Gene expression Profiling in Mammalian Taste Tissue
- Training in Fundamental &Translational Neuroscience
- Automated Library Preparation System for Next-Generation Sequencing
- Molecular Mechanisms Underlying Odorant Recognition
- Variability in the human odorant receptor repertoire
- The Genetic Basis of Specific Anosmia
- The in vivo roles of PKD1L3 and PKD2L1 in sour taste detection
- Molecular Mechanisms Underlying Specific Anosmia and Sensitization