Perception of tastes, odors and chemical irritants begins with the interaction of a chemical stimulus with specialized sensory receptor cells in the mouth, nose and skin. A cascade of molecular and cellular events then transduces information about the stimulus into electrical signals that can be recognized by the nervous system. Monell researchers pioneered the use of living human chemosensory tissue, including taste buds and olfactory receptor neurons cells, to study how human taste and smell receptors function.

Scientists in the Neuroscience and Molecular Biology Program use a combination of approaches— biochemical, biophysical, neurophysiological, molecular biological, and genetic— to characterize how tastes and smells are recognized, transduced, and processed in the brain.

Using recent advances in molecular genetics, Monell’s research is revealing how genes influence the chemical senses, from olfactory receptor function to sensitivity to different tastes, as well as the consequent influences on behavior and health.

Taste

The flavor of a food or beverage represents a complex integration of messages from taste, smell and chemical irritants. Taste detection starts in receptor cells, which are located in taste buds on the tongue, palate, and throat. Taste molecules primarily interact with receptor proteins on the receptor cell membrane. These receptor proteins are specific for one of the five taste qualities (sweet, sour, salty, bitter, umami). When stimulated by a taste molecule, the receptor proteins activate second messenger systems inside the cell to open ion channels in the cell membrace, ultimately causing the cell to fire and initiate a signal to the brain, where recognition of the taste occurs.

The taste bud, a key processing unit, is one focus of study at Monell. Taste responses are initially modulated and shaped by interactions among the different cells within a single taste bud. Monell scientists have imaged a human taste bud still within an intact papillae to observe the reaction of individual taste cells to stimulation by taste compounds.

Using molecular biological and molecular genetic techniques, Monell researchers recently identified several proteins from the taste bud that are critical in cell-to-cell interactive processing and the transduction process. Biochemical and biophysical studies are currently exploring the intracellular mechanisms that generate taste signals in the receptor cells.

With the recent discovery of genes involved in bitter taste and the sequencing of the entire human genome, scientists can now examine genes at the nucleotide level and correlate differences in DNA with a person’s taste sensitivity. Molecular genetics studies focus on the genetic basis of individual differences in taste and nutritional status. Center scientists are currently characterizing genes important in salty, bitter and sweet tastes, as well as genes that influence obesity and the preference for calcium and dietary fat.

Monell scientists recently discovered the presence of inflammatory receptors on membranes of many taste bud cells. This means that any condition resulting in chronic inflammation may have taste distortions as one of its symptoms. Such diseases as Lupus (autoimmune), upper respiratory infection, and even obesity,

Olfaction

The nose can detect an extraordinary range of odors. This high sensitivity and broad tuning are the result of the nose’s millions of receptor cells. Olfactory receptor cells are nerve cells that communicate directly with the brain.

Inside the nose, odorant molecules interact with receptor proteins located in cilia extending from the receptor cells. This activates the formation of so-called “second messengers,” which open ion channels in the cell membrane. Passage of ions through the open channels in turn generates nerve impulses in that are transmitted directly from the receptor cell to the olfactory bulbs in the brain.

Monell scientists are studying the initial steps in olfaction, the interaction of odor stimuli with the receptor nerve cell and the subsequent generation of signals through the olfactory bulb and into the deep regions of the brain.

Intricate processing and coding goes on at every level. One area of study focuses on cellular and synaptic mechanisms involved in the complex pathways that make up the micro-neural structure of the olfactory bulb. Other studies use computational and neuroimaging techniques for multi-level investigation of how odors are interpreted in the brain.

Individuals differ in their ability to perceive various odors; studies are revealing that some of these differences are genetically-based.

Irritation

Chemosensory irritation and pain serve as a warning system for damaging substances. Sensations of irritation, including pungency, cooling, itch and tingle, signal the presence of potentially harmful conditions. Monell scientists are furthering our understanding of the organization and function of the nerves that mediate irritating sensations.

Ongoing studies in Monell’s Neuroscience and Molecular Biology program include studies designed to:

• Characterize the pathways that mediate taste cell responses to different stimuli and their distribution among receptor cells
• Identify taste-specific proteins that play pivotal roles in taste transduction
• Uncover the molecular and cellular bases of genetic differences in sensitivity of different strains of mice to taste stimuli
• Use advanced microscopy to characterize the responses of human olfactory and taste receptor cells
• Determine the genetic basis of individual differences in taste and nutritional status
• Use computational models to predict the transport and deposition of odorants through the nasal cavity
• Identify the thresholds for activation of sensory neurons by various noxious compounds
• Develop cell culture systems to study nerve cells from the taste and smell systems under controlled conditions
• Use the distribution of olfactory receptors for different qualities on individual receptor neurons to unravel olfactory coding
• Identify genetic polymorphisms in taste receptor proteins that underlie individual differences in taste sensitivity, food choice and nutritional status
• Characterize the presence of inflammatory receptors on taste bud cells and the relevance to taste distortions in diseases characterized by chronic inflammation