Yale scientists have discovered that the key to tackling many public health and agricultural problems may lie in understanding the fruit fly’s sense of smell.
John Carlson, a professor of molecular, cellular and developmental biology, and his former student, Elissa Hallem GRD ’05, have plotted the entire Drosophila olfactory system. Their findings, which were published in the journal Cell, resulted in the first multidimensional map to mark the positions of odor receptors and the corresponding regions they stimulate in the fly’s brain.
The study followed an investigation of the molecular basis of odor detection and discrimination in insects through analysis of the receptor proteins that bind to the odors and send signals to the brain. Carlson said the purpose of the project was threefold: to investigate how insects find humans and plants, to learn how this applies to the way the nervous system works, and to determine the consequences of the research for human beings.
Carlson said insect olfaction is important to human beings because of the prevalence of insect-transmitted diseases such as malaria, West Nile virus and African sleeping sickness.
“A lot of what we’ve found applies to humans,” he said. “About 30 percent of the people on the planet are affected by diseases carried by insects. And insects find their human hosts through their sense of smell.”
Carlson said his findings also have implications for the agricultural industry because insects use their sense of smell as a tool to locate and damage plants.
Robert Anholt, a professor of zoology and genetics at North Carolina State University, said Carlson’s work is not only important to humans but to the animal kingdom as well.
“The ability to respond to chemical signals from the environment is essential for the survival and procreation of most animals,” he said.
The study allowed Carson and Hallem, who is now conducting postdoctoral research at the California Institute of Technology, to make predictions about which odors smell alike to the fruit fly. To do this, the two studied how the fruit fly’s olfactory system responded to more than 100 different odors, some synthetically created and others found in natural food sources, such as fruit.
“Some of the odors we tested smell very similar to humans, and some smell very different,” Hallem said. “We found that different odors are represented very differently by the fly’s olfactory system, both in terms of which olfactory receptors are excited or inhibited by a particular odor, and also in terms of how long the response lasts.”
Hallem said that with their data she and Carson could predict that odors that have similar patters of receptor activation will smell more similar than odors that elicit very different patterns.
After making these predictions and creating this model of the Drosophila olfactory system, Carlson said they tested their predictions on a group of Yale students and faculty by giving them a set of three odors and asking them to identify which one was most different. Based on this test, the predictions made based on their model were correct, Carlson said. The model showed that there is a whole continuum of receptors that range from being narrowly tuned to broadly tuned, he said.
“The results were consistent with a model in which the brain can figure out which odors are out there,” he said.
Carlson said one surprising result of the study was the importance of inhibition of receptors, as opposed to excitation.
“Most odors inhibited at least one receptor, and most receptors are inhibited by at least one odor,” he said. “This makes it easier for the olfactory system to encode an odor and easier to send signals to brain to identify because it doubles the number of signals the receptors can send to the brain.”
Hallem said she hopes her work with Drosophila will both increase the understanding of insect olfactory systems and translate into positive and practical uses for human beings.
“Some of the insight we gain into how insect olfactory systems work will hopefully be useful in designing better insect traps and repellents for insect pests and disease vectors,” she said.
Anholt said Carlson’s efforts have made the Drosophila olfactory system the best and most completely characterized olfactory system.
“[Carlson’s efforts have] generated broadly applicable insights in how a simple nervous system enables an organism to view its chemosensory world with a great degree of sophistication,” he said.