The long-term goal of this project is to explain the logic by which chemical signals are encoded, and to elucidate basic principles of the organization and development of the neurons that encode them. The experimental plan takes advantage of the fruit fly Drosophila melanogaster as a model system, which allows incisive molecular genetic analysis of chemosensory genes as well as physiological and behavioral analysis of chemosensory function. The project investigates a new family of 30 predicted chemoreceptor genes, the IR20a family, whose expression and function are completely unexplored.
The first aim i s to map these genes to neurons of chemosensory organs in the adult fly, and to examine their projections in the central nervous system.
The aim i s designed to address a major problem in sensory biology: how a sensory system integrates the multiple inputs that are ultimately translated into a behavioral response. A likely outcome of this aim is that it will support the identity of the IR20a family as a major new family of invertebrate taste receptors.
The second aim i s to produce a receptor-to-neuron map in the larval stage. The coexpression of these receptors with each other and with other classes of chemoreceptors will be analyzed. Their developmental profile and cellular location of expression in neurons will be determined.
This aim i s expected to support the identity of these receptors as a major new family of larval taste receptors.
The third aim tests the function of these receptors directly. Hypotheses concerning roles in chemoreception and in neuronal development will be tested through physiological and behavioral measurements, and by examination of neuronal morphology and projections. A model in which they play a dual role in the regulation of feeding will be tested. The molecular and cellular basis of feeding regulation has major implications for public health. Diseases carried by insects afflict hundreds of millions of people each year, and many of these insects locate their human hosts and their mates through chemosensory cues. Advances in the understanding of chemosensory reception may lead to new means of controlling these insect vectors of human disease.

Public Health Relevance

Insects transmit disease to hundreds of millions of people each year, and many insect vectors of disease identify humans through their chemosensory systems. This project is designed to reveal basic principles of insect chemosensation and could be useful in developing new means of preventing insects from identifying humans. The project also concerns the molecular and cellular basis of a decision, whether to accept or reject a potential food source, which is made by all animals and which has important implications for public health.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
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Sullivan, Susan L
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Yale University
Schools of Arts and Sciences
New Haven
United States
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Sun, Jennifer S; Larter, Nikki K; Chahda, J Sebastian et al. (2018) Humidity response depends on the small soluble protein Obp59a in Drosophila. Elife 7:
Park, Joori; Carlson, John R (2018) Physiological responses of the Drosophila labellum to amino acids. J Neurogenet 32:27-36
He, Zhe; Carlson, John R (2017) Molecules That Can Rewire the Taste System. Biochemistry 56:6075-6076
Delventhal, R; Menuz, K; Joseph, R et al. (2017) The taste response to ammonia in Drosophila. Sci Rep 7:43754
Joseph, Ryan M; Sun, Jennifer S; Tam, Edric et al. (2017) A receptor and neuron that activate a circuit limiting sucrose consumption. Elife 6:
Delventhal, Rebecca; Carlson, John R (2016) Bitter taste receptors confer diverse functions to neurons. Elife 5:
Stewart, Shannon; Koh, Tong-Wey; Ghosh, Arpan C et al. (2015) Candidate ionotropic taste receptors in the Drosophila larva. Proc Natl Acad Sci U S A 112:4195-201
Joseph, Ryan M; Carlson, John R (2015) Drosophila Chemoreceptors: A Molecular Interface Between the Chemical World and the Brain. Trends Genet 31:683-695
Kwon, Jae Young; Dahanukar, Anupama; Weiss, Linnea A et al. (2014) A map of taste neuron projections in the Drosophila CNS. J Biosci 39:565-74
Koh, Tong-Wey; He, Zhe; Gorur-Shandilya, Srinivas et al. (2014) The Drosophila IR20a clade of ionotropic receptors are candidate taste and pheromone receptors. Neuron 83:850-65

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