Animals detect multiple kinds of stimuli, including chemicals, force, light and temperature. Distinct sensory modalities often rely on related molecular receptors2. In some cases the same receptor participates in multiple sensory modalities. How does such polymodality emerge? How can it be regulated to enable sensory discrimination? We will probe these issues by studying two classes of polymodal receptors we have identified in the fruit fly Drosophila melanogaster whose polymodality is regulated by complementary molecular mechanisms. We propose to investigate these issues in three aims. 1) We will probe the molecular mechanisms by which the activity of a receptor for both moderate warming and aversive chemicals can be regulated in a cell-specific fashion to achieve appropriate sensitivity and specificity, and use these studies to investigate the molecular basis of thermal and chemical detection in both fruit flies and Anopheles mosquitoes. 2) We will investigate how a pair of receptors act together to mediate both thermosensation and hygrosensation, and how these distinct activities are regulated to confer appropriate behavioral responses to each stimulus in both fruit flies and Anopheles mosquitoes. 3) We will test the hypothesis that multiple related receptors can function together in a combinatorial fashion to create distinct classes of sensory receptors that mediate responses to distinct sensory modalities in different sensory neurons in both fruit flies and Anopheles mosquitoes. Together, these studies will provide fundamental insights into the molecular basis of sensory receptor polymodality, how sensory receptors detect thermal and chemical stimuli, and how sensory receptor activity can be regulated to achieve appropriate sensory sensitivity and specificity.
This proposal investigates the fundamental molecular mechanisms that regulate chemical and thermal sensation by examining the ability of sensory receptors to participate in multiple sensory modalities. The ability to sense and respond to chemicals (such as chemical repellents and moisture) and to temperature is critical for animal physiology, and the dysregulation of these sensory modalities can contribute to disease. In insects, the ability to sense temperature and humidity is important for host-seeking by insect vectors for widespread human diseases like malaria and dengue. Furthermore, the detection of chemical repellents is important for the action of vector control agents. Thus, the study of chemical and thermal sensation is of biomedical relevance.
|van Giesen, Lena; Garrity, Paul A (2017) More than meets the IR: the expanding roles of variant Ionotropic Glutamate Receptors in sensing odor, taste, temperature and moisture. F1000Res 6:1753|
|Knecht, Zachary A; Silbering, Ana F; Cruz, Joyner et al. (2017) Ionotropic Receptor-dependent moist and dry cells control hygrosensation in Drosophila. Elife 6:|
|Knecht, Zachary A; Silbering, Ana F; Ni, Lina et al. (2016) Distinct combinations of variant ionotropic glutamate receptors mediate thermosensation and hygrosensation in Drosophila. Elife 5:|