Elucidating mechanisms of carbon dioxide detection in insects

Project Summary/Abstract Both a driver of climate change and an ingredient in bubbly drinks, carbon dioxide is a small, volatile gas imperceptible to humans. Many insect species, however, possess specialized receptors capable of sensing changes in carbon dioxide levels in their environment. Behavioral responses to carbon dioxide vary significantly based on species and context. For instance, bees utilize elevated carbon dioxide levels as a signal to flap their wings to ventilate their hives whereas flies avoid the gas unless searching for a food source. Additionally, a number of disease-carrying insects such as Anopheles gambiae (malaria), Aedes aegypti (yellow fever and dengue virus), and tsetse flies (sleeping sickness) use carbon dioxide as a cue for host detection. Carbon dioxide sensing is critical for many insect species, yet the underlying molecular mechanisms are not fully understood. Individual receptor subunits have been identified but their contributions to ligand recognition and channel gating remain unclear. Uncovering the mechanisms of host carbon dioxide detection would allow for the development of novel antiviral strategies against some of the world's deadliest diseases. The proposed project aims to determine the molecular basis underlying carbon dioxide detection through three aims. In aim 1, we will determine how to express and purify carbon dioxide receptors. In aim 2, we will obtain a structure of the Aedes aegypti carbon dioxide receptor and finally in aim 3, we will compare ligand binding pockets of two species, Aedes aegypti and Drosophila melanogaster. By understanding species-specific binding pocket differences, we can develop compounds that target the receptors of disease-carrying insects with high specificity. Together, these three aims will establish the molecular mechanisms underlying carbon dioxide detection and widen strategies for combating vector-borne diseases.