| dc.description.abstract | Inward rectifier potassium (Kir) channels are a family of two transmembrane-spanning potassium selective ion channels. Kir channels are found in all kingdoms of life where they play essential roles in regulating numerous physiological functions. Mutations affecting Kir channels result in various diseases ranging from cardiac, neurological, renal and metabolic defects. Therefore, Kir channels represent important therapeutic targets. However, the Kir channel small-molecule pharmacology remains limited, which has impeded progress toward understanding their integral physiology and druggability. Since the emergence of insecticide-resistance in mosquito populations against current vector control agents, such as pyrethroids, efforts to decrease the transmission of vector-borne diseases are becoming less efficacious. As a result, we are facing a critical need for novel control agents. In mosquitoes, Kir channel functions remain largely unknown and their insecticidal potential unexplored. In an effort to expand the small-molecule pharmacology of Kir channels, we employed a broad array of experimental techniques, including molecular biology, fluorescence-based high-throughput screening, conventional and automated patch clamp electrophysiology, in conjunction with medicinal chemistry and mosquito bioassays to discover, optimize and characterize new modulators of Kir channel functions for the development of new therapeutics and insecticides. | |
