DESCRIPTION (provided by applicant): The long-term goal of this project is to elucidate the function of aquaporin water channels in Drosophila melanogaster. The specific aims of this grant application are to: 1) Use mRNA in situ and immunohistochemistry to uncover the sites of action of putative aquaporins. 2) Determine the substrate specificity and pore permeability of putative Drosophila aquaporins. This will be accomplished by using the yeast vesicle expression system and stopped-flow fluorometry pioneered in the Brodsky and Zeidel laboratories and, if necessary, the more traditional Xenopus laevis egg-swelling assay. To further correlate function with location, in the future, loss of function alleles will be generated for candidates showing physiologically relevant water permeability and localization. Malpighian tubules from these flies will be tested in established water excretion assays. This work will further our understanding of the structure/function relationship for water channels, as well as our understanding of aquaporin function in maintaining osmotic homeostasis. This work is relevant not only to studies of mammalian renal function and Diabetes insipidus, but it will also help us understand insect water excretion, a prime target for controlling mosquito populations and the spread of malaria.