Abstract
The epizootic caused by the Atlantic salmon louse, a caligid ectoparasitic crustacean, is a severe threat to wild and domestic salmonids. Novel therapeutic approaches to dealing with this pest are needed. Exposure of the louse to freshwater rapidly breaks down its semi-adaptive homeostasis highlighting the osmoregulatory systems for potential therapeutic action. During ecdysis, the louse swells almost exclusively with water, suggesting that disruption of water transport mechanisms can expose an untapped vulnerabilty. The cellular mechanisms that underlie the growth and water homeostasis of the louse are, however, virtually unknown. Aquaporins are major targets for drug discovery in biomedical research, and have recently gained ground in the fight against malaria where channel disruption increases the host´s resistance to infection. By targeting the adaptive channel transport systems of the louse in relation to its vertebrate host, we aim to generate an avenue for differentially regulating aquaporins as a potential means of prophilaxis. Using a heterologous Xenopus oocyte system, structural and functional data will be obtained to determine channel solute selectivity of host and parasite aquaporins. Knock-down experiments in the louse using RNAi technology will be applied to decipher the phenotypic effects on its osmotic physiology, growth and differentiation. Potential chemotherapeutants will be tested to screen for differential disruptors of the louse rather than the host aquaporins. Crystallographic data will be generated to determine critical residues associated with the channel architecture and site-directed mutagenesis used to validate the structure-function relationships. We further aim to validate our hypothesis that aquaporin evolution was fundamentally associated with animal radiation during the Devonian Period. The project thus provides an exciting combination of molecular genetics, evolution, and potential drug targeting of invertebrate aquaporins.
Norway