Investigation of the role of candidate genes in Drosophila melanogaster immunity by an in vivo RNAi screen -

Abstract

Drosophila is an excellent model organism to genetically dissect innate immune pathways without interference from the adaptive responses since insects lack adaptive immunity. The abundant genetic tools available for this model are also a major advantage, and the recent expansion of RNAi techniques and the availability of transgenic flies that express hairpin constructs via the UAS-Gal4 system allow for the knockdown of any gene in a spatially and temporally controlled manner. The humoral response is an important component of fly immune defenses; it includes melanization and the synthesis by the fat body of antimicrobial peptides whose expression is controlled by two main pathways: Toll and Imd. Previous studies have identified a number of genes that are upregulated at the transcriptional level after immune challenge. Several of these genes are of unknown function and do not have clear characterized orthologues in other species. On the other hand, among the induced genes that have a putative attributed function, the Serpin family is well represented. Some serpins have been shown to act as serine-protease inhibitors upstream of the Toll pathway and others as negative regulators of melanization cascades. Using an in vivo RNAi screen, this proposal aims at investigating the potential involvement of some of the serpins that have not been previously analyzed and of the unknown candidate genes in Drosophila melanogaster defenses.