Genetic screens for recessive lethal embryonic mutations and for adult phenotypes using the FLP/FRT system to generate genetic mosaics have formed the basis of much of our understanding of Drosophila developmental genetics. Although these techniques have facilitated the discovery of many genes involved in development, what is not possible using any of the techniques available today is to efficiently screen for synthetic lethality or synthetic interactions between mutations with recessive phenotypes.
We aim to establish a set of new genetic tools that will make it possible to efficiently screen for synthetic interactions in Drosophila. Screening for synthetic interactions requires the use of two independent genetic recombination systems to generate single and double mutant clones within one animal. This proposal aims at establishing a second site-specific recombination system, the fC31-integrase/att system, in Drosophila. Combined with the FLP/FRT system, the fC31-integrase/att system will perform efficient screens for synthetic interactions. We will test this system in flies using mutations in the components of the Insulin Receptor (InR) signaling pathway (PTEN, InR, and dAM). These tools will have broad applications and will lead to the discovery of novel genetic interactions in Drosophila that could not have been detected using currently available methods. ? ? ?
