Classic genetic approaches in Drosophila can also be applied to probing structure-function relationships of toxins or other virulence factors. One straightforward approach to define domains of a toxin that are important for producing the phenotype of interest is to mutagenize flies carrying a UAS-toxin construct and to screen for loss of the phenotype that results from expression of the wild-type toxin (Fig. 3E ). One can then PCR amplify the mutated UAStransgenes and sequence the putative mutant allele to determine the molecular nature of the loss-of-function mutation. It is also possible to screen for mutations in the transgene that results in altered phenotypes caused by dominant gain-of-function mutations (Guichard et al., 2002) .