Genetic mechanisms of phenotypic variation within and amongst genotypes, environments, and sexes - PROJECT SUMMARY The laboratory studies how genetic variation, sex differences, and environmental heterogeneity affect phenotypic differences within and between species. Determining how genetic and environmental factors affect phenotypes—and how those effects differ between sexes—is essential for understanding the mechanistic basis of traits, including many human diseases. The laboratory’s current research has three primary areas of focus: the genetic basis of sex-specific cellular, physiological, and behavioral variation; sex chromosomes and sexually dimorphic gene expression; and the regulation of the immune response to bacterial infection. The goals for the next five years involve determining the genetic mechanisms responsible for phenotypic variation within and amongst genotypes, sexes, and environments. This research will address important gaps in our understanding of why there is phenotypic variance within genotypes, and how that variation relates to phenotypic differences across genotypes, sexes, and environments. The project will accomplish its goals by combining experimental and genomic approaches across multiple species that are informative of general principles because of their unique biological features or available genetic tools. Two of those species—house fly (Musca domestica) and Drosophila pseudoobscura—harbor natural genetic variation that will be used to determine how genotype, environment, and sex interact to affect phenotypes. A third species, Drosophila melanogaster, is a powerful model organism with a rich suite of genetic and genomic resources that will be used to determine the mechanistic basis of phenotypic variation. The project will use quantitative and population genomic approaches in all three species to measure how genotype, environment, and sex contribute phenotypic variation within and among individual organisms. Comparative and functional genomics approaches across these species and their close relatives will also be used to identify genes and regulatory networks that could underly phenotypic variation. Hypothesized mechanisms identified from the quantitative, population, comparative, and functional genomics analyses will be tested using the powerful D. melanogaster genetic toolkit. The laboratory is well-suited to perform this work because of its expertise using evolutionary and functional genomics approaches to study phenotypic and genetic variation within and across species.