The goal of the research outlined in this application is to utilize genomics technologies to study complex developmental process. It is proposed to use the fruit fly Drosophila melanogaster as a model organism in this regard. Most significant to human health is the potential application of the approach described here to the study of complex diseases. Also of significance to human health will be the identification of new molecules in genetic pathways that are conserved between Drosophila and humans. Specifically, it is the aim of the proposed research to provide an experimental basis for understanding how networks of genes work together during drosophila development. This goal will be accomplished by using two related technologies. The first is gene expression DNA microarray, where the expression profiles of thousands of genes will be monitored simultaneously in wild type animals. In the Research DNA microarrays containing almost all of the gens in the Drosophila genome. In the Faculty Transition phase this work will be continued, analyzing other stages of the life cycle. Individual tissues, specifically the developing wing, will be included in the analyzes in order to derive spatial as well as temporal information about global patterns of gene expression. The second technology to be utilized is genotyping DNA microarrays, which will be used to map genetic variation that corresponds to phenotypic variation. This technology will be useful for assessing the effect of genetic variation on Drosophila development. Again, the wing will be used as a model for the application of genome-wide genotyping in the analysis of molecular genetic variation linked to morphological variation. This technology and general approach also will be potentially useful for assessing the role of genetic variation in human disease. During the Research Scholar phase this technology will be developed. During the Faculty transition phase it will be used to map loci that are responsible for wing morphology variation. Combining information from genome-wide expression and genetic mapping will result in a better understanding of gene genes and their products work together to produce complex phenotypes.
