Physiological Model of Gene Regulation in Drosophila

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DESCRIPTION (provided by applicant): Networks of interacting genes control a variety of fundamental biological processes, including embryonic development, cell division, and cell death. Understanding the function of an entire network of genes that control development is a central problem of functional genomics. Although general technology to solve the problem does not yet exist, it can be solved today for the network of genes that control the segmentation system of Drosophila melanogaster. Our research design consists of an integrated program of experimentation and computational modeling, which we will use to characterize the process by which positional information encoded in maternal gradients is transformed into precise and stable expression of the segment polarity genes engrailed (en) and wingless (em wg) in stripes one nucleus in width. The work proposed will result in a realistic and predictive description of pattern formation in morphogenetic field at the level of coarse-grained chemical kinetics. Our specific aims are to 1) Construct a chemical kinetic model describing the evolution of the expression patterns of the segmentation genes from maternal gradients to stripes of wg and en expression. 2) Use this model to precisely understand how each expression domain of every segmentation gene forms where and when it does. To make our data and tools widely available, we propose to 3) Complete the construction of, and make publicly available on the web, a quantitative database of segmentation gene expression at cellular resolution and a simulation application server.