Recent advances in biotechnology have led to the acquisition and interpretation of large scale gene expression data. Scientific progress in developmental biology as well as improved understanding of genetically based diseases are impossible without efficient methods for the processing and interpretation of this information. This proposal addresses these problems by the application of both computational and mathematical methods to the dynamics of gene expression in the Drosophila segment determination system. The specific aims of the project are to use computational methods to synthesize quantitative data from individual embryos into an integrated quantitative atlas of segmentation gene expression at cellular resolution and to design a precise clock for staging embryos based on segmentation gene expression. We will develop an atlas (searchable database) of segmentation gene expression at cellular resolution that will be accessible over the Internet. Mathematical methods will be used to interpret the expression data with the ultimate goal to understanding the functional interactions of genes controlling segmentation in Drosophila in terms of a coarse-grained chemical kinetic model. Specifically, statistical analysis methods and simulations of the segmentation process in 2D space will be applied. In addition we will find exact and asymptotic solutions of the highly nonlinear coupled reaction-diffusion equations that describe the segment determination process. The project is a natural extension of the activity supported by the NIH grant RR-07801 and will result in significant advances in understanding of the architecture and function of the segmentation system.

R03TW001147

1999-09-30

2003-08-31