Physiological Model of Gene Regulation in Drosophila

描述(申请人提供)：相互作用的基因控制网络 各种基本的生物过程，包括胚胎发育， 细胞分裂和细胞死亡。了解整个网络的功能 控制发育的基因是功能基因组学的中心问题。 虽然目前还不存在解决问题的通用技术，但它可以 今天为控制基因分割系统的基因网络而解决 黑腹果蝇。我们的研究设计包括一个完整的计划 实验和计算模型，我们将用它们来 描述位置信息在母体中编码的过程 将梯度变换为精确、稳定的分段表达 带(En)和无翼(Em Wg)的极性基因在一个核的条纹中 宽度。建议的工作将产生一个现实的和预测性的描述 粗晶水平上形态发生场中花纹形成的研究 化学动力学。 我们的具体目标是：1)建立一个化学动力学模型 母本基因片段表达模式的进化 渐变到WG和EN表达的条纹。2)使用该模型精确地 了解每个片段基因的每个表达区域是如何在哪里形成的 当它发生的时候。为了让我们的数据和工具广泛可用，我们建议3) 完成构建，并在Web上公开提供 细胞分辨率的分割基因表达的定量数据库 和仿真应用服务器。

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.