Physiological Model of Gene Regulation in Drosophila

果蝇基因调控的生理模型

• 批准号: 7929841
• 负责人: John B. Reinitz
• 金额: $ 26.14万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7929841
• 关键词: Architecture; Behavior; Biochemical; Biological; Biological Assay; Biological Process; Biology; Blastoderm; Cell Death; Cell Nucleus; Cell division; Cells; Computer Simulation; Cues; Data; Data Set; Databases; Development; Developmental Process; Drosophila genus; Drosophila melanogaster; Embryo; Embryonic Development; Engineering; Event; Evolution; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genome; Genomics; Genotype; Goals; Heart; Individual; Internet; Laboratories; Management Information Systems; Metabolism; Methods; Modeling; Molecular; Morphogenesis; Noise; Pattern; Pattern Formation; Physiological; Population; Problem Solving; Process; Proteins; RNA; Regulation; Research; Resolution; Signal Transduction; Staging; System; Systems Biology; Technology; Testing; Time; Transcript; Transcriptional Regulation; Uncertainty; Variant; Width; Work; Yeast Model System; chemical kinetics; design; functional genomics; mathematical model; mutant; programs; promoter; prototype; simulation; theories; tool; transcription factor

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 which control development is a central problem of functional genomics and systems biology. Although general technology to solve the problem does not yet exist, it can be solved today for the network of genes which control the segmentation system of Drosophila melanogaster. The research plan to accomplish this goal is an integrated program of experimentation and computational modeling, which will be used 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 and wingless in stripes one nucleus in width. This process creates an extremely precise spatial body plan from imprecise maternal cues. Early patterns containing considerable noise and variation between individuals are transformed into highly precise late patterns with little variation. The work proposed will result in a realistic and predictive theory of pattern formation and error correction in the morphogenetic field that determines Drosophila segmentation. The specific aims are to 1) Make use of a chemical kinetic model describing the the evolution of the expression pattern of the segmentation genes during the blastoderm stage to precisely understand how each expression domain of every segmentation gene forms where and when it does. 2) Obtain a new set of quantitative data at both the RNA and protein levels in both wild type and mutants. We will use this new data to 3) Understand and characterize how variation between embryos is canalized into a reliable and size compensated pattern in both wild type and mutants. Accomplishing these aims will require us to 4)Construct a prototype Laboratory Information Management System (LIMS) with new simulation tools connected to an expanded internet database to make all of our data and simulation tools available on the web.

相互作用的基因网络控制着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和系统生物学的中心问题。虽然 通用技术解决的问题还不存在，它可以在今天为基因网络解决 它们控制着果蝇的分割系统。实现这一目标的研究计划 Goal是一个集实验和计算建模于一体的程序，将用于 描述以母体梯度编码的位置信息被转换成 节段性基因嵌合和无翼在一核条纹中的精确稳定表达 宽度。这一过程从不精确的母体线索中创建了一个极其精确的空间身体计划。早些时候 包含相当大的噪声和个体之间差异的图案被转换成高度精确的 花型较晚，变异较小。所提出的工作将产生一个现实的和可预测的模式理论 决定果蝇分割的形态发生域中的形成和纠错。 具体的目标是：1)利用一个化学动力学模型来描述 胚胎期基因片段的表达模式以准确了解每个基因如何 每个片段基因的表达结构域都会在何时何地形成。2)获取一组新的 野生型和突变体在RNA和蛋白质水平上的定量数据。我们将使用这些新数据 3)了解和描述胚胎之间的差异是如何形成可靠的和大小的 野生型和突变型的补偿模式。要实现这些目标，我们需要建立 实验室信息管理原型系统(LIMS)及其与AN的连接 扩展了互联网数据库，使我们所有的数据和模拟工具都可以在网上使用。