Physiological Model of Gene Regulation in Drosophila

果蝇基因调控的生理模型

基本信息

批准号：
7783478
负责人：
John B. Reinitz
金额：
$ 59.55万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-09-30 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7783478
关键词：
Bacteria Basic Science Behavior Biological Process Biology Blastoderm Cell Death Cell Nucleus Cell division Cells Code Communities Computer Simulation Congenital Abnormality Cues DNA Sequence Data Data Set Databases Development Drosophila genus Drosophila melanogaster Embryo Embryonic Development Face Family Gene Expression Gene Expression Regulation Genes Genetic Goals Image Individual Internet Investigation Life Malignant Neoplasms Mathematics Measurement Mechanics Medicine Microarray Analysis Modeling Molecular Natural regeneration Nature Noise Organism Pattern Pattern Formation Physics Physiological Positioning Attribute Problem Solving Process Property Reporter Research Resources Scientist Services Signal Transduction Stress System Systems Biology Technology Testing Translational Research Variant Width Work Wound Healing Yeasts chemical kinetics data modeling functional genomics in vivo infancy mutant new technology preconditioning programs promoter public health relevance theories tissue fixing tool transcription factor

项目摘要

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 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. Our specific aims are to 1) Make use of a family of chemical kinetic models to understand the typical expression and the dynamics of the segmentation genes in wild type and mutants up the initiation of wg and en expression. 2) Exploit these models to gain deeper understanding of robustness, both in a natural context and under stress 3) Perform quantitative live imaging studies of zygotic segmentation genes, supplemented by fixed tissue data from mutants. 4.) Develop new tools to support Aims 1-3 and make them, together with all data, models, and code available to the scientific community through the FlyEx database PUBLIC HEALTH RELEVANCE: This project concerns basic science with long term implications for translational science and medicine. It is concerned with the genetics of development, the scientific understanding of which is a precondition for understanding cancer and birth defects. The project also aims at a precise understanding of canalization in development, an "error correction" process that is closely related to wound healing and regeneration.

描述（由申请人提供）：相互作用的基因网络控制着多种基本的生物过程，包括胚胎发育、细胞分裂和细胞死亡。了解控制发育的整个基因网络的功能是功能基因组学和系统生物学的中心问题。尽管解决该问题的通用技术尚不存在，但今天可以通过控制果蝇分割系统的基因网络来解决。实现这一目标的研究计划是一个实验和计算建模的综合计划，该计划将用于表征母体梯度中编码的位置信息转化为条纹中被卷入和无翅的节段极性基因的精确和稳定表达的过程。宽度为一个核。这个过程根据不精确的母体线索创建了极其精确的空间身体计划。包含相当大的噪音和个体之间差异的早期模式被转化为几乎没有变化的高度精确的晚期模式。所提出的工作将产生确定果蝇分割的形态发生领域中的模式形成和误差校正的现实和预测理论。我们的具体目标是 1) 利用一系列化学动力学模型来了解野生型和突变体中分段基因的典型表达和动态，直至 wg 和 en 表达的起始。 2) 利用这些模型来更深入地了解自然环境和压力下的稳健性 3) 对合子分割基因进行定量实时成像研究，并辅以来自突变体的固定组织数据。 4.) 开发新工具来支持目标 1-3，并通过 FlyEx 数据库将它们与所有数据、模型和代码一起提供给科学界公共卫生相关性：该项目涉及对转化科学和医学具有长期影响的基础科学。它涉及发育遗传学，对其的科学理解是了解癌症和出生缺陷的先决条件。该项目还旨在准确理解发育中的管道化，这是一个与伤口愈合和再生密切相关的“纠错”过程。