COMPUTATIONAL MODEL OF GENE REGULATORY PROGRAM

基因调控程序的计算模型

• 批准号: 6387112
• 负责人: ERIC H DAVIDSON
• 金额: $ 27.15万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6387112
• 关键词: computer simulation; confocal scanning microscopy; developmental genetics; early embryonic stage; endoderm; genetic models; genetic regulatory element; invertebrate embryology; mesoderm; model design /development; sea urchins; site directed mutagenesis; transcription factor

DESCRIPTION (adapted from investigator's abstract): It is proposed to construct a computational model which precisely describes the genomic regulatory apparatus required for endomesoderm specification in sea urchin embryos. The model is to be couched in terms of specific, experimentally verifiable or falsifiable predictions that define necessary inputs and outputs of key cis regulatory elements. These are elements which control expression in time and space of genes encoding transcription factors and certain signaling components, which other evidence has identified as relevant genes required in the process of endomesoderm specification. A first stage model of this kind has been built. The investigators will carry out kinetic measurements required to ascertain logical interrelations within the relevant cis regulatory systems and other experiments designed to test architectural features of the computational model. These studies will examine the predicted effects of target site mutations on spatial expression of genes involved in endomesoderm specification, under specific conditions of perturbation. They will also generate a 3D digital construction of the embryo through time, using confocal imaging data, and impose on it the gene expression profiles predicted by the computational regulatory model. The model will ultimately constitute a quantitative computational analysis of a genomic regulatory network, defined at the DNA sequence level, the function of which is to organize a complex, major process in animal development.

描述（根据调查员的摘要改编）：提议构建 精确描述基因组调节的计算模型 海胆胚胎中内胚层规范所需的设备。这 模型应以特定的，实验可验证的或 伪造的预测定义了键CI的必要输入和输出 监管要素。这些是在时间上控制表达的元素，并且 编码转录因子和某些信号成分的基因空间， 哪些证据已确定为此过程中所需的相关基因 内胚层规范。已经建立了这种第一阶段模型。 调查人员将进行确定所需的动力学测量 相关的顺式监管系统中的逻辑相互关系和其他 旨在测试计算模型的体系结构特征的实验。 这些研究将研究目标位点突变对 参与内胚胚层规范的基因的空间表达，在 扰动的特定条件。他们还将产生3D数字 随着时间的推移构建胚胎，使用共聚焦成像数据和 强加于计算预测的基因表达谱图 监管模型。该模型最终将构成定量 基因组调节网络的计算分析，定义在DNA 序列水平，其功能是组织一个复杂的主要过程 在动物发展中。