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（改编自研究者的摘要）：建议构建 精确描述基因组调控的计算模型 海胆胚胎内中胚层规范所需的仪器。这 模型应以具体的、可实验验证的或 定义关键 CIS 必要输入和输出的可证伪预测 监管要素。这些是控制时间和表达的元素 编码转录因子和某些信号成分的基因空间， 哪些其他证据已确定为该过程所需的相关基因 内中胚层规格。这种类型的第一阶段模型已经建立。 研究人员将进行必要的动力学测量以确定 相关独联体监管体系和其他体系内的逻辑相互关系 旨在测试计算模型的架构特征的实验。 这些研究将检验靶位点突变对的预测影响 参与内中胚层规范的基因的空间表达，在 扰动的具体条件。他们还将生成 3D 数字 使用共焦成像数据随时间构建胚胎，以及 将计算预测的基因表达谱强加于其上 监管模式。该模型最终将构成一个定量的 DNA 定义的基因组调控网络的计算分析 序列级，其作用是组织一个复杂的、主要的流程 在动物发育中。