Depth and Breadth of Explanatory Power in Developmental GRNs

发展 GRN 解释力的深度和广度

• 批准号: 8752112
• 负责人: ERIC H DAVIDSON
• 金额: $ 63.39万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8752112
• 关键词: Apical; Area; Beds; Biological; Cells; Cephalic; Collaborations; Communities; Complex; Computer Simulation; Computer software; Consultations; Data; Destinations; Development; Developmental Gene; Developmental Process; Drug Targeting; Embryo; Endomesoderm; Engineered Gene; Engineering; Feedback; Fertilization; Foundations; Gastrula; Gene Mutation; Genes; Genomics; Hand; Hereditary Disease; Human; Influentials; Intervention; Investigation; Knowledge; Logic; Medical; Medical Research; Methodology; Methods; Metric; Modeling; Morphogenesis; Neural Crest; Organism; Output; Pathway Analysis; Pattern; Process; Publications; Regulator Genes; Research; Role; Sea Urchins; Signal Transduction; Solutions; Staging; Structure; System; Systems Biology; Testing; Textbooks; Time; Toy; Work; base; comparative; design; developmental genetics; digital; egg; falls; gastrulation; member; predictive modeling; single molecule; symposium

The proposed work falls into three general areas. The Initial objective is to extend solved gene regulatory networks (GRNs) controlling sea urchin embryonic specification, up to gastrula stage, to encompass the whole of the embryo. This will require de novo solution for one remaining complex domain of the embryo. Following this we will build a predictive digital computational model of regulatory specification throughout the embryo from a few h after fertilization to 30h, including all interactions between domains, using the approach and software recently applied to the endomesodermal half of the embryo. A second objective is to utilize synthetic re-engineering to ascertain the logic processing functions and to answer other questions about the meaning of particular network subcircuit designs encountered in the sea urchin endomesoderm GRN. Specifically we will target double negative gate circuitry, feedback circuitry, and also redeploy differentiation gene batteries. These studies will be carried out in the context of the developing embryo, rather than in isolated "toy" circuits, and will utilize combinations of recombineered BACs. Thirdly a set of collaborative proposals is presented in which the Davidson lab will work together with the McClay lab on their major objective of deciphering the control circuitry for morphogenetic functions, and the Davidson lab will work together with the Bronner lab to aid in their objective of obtaining comparative GRN analysis between cranial and trunk neural crest.

拟议的工作大致分为三个方面。最初的目标是将控制海胆胚胎规格的已解决基因调控网络(GRN)扩展到原肠胚阶段，以涵盖整个胚胎。这将需要对胚胎剩余的一个复杂结构域进行从头计算。随后，我们将使用最近应用于胚胎内胚层一半的方法和软件，建立一个从受精后几小时到30小时整个胚胎调控规范的预测性数字计算模型，包括所有结构域之间的相互作用。第二个目标是利用 综合再工程，以确定逻辑处理功能，并回答有关海胆内胚层GRN中遇到的特定网络子电路设计的意义的其他问题。 具体地说，我们将瞄准双负极门电路、反馈电路，并重新部署分化基因电池。这些研究将在胚胎发育的背景下进行，而不是在孤立的“玩具”电路中进行，并将利用重组BAC的组合。第三，提出了一套合作建议，其中Davidson实验室将与McClay实验室合作，共同致力于破译形态发生功能的控制电路，Davidson实验室将与Bronner实验室合作，帮助实现他们的目标，即获得脑和躯干神经脊之间的GRN比较分析。