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Depth and Breadth of Explanatory Power in Developmental GRNs

发展 GRN 解释力的深度和广度

基本信息

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
项目类别：
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

项目摘要

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.

拟议的工作分为三大领域：福尔斯。最初的目标是延长解决基因调控网络（GRNs）控制海胆胚胎规格，原肠胚阶段，包括整个胚胎。这将需要重新解决胚胎的一个剩余的复杂结构域。在此之后，我们将建立一个预测性的数字计算模型，从受精后几个小时到30小时的整个胚胎的监管规范，包括域之间的所有相互作用，使用的方法和软件最近应用于胚胎的内中胚层的一半。第二个目标是利用合成再工程，以确定逻辑处理功能，并回答其他问题的意义，特别是网络子电路设计中遇到的海胆endomesoderm GRN。具体来说，我们将针对双负门电路，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，提出了一组合作建议，其中戴维森实验室将与麦克雷实验室共同努力，其主要目标是破译形态发生功能的控制电路，戴维森实验室将与布朗纳实验室共同努力，以帮助他们的目标，获得比较GRN分析颅神经嵴和躯干神经嵴。