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CONSTRUCTING A HIGH-RESOLUTION GENE REGULATORY NETWORK OF EMT

构建EMT高分辨率基因调控网络

基本信息

批准号：
10203174
负责人：
Jacob F Warner
金额：
$ 41.59万
依托单位：
UNIVERSITY OF NORTH CAROLINA WILMINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10203174
关键词：
ATAC-seq Automobile Driving Bacterial Artificial Chromosomes Binding Sites Bioinformatics Biological Assay Biological Models Candidate Disease Gene Cell physiology Cells Chromatin Complex Data Defect Developmental Process Embryo Embryonic Development Epithelial Event Genes Genetic Transcription Germ Layers Goals Image Invaded Knowledge Link Maps Measures Mentors Mesenchymal Methods Modeling Modernization Molecular Molecular Biology Techniques Morphogenesis Movement Nature Neural Crest Organism Pathway Analysis Positioning Attribute Public Health Publishing Regulator Genes Regulatory Element Reporter Research Personnel Research Project Grants Resolution Rest Role Scanning Science Sea Urchins Students System Techniques Technology Testing Time Time Series Analysis Tissues Training Transitional Epithelium Work cancer cell career epithelial to mesenchymal transition experimental study gastrulation gene complementation gene function knock-down knowledge base mRNA sequencing migration multiple omics myogenesis network models novel programs transcription factor transcriptomics undergraduate student

项目摘要

PROJECT SUMMARY/ ABSTRACT An Epithelial to mesenchymal transition (EMT) is an essential program in many developmental processes including gastrulation, neural crest formation, and myogenesis. EMT is a complex morphogenetic event and, as such, is governed by groups of genes functioning as a gene regulatory network (GRN). Through recent advances in many species we have begun to understand the gene regulatory networks that regulate EMT. However, we still lack information about how these networks function in detail. This is due in part to the slow nature of GRN construction in which a major bottleneck is the identification of cis-regulatory elements. We propose to overcome these limitations and apply novel high throughput methods to construct the first high-resolution gene regulatory network of EMT. The sea urchin embryo represents a unique opportunity to derive such a gene regulatory network of EMT. The EMT of mesenchymal cells in the early sea urchin embryo is predictable, synchronous, and occurs in a transparent embryo. Furthermore, gene regulatory networks describing germ layer specification have been well established in the sea urchin. We propose to build on this knowledgebase and apply new methods in high-throughput network construction to derive a high-resolution gene regulatory network of EMT. This goal will be pursued as two specific aims. In the first aim, we evaluate novel nodes that have been identified using co-expression network analysis. The second aim seeks to use high throughput identification of cis-regulatory elements to identify the EMT network wiring. These aims capitalize on the advanced state of knowledge of EMT and embryonic gene regulatory networks of sea urchin.

项目总结/摘要上皮细胞向间质细胞转化（EMT）是许多发育过程中的重要程序。包括原肠胚形成、神经嵴形成和肌生成的过程。急救队是一个形态发生事件，因此，是由基因组作为一个基因发挥作用，监管网络（GRN）。通过最近在许多物种上的进展，我们已经开始了解调控EMT的基因调控网络。然而，我们仍然缺乏信息，这些网络是如何运作的这部分是由于GRN的缓慢性质构建，其中主要瓶颈是鉴定顺式调节元件。我们我建议克服这些限制，并应用新的高通量方法，构建首个高分辨率的EMT基因调控网络。海胆胚胎代表了一个独特的机会，以获得这样的基因调控网络的EMT。EMT的早期海胆胚胎中的间充质细胞是可预测的，同步的，并且发生在透明胚此外，描述胚层特化的基因调控网络已经在海胆中得到了很好的证实。我们建议在这一知识基础上，在高通量网络构建中应用新方法以获得高分辨率基因 EMT监管网络。这一目标将作为两个具体目标来实现。第一个目标，我们评估已经使用共表达网络分析识别的新节点。的第二个目的是利用顺式调节元件的高通量鉴定来鉴定急救队的网络线路。这些目标利用了先进的EMT知识，海胆的胚胎基因调控网络。