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Discovery of microRNA regulatory modules controlling human pancreatic islet funct

发现控制人胰岛功能的 microRNA 调节模块

基本信息

批准号：
8475587
负责人：
Praveen Sethupathy
金额：
$ 23.98万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8475587
关键词：
Address Algorithms Binding Binding Sites Bioinformatics Biological Biological Assay Biology Blood Glucose Cholesterol Chromatin Chronic Collaborations Complex Computer Simulation Computing Methodologies Data Data Analyses Deoxyribonucleases Diabetes Mellitus Elements Epidemic Etiology Foundations Functional disorder Gene Components Gene Expression Profile Gene Targeting Genetic Genetic Transcription Genomics Glucose Goals Growth Hormones Human Hyperglycemia Impairment In Vitro Individual Insulin Insulin Resistance Investigation Islet Cell Islets of Langerhans Kidney Failure Knowledge Lead Maps Mediating Messenger RNA Metabolic Metabolic Diseases MicroRNAs Molecular Morbidity - disease rate Morphology Mus Non-Insulin-Dependent Diabetes Mellitus Obesity Pathogenesis Pathologic Processes Pattern Physiological Physiological Processes Post-Transcriptional Regulation RNA-Induced Silencing Complex Regulation Regulator Genes Regulatory Element Reporting Research Personnel Research Project Grants Rest Role Sequence Analysis Signaling Pathway Gene Site Small RNA Statistical Methods Therapeutic Transcriptional Regulation Universities Zebrafish base blood glucose regulation clinically relevant crosslink epigenomics glucose metabolism human tissue innovation insight insulin secretion islet lipid metabolism mortality novel pancreatic islet function promoter response transcriptome sequencing

项目摘要

Title: Discovery of microRNA regulatory modules controlling human pancreatic islet function The goal of this research project is to characterize comprehensively the role of microRNAs (miRNAs) in human pancreatic islet function. Islet cells are responsible for the metabolic response to changes in blood glucose levels. Progressive dysfunction of the islet underlies type 2 diabetes, a chronic condition characterized by hyperglycemia, which can lead to substantial morbidity including kidney failure. The gene regulatory networks (GRNs) that drive islet biology are largely uncharacterized. miRNAs are post- transcriptional regulators and critical components of GRNs. Recent studies have implicated miRNAs in islet function. Comprehensive analysis of miRNA expression and activity in primary human islets will significantly increase our knowledge of the GRNs that underlie islet biology. Therefore, this project will use high-throughput genomic approaches to systematically characterize all miRNAs in resting and glucose-stimulated primary human islets (Aim 1), and identify the regulatory modules that influence their differential expression patterns (Aim 2) and targeting activity (Aim 3). These aims will contribute significantly toward mapping islet GRNs, which will facilitate the identification of clinically relevant pharmacological targets for addressing islet pathophysiology in diabetes.

标题：发现控制人类胰腺癌的microRNA调控模块胰岛功能本研究项目的目标是全面描述 microRNAs（miRNAs）在人类胰岛功能中的作用。胰岛细胞负责对血糖水平变化的代谢反应。进行性功能障碍胰岛是2型糖尿病的基础，2型糖尿病是一种以高血糖为特征的慢性疾病，这可导致包括肾衰竭在内的严重发病率。基因调控驱动胰岛生物学的GRN网络在很大程度上没有特征。miRNAs是后转录调节因子和GRNs的关键组成部分。最近的研究与胰岛功能相关的miRNA。miRNA表达的综合分析和原代人类胰岛中的活动将显着增加我们对GRN的了解是胰岛生物学的基础因此，本项目将使用高通量基因组系统表征静息和葡萄糖刺激下所有miRNA的方法原代人胰岛（目标1），并确定影响其功能的调控模块。差异表达模式（Aim 2）和靶向活性（Aim 3）。这些目标将显著有助于绘制胰岛GRN，这将有助于识别临床相关的药理学靶点，用于解决胰岛病理生理学，糖尿病