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：控制人胰腺的microRNA调节模块的发现胰岛功能该研究项目的目的是全面表征人胰岛功能中的microRNA（miRNA）。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，一种以高血糖为特征的慢性疾病，这可能导致重大发病率，包括肾衰竭。基因调节驱动胰岛生物学的网络（GRN）在很大程度上没有表征。 mirnas是转录调节器和GRN的关键组成部分。最近的研究在胰岛功能中暗示miRNA。 miRNA表达和主要人类小岛的活动将大大增加我们对GRN的了解这是胰岛生物学的基础。因此，该项目将使用高通量基因组系统地表征所有miRNA的方法主要人类胰岛（AIM 1），并确定影响其影响其的监管模块差异表达模式（AIM 2）和靶向活动（AIM 3）。这些目标会为映射胰岛贡献很大，这将有助于识别用于解决胰岛病理生理学的临床相关药理学靶标糖尿病。