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CELLULAR & MOLECULAR STUDIES OF THE DIFFUSE ENDOCRINE SYSTEM

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基本信息

批准号：
9567000
负责人：
Craig A Micchelli
金额：
$ 22.88万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-20 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9567000
关键词：
Address Adipose tissue Affect Animal Model Assimilations Biochemical Biological Biological Models CREB1 gene Cell physiology Cells Communities Complex Cues Cyclic AMP Cyclic AMP-Dependent Protein Kinases Data Diabetes Mellitus Diffuse Disease Dissection Distant Drosophila genus Endocrine Endocrine system Enteral Enteroendocrine Cell Environment Enzymes Epithelial Epithelium Experimental Models Exposure to Fat Body Foundations G-Protein-Coupled Receptors Gastrointestinal tract structure Genetic Models Genetic Transcription Health Homeostasis Hormones Human Link Lipid Mobilization Lipids Lipolysis Mammals Mediating Methods Microbe Microbiology Midgut Modeling Molecular Molecular Genetics Nutrient Nutritional Obesity Organ Organism Pathway interactions Peptidoglycan Peripheral Physiological Physiology Play Process Production Pseudomonas Resolution Signal Pathway Signal Transduction System Tachykinin Testing Tissues United States Work base cytokine gastrointestinal epithelium gene function gut endocrine cell gut microbiota hormonal signals human disease improved in vivo insight microbial microbial community novel novel therapeutics peptide hormone programs remote control repaired response tool

项目摘要

PROJECT SUMMARY/ABSTRACT The Drosophila midgut provides a useful model for understanding the mammalian gastrointestinal tract. Great progress has been made in associating specific configurations of our gut microbial communities with distinct physiological states. Yet, precisely how enteroendocrine cells embedded in the gut epithelium signal peripheral tissues in response to these dynamically changing microbial cues is less well understood. Our preliminary studies have laid the foundation for a powerful new Drosophila model of the enteroendocrine system. These observations raise the central hypothesis that endocrine cells signal over a long-range to control homeostasis of distant tissues. We propose to characterize the mechanism(s) by which enteroendocrine cells signal peripheral tissues. These questions are currently difficult to address in mammals, as the tools for conditionally manipulating both endocrine cell subtypes and peripheral target tissues with single cell resolution have not yet been established. Thus, we propose to use Drosophila as a model to dissect mechanisms controlling the endocrine system.

项目总结/摘要果蝇中肠为了解哺乳动物胃肠道提供了一个有用的模型。在将我们肠道微生物群落的特定配置与不同的生理状态相关联方面取得了很大进展。然而，确切地说，嵌入肠道上皮的肠内分泌细胞是如何响应这些动态变化的微生物线索而向外周组织发出信号的，还不太清楚。我们的初步研究奠定了基础，一个强大的新的果蝇模型的肠内分泌系统。这些观察结果提出了一个中心假设，即内分泌细胞发出长距离信号，以控制远处组织的稳态。我们提出了肠内分泌细胞信号的外周组织的机制的特点。这些问题目前在哺乳动物中难以解决，因为用于以单细胞分辨率有条件地操纵内分泌细胞亚型和外周靶组织的工具尚未建立。因此，我们建议使用果蝇作为一个模型来解剖控制内分泌系统的机制。