Inter-organ signals regulating metabolism, physiology and developmental timing

调节新陈代谢、生理和发育时间的器官间信号

基本信息

批准号：
9273542
负责人：
MICHAEL Brendan O'CONNOR
金额：
$ 37.13万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2021-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Identifying and characterizing physiologic mechanisms that regulate organ communication and function during development and adulthood is vital for understanding how many important human health problems arise and intensify during our lifetimes. This proposal outlines a research strategy to further characterize key signaling systems that regulate critical and likely conserved physiological processes. These include determining how Drosophila TGF-β -type factors control fundamental aspects of muscle, and fat body cellular function and how neuroendocrine mechanisms regulate steroid production, release, and trafficking in response to nutrient availability. We will use a wide variety of modern biological investigative methods including genetic analysis, metabolomics, transcriptome characterization, chromatin immunoprecipitation experiments, biochemistry, and optical/EM imaging to answer these questions. Impact on human health: The successful completion of these aims will provide novel insight into how TGF-β-type factors parse out specific, as well as combinatorial control, over fundamental cellular processes and inter-organ communication programs. It is expected that this knowledge will serve as useful paradigm for understanding the more complex vertebrate system and will afford novel insights into mechanisms that contribute to a number of complex human disorders including obesity, metabolic syndrome, and muscle wasting. In addition, our identification and characterization of new signals that regulate steroid production and trafficking in response to various environmental cues, should provide fresh insights into ways in which nutrition gates puberty in humans.

描述（由申请人提供）：识别和表征发育和成年期间调节器官通讯和功能的生理机制对于了解在我们的一生中有多少重要的人类健康问题出现和加剧至关重要。该提案概述了进一步表征关键信号传导的研究策略。这些系统包括确定果蝇 TGF-β 型因子如何控制肌肉和脂肪体细胞功能的基本方面，以及神经内分泌机制如何调节类固醇的产生、释放和运输。我们将使用多种现代营养物质。生物研究方法包括遗传分析、代谢组学、转录组表征、染色质免疫沉淀实验、生物化学和光学/电磁成像来回答这些问题对人类健康的影响：这些目标的成功完成将为了解 TGF-β 型如何产生新的见解。因子解析出对基本细胞过程和器官间通讯程序的特定和组合控制，预计这些知识将成为理解更复杂的脊椎动物系统的有用范例。对导致肥胖、代谢综合征和肌肉萎缩等多种复杂人类疾病的机制的新见解此外，我们对响应各种环境线索调节类固醇产生和运输的新信号的识别和表征应该提供新的见解。研究营养控制人类青春期的方式。