Inter-organ signals regulating metabolism, physiology and developmental timing

 描述(由申请人提供)：识别和描述在发育和成年期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。这项建议概述了一种研究策略，以进一步表征调节关键和可能保守的生理过程的关键信号系统。这些包括确定果蝇转化生长因子-β类因子如何控制肌肉和脂肪身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，以响应营养的可获得性。我们将使用各种各样的现代 生物学研究方法包括遗传分析、代谢组学、转录组鉴定、染色质免疫沉淀实验、生物化学和光学/EM成像。对人类健康的影响：这些目标的成功实现将为转化生长因子-β类型的因子如何解析出对基本细胞过程和器官间通讯程序的具体和组合控制提供新的见解。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，并将为导致包括肥胖、代谢综合征和肌肉萎缩在内的许多复杂人类疾病的机制提供新的见解。此外，我们识别和表征了调节类固醇生产和贩运的新信号，以响应各种环境线索，应该为研究营养对人类青春期的影响提供新的见解。

 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.