Inter-organ signals regulating metabolism, physiology and developmental timing

 描述（由申请人提供）：识别和表征在发育和成年期间调节器官通信和功能的生理机制对于理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，释放和运输以响应营养物质的可用性。我们将使用各种现代 生物学研究方法，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/EM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TGF-β型因子如何解析出特定的以及组合控制基本细胞过程和器官间通讯程序提供新的见解。预计这些知识将作为理解更复杂的脊椎动物系统的有用范例，并将提供对导致许多复杂人类疾病（包括肥胖、代谢综合征和肌肉萎缩）的机制的新见解。此外，我们对调节类固醇生产和贩运以应对各种环境线索的新信号的识别和表征，应该为营养门人类青春期的方式提供新的见解。

 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.