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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/9273542
• 关键词: Adult; Aging; Biochemistry; Biological; Cell physiology; Communication; Communication Programs; Complex; Cues; Development; Disease; Drosophila genus; Fat Body; Health; Homeostasis; Human; Image; Knowledge; Malignant Neoplasms; Metabolic syndrome; Metabolism; Methods; Modernization; Muscle; Muscular Atrophy; Neurosecretory Systems; Nutrient; Obesity; Optics; Organ; Organism; Physiological; Physiological Processes; Physiology; Production; Puberty; Research; Signal Transduction; Steroids; System; Transforming Growth Factor beta; chromatin immunoprecipitation; combinatorial; experimental study; genetic analysis; insight; metabolomics; novel; nutrition; public health relevance; response; trafficking; transcriptome

 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（由适用提供）：识别和表征调节器官沟通和功能在发展和成年期间的生理机制对于了解我们一生中出现和加剧的重要人类健康问题至关重要。该建议概述了一种研究策略，以进一步表征关键和可能构成生理过程的关键信号系统。其中包括确定果蝇TGF -β型因子如何控制肌肉的基本方面，脂肪体细胞功能以及神经内分泌机制如何调节类固醇的产生，释放和运输，以响应营养的可用性。我们将使用各种现代 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/EM成像，以回答这些问题。对人类健康的影响：这些目标的成功完成将为TGF-β型因素如何解析特定和组合控制，对基本的细胞过程和组织间的通信程序，提供新的见解。可以预期，这些知识将是理解更复杂的脊椎动物系统的有用范式，并将对机制提供新的见解，这些机制有助于许多复杂的人类疾病，包括目标，代谢综合征和肌肉浪费。此外，我们对调节类固醇生产和贩运各种环境线索的新信号的识别和表征应提供新的见解，以了解营养门在人类中的青春期的方式。