Inter-organ signals regulating body size, physiology anddevelopmental timing

调节身体大小、生理和发育时间的器官间信号

• 批准号: 10414890
• 负责人: MICHAEL Brendan O'CONNOR
• 金额: $ 38.05万
• 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 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10414890
• 关键词: Activins; Adult; Aging; Animals; Biochemistry; Biological; Body Size; Brain; Cell physiology; Communication; Complex; Cues; Development; Disease; Drosophila genus; Endocrine; Ensure; Health; Homeostasis; Human; Image; Knowledge; Metabolic syndrome; Methods; Modernization; Molecular; Muscle; Muscular Atrophy; Neurosecretory Systems; Obesity; Optics; Organ; Organism; Physiological; Physiological Processes; Physiology; Production; Research; Signal Transduction; Steroids; System; Time; Tissues; Transforming Growth Factor beta; chromatin immunoprecipitation; combinatorial; developmental disease; experimental study; genetic analysis; insight; member; metabolomics; neuronal circuitry; novel; nutrition; response; transcriptome

Inter-organ signals that regulate body size, physiology and developmental timing 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 conserved physiological processes. These include determining how a signaling network of three Drosophila Activin-like members of the TGF-beta superfamily coordinately control fundamental aspects of brain, muscle, and fatbody cellular function in response to environmental variables such as nutrition during development to maintain physiologic homeostasis and how neuroendocrine mechanisms regulate steroid production and release, also in response to various internal and external cues, to properly time developmental maturation. We will use a wide variety of modern biological investigative methods including genetic analysis, neuronal circuit and activity mapping, biochemistry, optical/EM imaging, metabolomics, temporal and tissue specific transcriptome characterization as well as chromatin immunoprecipitation experiments, to answer these questions. Impact on human health: The successful completion of these aims will provide novel insight into how an two very conserved inter-organ signaling networks parse out specific, as well as combinatorial control, over various fundamental cellular processes to produce a properly proportioned animal, that is optimized for survival in its particular ecological niche. It is expected that this knowledge will provide useful paradigms for understanding functional aspects of the more complex, but highly related vertebrate TGF-beta and neuroendocrine signaling systems, and will afford novel insights into molecular mechanisms that contribute to a number of human disorders including obesity, metabolic syndrome, muscle wasting, pubertal disorders and ageing.

管间信号，该信号调节体型，生理和发育时机 识别和表征调节器官的生理机制 发展和成年期间的沟通和功能对于理解至关重要 在我们的一生中，有多少重要的人类健康问题出现和加剧。 该建议概述了一种研究策略，以进一步表征关键信号系统 调节关键和保守的生理过程。这些包括确定 TGF-beta的三个果蝇激活素样成员的信号网络如何 超家族协调控制大脑，肌肉和胖子的基本方面 响应环境变量（例如营养）的蜂窝功能 维持生理稳态以及神经内分泌机制的发展 调节类固醇的产生和释放，也响应各种内部和外部 提示，以适当时间发展成熟。我们将使用各种现代 生物研究方法，包括遗传分析，神经元和活性 映射，生物化学，光学/EM成像，代谢组学，时间和组织特异性 转录组表征以及染色质免疫沉淀实验， 回答这些问题。对人类健康的影响：成功完成这些 目的将提供有关两个非常保守的器官信号传导的新见解 网络对各种基本的特定和组合控制解析和组合控制 蜂窝过程以生产适当的比例动物，该动物已优化 在其特定的生态利基市场中的生存。预计这些知识将提供 有用的范例，用于理解更复杂但高度的功能方面 相关的脊椎动物TGF-β和神经内分泌信号系统，将负担新颖 对有助于多种人类疾病的分子机制的见解 包括肥胖，代谢综合征，肌肉浪费，青春期疾病和衰老。