Morphogen Systems: A Math /Experimental Investigation

Morphogen 系统：数学/实验研究

• 批准号: 6915057
• 负责人: FREDERIC Y.M. WAN
• 金额: $ 39.25万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915057
• 关键词: Drosophilidae; biological signal transduction; biological transport; cell communication molecule; cell component structure /function; developmental genetics; genetic transcription; histogenesis; interdisciplinary collaboration; intermolecular interaction; invertebrate embryology; mathematical model; model design /development; receptor binding; receptor expression; tissue /cell culture

DESCRIPTION (provided by applicant): A major goal of developmental biology is to understand how the precise locations of structures and cell types in the embryo are specified. Much of this tissue patterning is orchestrated by morphogens, diffusible molecules that exert qualitatively different effects on cell fate at different concentrations. In many cases, tissue patterning is consistent with an action of morphogen gradients that instruct cells to adopt different fates as a function of their location in space. Such position-dependent assignment of fates is an essential feature of a patterning system. Here we propose to investigate morphogen signaling and pattern formation through an integrated program of mathematical and experimental approaches. We will go beyond phenomenological modeling and explicitly incorporate specific biological processes-receptor binding and dissociation, endo/exocytosis of receptors, degradation, feedback regulation of morphogen and receptor synthesis, etc.--that are known from experiments to influence morphogen-mediated patterning. Our ultimate goal is to develop quantitative, mechanistic, and experimentally testable theories of the signaling and gene transcription that underlie pattern formation. Quantitative theories of morphogen-mediated patterning that are based on known biological processes will advance our understanding of fundamental developmental biology, and may also lead to applications to other complex biological systems, such as signaling and gene-regulatory networks. The results from these applications may help to understand and address many types of human developmental abnormalities.

描述（由申请人提供）：发展生物学的主要目标是了解如何指定胚胎中结构和细胞类型的精确位置。这种组织模式的大部分是由形态植物策划的，这种分散分子在不同浓度下对细胞命运发挥质量不同的分子。在许多情况下，组织模式与形态学梯度的作用一致，该梯度的作用指示细胞采用不同的命运作为其在太空中的位置的函数。这种依赖命运的位置分配是模式系统的重要特征。在这里，我们建议通过数学和实验方法的综合程序研究形态信号传导和模式形成。我们将超越现象学建模，并明确纳入特定的生物学过程受体的结合和解离，受体的内部/胞吐作用，降解，形态学和受体合成的反馈调节等等。我们的最终目标是开发基于模式形成的信号传导和基因转录的定量，机械和实验测试的理论。 基于已知生物学过程的形态学介导的模式的定量理论将提高我们对基本发育生物学的理解，并可能导致应用于其他复杂的生物系统，例如信号传导和基因调节网络。这些应用的结果可能有助于理解和解决许多类型的人类发育异常。