Morphogen Systems: A Math /Experimental Investigation

Morphogen 系统：数学/实验研究

• 批准号: 6760156
• 负责人: FREDERIC Y.M. WAN
• 金额: $ 39.17万
• 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/6760156
• 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(申请人提供)：发育生物学的一个主要目标是了解胚胎中结构和细胞类型的准确位置是如何被指定的。这种组织模式很大程度上是由形态因子协调的，形态因子是一种可扩散的分子，在不同的浓度下对细胞命运产生不同的影响。在许多情况下，组织图案化与形态梯度的作用是一致的，形态梯度指示细胞根据其在空间中的位置而采用不同的命运。这种与位置相关的命运分配是图案化系统的基本特征。在这里，我们建议通过数学和实验方法的综合方案来研究形态发生信号和模式的形成。我们将超越现象学建模，明确纳入特定的生物过程-受体结合和解离、受体的内吞/胞吐、降解、形成剂的反馈调节和受体合成等--这些过程是从实验中已知的影响形成剂介导的模式的。我们的最终目标是发展定量的、机械的和可实验测试的信号和基因转录理论，这些理论是模式形成的基础。 基于已知生物过程的形态调控模式的定量理论将促进我们对基础发育生物学的理解，也可能导致将其应用于其他复杂的生物系统，如信号和基因调控网络。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。