Signaling and Complexity in Dictyostelium

盘基网柄菌的信号传导和复杂性

• 批准号: 6614060
• 负责人: Edward C COX
• 金额: $ 0.47万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6614060
• 关键词: Dictyostelium; biological signal transduction; cell aggregation; cell cell interaction; cell cycle; cyclic AMP; eukaryote; gene induction /repression; histogenesis; intermolecular interaction; mathematical model; microarray technology; model design /development; robotics

DESCRIPTION (PROVIDED BY APPLICANT):Biological order emerges from interactions between vast numbers of macromolecules at the cellular level, between hundreds of cells at the tissue and whole organism level, and between hundreds to thousands of individuals at the population level. Very little quantitative information is available that allows us to describe these interactions with sufficient realism to predict useful kinds of experiments that would have a decisive impact on our understanding of these very different levels of complexity. This is because the information for a serious analysis of many complex systems is only now becoming available, and because the analytical tools are either lacking or underdeveloped. Understanding is further complicated by the fact that the majority of biological systems are non-linear, and thus the outcome of many interacting systems is most often counterintuitive. Here we propose to study the emergence of form in a simple eukaryotic model organism, the cellular slime mold Dictyostelium. This organism, widely used to study the cytoskeleton, cell signaling, and morphogenesis, forms a distinctive and highly organized multicellular fruiting body which arises from a large population of randomly distributed free living amoebae. It is thus a prototypical example of how a complex dynamical system can arise from an initially random state. Our approach relies on detailed realistic quantitative modeling of chemotactic signaling between free living cells on their way to forming a mature differentiated tissue. This approach is combined with molecular and classical genetic analysis of predictions arising from the model. The goal is a detailed test of published models for the propagation of chemotactic waves and the establishment of oscillators in a field of excitable cells. These experiments will allow a deeper understanding of how waveforms, propagation velocities, and wave amplitude are chosen during early morphogenesis. The results will also have a direct bearing on our understanding of how waves propagate in other excitable systems, such as electrical waves in the beating heart, and Ca2+ waves which organize embryonic axes in many vertebrate eggs.

描述（申请人提供）：生物秩序来自互动 在细胞水平的大量大分子之间，数百之间 在组织和整个生物水平的细胞，数百之间 成千上万的人口处于人口水平。数量很少 可以提供信息，使我们能够描述这些互动 足够的现实主义预测有用的实验 对我们对这些截然不同水平的理解的决定性影响 复杂。这是因为对许多人进行认真分析的信息 复杂的系统直到现在才变得可用，并且由于分析 工具要么缺乏或欠发达。理解是进一步的 大多数生物系统都是非线性的事实，这使得 因此，许多交互系统的结果通常是 违反直觉。 在这里，我们建议在简单的真核模型中研究形式的出现 有机体，细胞粘液霉菌。这个有机体，习惯了 研究细胞骨架，细胞信号传导和形态发生，形成了独特的 和高度有条理的多细胞水果体，是由大的 随机分布的免费活的变形虫的种群。因此，这是一个 复杂的动力系统如何由一个原型示例 最初是随机状态。 我们的方法依赖于趋化性的详细逼真的定量建模 在形成成熟的途中，自由活细胞之间的信号传导 分化的组织。这种方法与分子和经典结合 对模型产生的预测的遗传分析。目标是详细的 趋化波和传播的已发表模型的测试和 在可激发细胞领域中建立振荡器。这些实验 将更深入地了解波形，传播速度和 在早期形态发生过程中选择波幅度。结果也将 直接与我们对海浪如何在其他人传播的理解有关 可兴奋的系统，例如跳动心中的电波，Ca2+ 在许多脊椎动物卵中组织胚胎轴的波。