Signaling and Complexity in Dictyostelium

描述(申请人提供)：生物秩序产生于相互作用 在细胞水平上的大量大分子之间，在数百 在组织和整个有机体水平上的细胞，以及数百到 数以千计的个体在人口层面上。数量很少 我们可以使用信息来描述这些交互作用 足够的现实性来预测有用的实验类型，这些实验将具有 对我们理解这些非常不同的水平产生决定性的影响 复杂性。这是因为对于认真分析的信息很多 复杂的系统现在才变得可用，而且因为分析 工具不是缺乏就是不发达。理解是进一步的 大多数生物系统是非线性的，这一事实使情况变得复杂， 因此，许多交互系统的结果通常是 有违常理。 在这里，我们建议在一个简单的真核细胞模型中研究形态的出现 有机体，细胞黏菌Dictyostelial.这种有机体，被广泛用于 研究细胞骨架、细胞信号和形态发生，形成独特的 和高度组织的多细胞子实体，从一个大的 随机分布的自由生活的阿米巴虫种群。因此，它是一种 一个复杂的动力系统如何从一个 最初是随机状态。 我们的方法依赖于详细的、真实的化学趋化性定量模型 在自由活细胞形成成熟细胞的过程中发出信号 分化的组织。这种方法是分子和经典相结合的 对模型所产生的预测进行遗传分析。目标是一个详细的 对已发表的趋化波传播模型和 在可兴奋细胞的场中建立振荡器。这些实验 将使您能够更深入地了解波形、传播速度和 波幅是在早期形态发生过程中选择的。结果也将是 直接关系到我们对波如何在其他介质中传播的理解 兴奋性系统，如心脏跳动中的电波和钙离子 在许多脊椎动物卵中组织胚轴的波。

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.