Signaling and Complexity in Dictyostelium

描述（由申请人提供）：生物秩序从相互作用中产生 在细胞水平上的大量大分子之间， 组织和整个生物体水平的细胞，以及数百至 成千上万的人在人口水平。数量很少 信息是可用的，使我们能够描述这些相互作用， 足够的现实主义来预测有用的实验， 对我们理解这些不同层次的 复杂性这是因为对许多信息进行认真分析 复杂的系统现在才变得可用，因为分析 工具要么缺乏，要么不发达。理解更进一步 由于大多数生物系统都是非线性的， 因此，许多相互作用的系统的结果往往是 违反直觉 在这里，我们建议在一个简单的真核生物模型中研究形式的出现 细胞黏菌Dictyosteophilus。这种有机体广泛用于 研究细胞骨架，细胞信号和形态发生，形成了一个独特的 高度组织化的多细胞子实体， 随机分布的自由生活阿米巴原虫种群。因此， 一个复杂的动力系统如何从一个 初始随机状态。 我们的方法依赖于详细的现实的定量模型的趋化 在自由活细胞形成成熟的 分化组织这种方法结合了分子和经典 从模型中产生的预测的遗传分析。目标是详细的 检验已发表的趋化波传播模型， 在一个可兴奋的细胞场中建立振荡器。这些实验 将允许更深入地了解波形，传播速度， 在早期形态发生期间选择波振幅。结果也将 直接关系到我们对波如何在其他介质中传播的理解。 可兴奋系统，如跳动的心脏中的电波和Ca2+ 在许多脊椎动物卵中组织胚胎轴的波浪。

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.