Modeling how keystone individuals emerge and influence disease transmission

 描述(申请人提供)：集体行为产生于组成复杂系统的主体的协调行动。人类生活在国家和国家等错综复杂的社会中，组织中的细胞在发育过程中集体协调自己的行动，动物群体执行集体行为，如集群。因此，理解集体行为是如何出现的，对一系列学科都有重要的意义。传统的集体行为研究将群体中的所有个体视为相同的代理人。然而，个体变异在自然界中是普遍存在的，集体几乎总是由表型不同的个体组成。这种异质性导致某些个体对群体的集体表现产生了不成比例的巨大影响。这类个体在生物学中很常见，例如，“超级传播者”促进了流行病在人类社会中的快速传播，“先锋”细胞在发育过程中协调其他细胞的运动，某些个体在人类和非人类灵长类动物群体中监督其他细胞的行为。因此，令人惊讶的是，很少有理论或实证工作来解释基石个人对集体行为的原因和后果。我们的目标是通过对群居蜘蛛Stegodyphus umicola的研究，揭示Keystone个体在塑造集体结果中的作用，特别是疾病动力学，这种蜘蛛非常容易受到实验操作。我们将从揭示Keystone个人如何在有益的集体结果和疾病传播之间进行权衡开始。我们将把经验工作与基于代理人的模拟和常微分方程式结合起来，对集体结果进行成本效益分析。这一分析将揭示当同时考虑多个集体结果时，基石对集体成功的影响如何变化。然后，我们将确定Keystone个体影响其他群体成员的遗传和社会机制。在包括我们在内的许多研究系统中，Keystone个体催化其他群体成员的行为变化。利用基因表达分析和社会网络理论，我们将揭示Keystone个体如何通过社会互动和对基因表达的影响而导致行为变化。特别是，我们将重点关注Keystone个体对负责正常免疫功能的基因表达的变化。我们的最后一个目标是剖析Keystone个体是如何调节疾病动态的。基于模型预测，我们将检查病原体传播动力学是否同时受到第一个感染个体(零号患者)的身份和决定菌落组成的行为规则的影响。当Keystone或普通个体是第一个受感染的个体时，我们将通过跟踪标记细菌在整个群体中的传播来测试这一点。通过结合实验和建模研究机制和功能，我们的工作将填补我们在理解Keystone个人如何影响集体结果方面的经验和理论空白，重点是疾病在整个社会的传播。

 DESCRIPTION (provided by applicant): Collective behavior emerges from the coordinated actions of agents comprising complex systems. Humans live in intricate societies such as states and countries, cells in a tissue collectively coordinate their actions during development, and animal groups perform collective behaviors such as flocking. Thus, understanding how collective behaviors emerge has fundamental implications for a wide range of disciplines. Traditional studies of collective behavior have treated all individuals in a group as identical agents. However, individual variation is prevalent in nature and collectives are almost always comprised of phenotypically heterogeneous individuals. This heterogeneity results in a disproportionately large influence of certain individuals referred to here as 'keystone individuals, over the collective performance of the group. Such keystone individuals are prevalent in biology, for example, 'super-spreaders' facilitate the rapid spread of epidemics in human societies, 'pioneer' cells coordinate the movement of other cells during development, and certain individuals police the behavior of others in human and non-human primate groups. Therefore, it is surprising that there has been only little theoretical or empirical work explaining the causes and consequences of keystone individuals on collective behavior. Our goal is to uncover the role of keystone individuals in shaping collective outcomes, and in particular disease dynamics, by studying the social spider, Stegodyphus dumicola, which is highly amenable to experimental manipulations. We will begin by uncovering how keystone individuals lead to tradeoffs between beneficial collective outcomes and disease transmission. We will combine empirical work with agent-based simulations and ordinary differential equations to produce a cost-benefit analysis of collective outcomes. This analysis will reveal how the effect of keystones on collective success changes when multiple collective outcomes are considered simultaneously. We will then determine the genetic and social mechanisms by which keystone individuals influence other group members. In many study systems, including ours, the keystone individual catalyzes behavioral changes in its fellow group members. Using gene expression analysis and social network theory we will uncover how keystone individuals cause behavioral changes through social interactions and influence on gene expression. In particular, we will focus on the changes caused by keystone individuals to the expression of genes that are responsible for proper immune function. Our last aim is to dissect how disease dynamics are mediated by keystone individuals. Based on model predictions, we will examine if pathogen spread dynamics are influenced by both the identity of the first infected individual (patient zero) and the behavioral rules that determine colony composition. We will test this by tracing the spread of tagged bacteria throughout the colony when a keystone or generic individual are the first infected individual. By investigating mechanisms and function using a combination of experiments and modeling, our work will fill empirical and theoretical gaps in our understanding of how keystone individuals influence collective outcomes focusing on disease spread through a society.