Modeling how keystone individuals emerge and influence disease transmission

模拟关键个体如何出现并影响疾病传播

• 批准号: 9321471
• 负责人: Noa Michal Pinter-Wollman
• 金额: $ 40.15万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321471
• 关键词: Animals; Bacteria; Behavior; Behavioral; Biology; Cells; Complex; Cost-Benefit Analysis; Country; Development; Developmental Disabilities; Differential Equation; Discipline; Disease; Epidemic; Epidemiology; Ethics; Formulation; Gene Expression; Gene Expression Profiling; Generic Drugs; Genes; Genetic; Goals; Health; Heterogeneity; Human; Image Analysis; Immune response; Individual; Infection; Influentials; Lead; Malignant Neoplasms; Mathematics; Mediating; Microbe; Modeling; Molecular; Movement; Nature; Organism; Outcome; Performance; Personality; Phenotype; Plasmids; Play; Police; Public Health; Role; Science; Shapes; Social Interaction; Social Network; Societies; Spiders; Structure; System; Testing; Theoretical model; Tissues; Variant; Work; base; behavioral study; cell behavior; disease transmission; experimental study; immune function; indexing; individual patient; insight; member; nonhuman primate; novel; pathogen; public health relevance; simulation; social; success; theories; transmission process

 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.

 描述（由申请人提供）：集体行为是由复杂系统组成的代理的协调行动产生的。人类生活在错综复杂的社会中，例如州和国家，组织中的细胞在发育过程中集体协调其行为，动物群体则执行诸如聚集等集体行为。因此，理解集体行为如何出现对于广泛的学科具有根本性的影响。传统的集体行为研究将群体中的所有个体视为相同的主体。然而，个体变异在自然界中普遍存在，集体几乎总是由表型异质的个体组成。这种异质性导致某些个体（这里被称为“基石个体”）对群体的集体表现产生不成比例的巨大影响。这种关键个体在生物学中很普遍，例如，“超级传播者”促进了人类社会中流行病的快速传播，“先锋”细胞在发育过程中协调其他细胞的运动，以及某些个体在人类和非人类灵长类动物群体中监管其他细胞的行为。因此，令人惊讶的是，几乎没有理论或实证工作来解释关键个体对集体行为的原因和后果。我们的目标是通过研究非常适合实验操作的社交蜘蛛Stegodyphus dumicola，揭示关键个体在塑造集体结果中的作用，特别是疾病动态。我们将首先揭示关键个体如何在有益的集体结果和疾病传播之间进行权衡。我们将把实证工作与基于主体的模拟和常微分方程相结合，对集体结果进行成本效益分析。该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，我们将确定关键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，关键个体会促进其他群体成员的行为变化。利用基因表达分析和社交网络理论，我们将揭示关键个体如何通过社交互动和对基因表达的影响来引起行为变化。我们将特别关注关键个体对负责正常免疫功能的基因表达造成的变化。我们的最后一个目标是剖析关键个体如何介导疾病动态。根据模型预测，我们将检查病原体传播动态是否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。当一个基石或一般个体是第一个被感染的个体时，我们将通过追踪标记细菌在整个菌落中的传播来测试这一点。通过结合实验和建模来研究机制和功能，我们的工作将填补我们对关键个人如何影响关注疾病在社会中传播的集体结果的理解的经验和理论空白。