Resistance and resiliency in a natural host-microbe symbiosis

描述（由申请人提供）：所提议研究的长期目标是了解正常人类微生物群的动态稳定性及其有益活性。为了实现这一目标，需要清楚地了解这些重要的微生物群落是如何形成的、它们是如何发挥作用的，以及在自然和人为扰动面前是什么维持它们的。为了帮助发现人体内外数百或数千种微生物物种之间复杂相互作用的规则，科学家们使用简单的模型系统来提供了解不同细菌共同发挥作用以及与宿主相互作用的基本原理的窗口。其中一个模型系统是生物发光海洋细菌与其鱿鱼宿主之间的光器官共生。 This highly specific symbiosis consists of only one bacterial species, but there are several distinct strains present in the symbiotic population in each animal.了解这些不同菌株相互作用的规则将为了解不同物种如何在人体内形成健康、稳定的群落奠定基础。 拟议研究的具体目标是（i）确定共生种群在宿主生命中的自然轨迹，（ii）确定种群抵抗其他细菌入侵的方式，以及（ii）确定 共生体如何保护自己免受“骗子”的侵害，这些“骗子”成员从其他群体中获取资源而不为共生功能做出贡献。这些目标将通过多种方法来实现，包括构建细菌突变体并通过特定荧光成像追踪其在宿主中的定殖，将具有特定共生伙伴的幼年宿主培养至成年，以及通过计算手段对光器官的种群动态进行建模。这项研究的结果将提供给人类微生物组研究人员，他们将能够利用这里发现的规则更好地集中研究，维持肠道、口腔、皮肤和身体其他部位微生物群落的复杂群体的健康状态。

DESCRIPTION (provided by applicant): The long-term objectives of the proposed research are to understand the dynamic stability characterizing the normal human microbiota and its beneficial activities. To achieve this goal requires a clear understanding of how these essential microbial communities form, how they function, and what maintains them in the face of natural and artificial perturbations. To help discover the rules underlying the complex interactions between the hundreds or thousands of microbial species present in and on the human body, scientists use simple model systems to provide a window into the fundamental principles by which different bacteria function together and with their host. One such model system is the light-organ symbiosis between a bioluminescent marine bacterium and its squid host. This highly specific symbiosis consists of only one bacterial species, but there are several distinct strains present in the symbiotic population in each animal. Understanding the rules by which these different strains interact will provide a foundation for understanding the way different species for healthy, stable communities in the human body. The specific aims of the proposed research are to (i) determine the natural trajectory the symbiotic population over the life of the host, (ii) determine the ways the population resists invasion by other bacteria, and (ii) determine how the symbiosis protects itself against 'cheaters', members that take resources from the rest of the population without contributing to symbiotic functions. These aims will be achieved by a combination of approaches including construction of bacterial mutants and following their colonization of the host by specific fluorescence imaging, raising juvenile hosts with specific symbiotic partners into adulthood, and modeling the population dynamics of the light organs by computational means. The results of this study will be made available to human microbiome researchers, who will be able to use the rules discovered here to better focus their studies of maintaining a healthy state in the complex sets of populations making up the microbial communities in the gut tract, the oral cavity, the skin and elsewhere on the body.