Resistance and resiliency in a natural host-microbe symbiosis

描述（由申请人提供）：拟议研究的长期目标是了解正常人体微生物群及其有益活动的动态稳定性。为了实现这一目标，需要清楚地了解这些基本微生物群落如何形成，它们如何发挥作用，以及在自然和人工干扰下是什么维持它们。为了帮助发现存在于人体内和人体上的数百或数千种微生物之间复杂相互作用的基本规则，科学家们使用简单的模型系统来提供一个窗口，以了解不同细菌共同发挥作用及其宿主的基本原理。一个这样的模型系统是生物发光海洋细菌和它的鱿鱼宿主之间的光器官共生。这种高度特异性的共生仅由一种细菌组成，但每只动物的共生种群中存在几种不同的菌株。了解这些不同菌株相互作用的规则将为了解不同物种在人体内形成健康、稳定群落的方式提供基础。 拟议研究的具体目标是（i）确定共生种群在宿主生命周期中的自然轨迹，（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，即那些从其他种群中获取资源而不对共生功能做出贡献的成员。这些目标将通过多种方法的组合来实现，包括构建细菌突变体，并通过特定的荧光成像来跟踪它们在宿主中的定植，将具有特定共生伙伴的幼年宿主培养到成年，以及通过计算手段来模拟光器官的种群动态。这项研究的结果将提供给人类微生物组研究人员，他们将能够使用这里发现的规则来更好地专注于他们在组成肠道，口腔，皮肤和身体其他地方微生物群落的复杂人群中保持健康状态的研究。

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.