Resistance and resiliency in a natural host-microbe symbiosis

描述(申请人提供)：拟议研究的长期目标是了解正常的人类微生物区系及其有益活动的动态稳定性特征。为了实现这一目标，需要清楚地了解这些基本微生物群落是如何形成的，它们是如何发挥作用的，以及在面对自然和人为干扰时是什么维持着它们。为了帮助发现人体内和体内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一个窗口，了解不同细菌共同作用和与宿主一起发挥作用的基本原理。一个这样的模型系统是发光海洋细菌和它的鱿鱼宿主之间的光器官共生。这种高度特异的共生只由一种细菌物种组成，但在每种动物的共生种群中都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理解不同物种在人体内健康、稳定的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一生中的自然轨迹，(Ii)确定种群抵抗其他细菌入侵的方式，以及(Ii)确定 共生关系如何保护自己不受“作弊者”的侵害，“作弊者”是指从其他种群中获取资源，而不是对共生功能做出贡献的成员。这些目标将通过一系列方法来实现，包括构建细菌突变体并通过特定的荧光成像对宿主进行定植，将具有特定共生伙伴的幼年宿主培养成成年期，以及通过计算手段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，他们将能够利用这里发现的规则，更好地专注于在组成肠道、口腔、皮肤和身体其他部位的微生物群落的复杂种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.