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类微生物群及其有益活动的动态稳定性。要实现这一目标，需要清楚地了解这些基本微生物群落是如何形成的，它们是如何运作的，以及在面对自然和人为干扰时是什么维持了它们。为了帮助发现存在于人体内外的数百或数千种微生物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及其宿主的基本原理。一个这样的模型系统是生物发光的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，但在每种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中健康、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

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.