Identifying the Rules Governing Host-Microbiome Composition and Function

确定宿主微生物组成和功能的规则

• 批准号: 10618392
• 负责人: Sara Lindsay Jackrel
• 金额: $ 39.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618392
• 关键词: Bacteria; Bacterial Genes; Biological; Communities; Complex; Consumption; Diet; Disease; Ecology; Engineering; Environment; Eukaryota; Eukaryotic Cell; Evolution; Fingerprint; Flow Cytometry; Gene Expression; Genetic; Goals; Health; Homeostasis; Human; Maintenance; Microbe; Phytoplankton; Process; Recording of previous events; Research; Role; Structure; System; Taxonomy; Testing; Therapeutic; Work; built environment; host microbiome; improved; insight; microbial; microbial community; microbiome; microbiome composition; programs; response; success; theories; trait

Project Summary/Abstract All eukaryotes harbor host-associated microbiomes. Determining what regulates host-microbiome function has the potential to revolutionize our approaches towards maintenance of host health. Host genetics and the environment are two key factors that contribute towards host-microbiome composition and function. We aim to advance our understanding of the relative roles of these two factors in regulating assembly of microbial communities, short-term changes in these communities through ecological succession, and long-term changes through evolutionary processes. Further, microbiomes are complex biological networks. Understanding the underlying structure of ecological interactions within these networks can improve predictions for when and how microbiomes might confer beneficial versus deleterious functions associated with disease. Our lab aims to advance fundamental understanding of host-microbiomes by leveraging the microbiomes of microbes. Specifically we employ single-celled eukaryotic phytoplankton as a highly-tractable experimental system. To further these goals we will focus on the following three themes over the next five years. (1) We will couple the unparalleled diversity of phytoplankton with bacterial –omics approaches to test how microbiomes assemble in response to host genetics. By assessing bacterial gene expression responses to host genetics, in tandem with fluctuating environmental conditions, this work will lend insights in to the host genetic x environmental forces that drive microbiome assembly of eukaryotic microbiomes. (2) We will evaluate mechanisms of microbiome change for maintenance of host homeostasis in fluctuating environments, including ecological shifts in bacterial taxonomic composition, shifts in bacterial gene expression, and bacterial strain evolution. It is important to understand the relative roles of these mechanisms because each occurs over different timescales and their effects can have varying degrees of permanence on their host. (3) We will leverage classical community ecology theory in biological networks with recent advances in flow cytometry bacterial fingerprinting to characterize traits of transient versus stable microbiome networks. We will quantify bacteria-bacteria interaction strengths within naturally assembled and engineered microbiomes to understand how network structure contributes to transitions between host health and disease states. Additionally, our research program will elucidate the implications of declining microbial diversity on eukaryotic host health. We will study host- microbiome co-evolutionary mismatches, such as those caused by humans consuming processed diets and living in human-built environments that differ from those of our evolutionary history. Ultimately, our work will leverage a highly tractable experimental system to advance our understanding of the microbiomes that modulate human health.

项目摘要/摘要 所有真核生物都有宿主相关的微生物群。确定调节宿主微生物组功能的因素有 有可能彻底改变我们维持宿主健康的方法。寄主遗传学与 环境是影响寄主微生物群组成和功能的两个关键因素。我们的目标是 加深对这两个因子在调节微生物组装中的相对作用的理解 群落、通过生态演替在这些群落中的短期变化和长期变化 通过进化过程。此外，微生物群是复杂的生物网络。了解 这些网络中的生态相互作用的底层结构可以改进对时间和方式的预测 微生物群可能赋予与疾病相关的有益功能与有害功能。我们实验室的目标是 通过利用微生物的微生物群落，促进对宿主微生物群落的基本了解。 具体地说，我们使用单细胞真核浮游植物作为一个高度易处理的实验系统。至 在实现这些目标的基础上，今后五年我们将重点抓好以下三个主题。(1)我们将结对 用细菌组学方法测试浮游植物的无与伦比的多样性 对宿主遗传学的反应。通过评估细菌基因表达对宿主遗传学的反应，与 不断变化的环境条件，这项工作将有助于深入了解宿主的遗传x环境作用力 驱动真核微生物群组装的微生物群。(2)我们将评估微生物组的作用机制 在波动的环境中维持寄主动态平衡的变化，包括细菌的生态变化 分类组成，细菌基因表达的转变，以及细菌菌株的进化。重要的是要 了解这些机制的相对作用，因为每种机制都发生在不同的时间尺度上，并且 效果可以在其宿主上具有不同程度的永久性。(3)我们将利用古典社区 生物网络中的生态学理论与流式细胞术细菌指纹图谱的最新进展 描述瞬变与稳定微生物组网络的特征。我们将对细菌进行量化-细菌 自然组装和工程设计的微生物体内的相互作用强度，以了解网络如何 结构有助于宿主健康和疾病状态之间的转换。此外，我们的研究计划 将阐明微生物多样性下降对真核宿主健康的影响。我们将研究主持人- 微生物组共同进化错配，如人类食用加工饲料和 生活在与我们进化史不同的人类建造的环境中。最终，我们的工作将 利用高度易处理的实验系统来促进我们对微生物群的理解 调节人类健康。