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: 10653470
• 负责人: Sara Lindsay Jackrel
• 金额: $ 6.19万
• 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/10653470
• 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; base; built environment; host microbiome; improved; insight; microbial; microbial community; microbiome; microbiome composition; programs; response; theories; trait

Project 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 所有真核生物都有宿主相关的微生物组。确定是什么调节宿主微生物组功能， 有可能彻底改变我们维护宿主健康的方法。宿主遗传学和 环境是影响宿主微生物组组成和功能的两个关键因素。我们的目标是 进一步了解这两个因素在调节微生物组装中的相对作用， 群落，这些群落通过生态演替的短期变化，以及长期变化 通过进化过程。此外，微生物组是复杂的生物网络。了解 这些网络中生态相互作用的基本结构可以改善对何时以及如何进行的预测 微生物组可能赋予与疾病相关的有益功能与有害功能。我们的实验室旨在 通过利用微生物的微生物组来推进对宿主微生物组的基本理解。 具体来说，我们采用单细胞真核浮游植物作为高度易于处理的实验系统。到 为了实现这些目标，我们将在今后五年里重点关注以下三个主题。(1)我们将把 用细菌组学方法测试浮游植物的无与伦比的多样性， 对宿主基因的反应。通过评估细菌基因表达对宿主遗传学的反应， 波动的环境条件，这项工作将有助于深入了解宿主的遗传x环境力量 驱动真核微生物组的微生物组组装。(2)我们将评估微生物组的机制 在波动的环境中维持宿主体内平衡的变化，包括细菌的生态变化， 分类组成、细菌基因表达的变化和细菌菌株进化。重要的是要 理解这些机制的相对作用，因为每个机制都发生在不同的时间尺度上， 对宿主的持久性程度各不相同。(3)我们将利用古典社区 生态学理论在生物网络与最新进展的流式细胞术细菌指纹， 表征瞬时与稳定微生物组网络的特征。我们将量化细菌-细菌 自然组装和工程微生物组内的相互作用强度，以了解网络如何 结构有助于宿主健康状态和疾病状态之间的过渡。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。我们要学习主持人- 微生物组共同进化的不匹配，例如人类食用加工饮食和 生活在人类建造的环境中，这些环境与我们进化史上的环境不同。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组的理解， 调节人类健康。