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: 10458046
• 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/10458046
• 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 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.

项目概要/摘要 所有真核生物都含有与宿主相关的微生物组，确定调节宿主微生物组功能的因素具有重要意义。 彻底改变我们维持宿主健康的方法的潜力。 环境是影响宿主微生物组组成和功能的两个关键因素。 我们对这两个因素在调节微生物组装中相对先进作用的理解 群落、这些群落通过生态演替而发生的短期变化以及长期变化 此外，微生物组是复杂的生物网络。 这些网络内生态相互作用的基本结构可以改善对何时以及如何相互作用的预测 微生物组可能赋予与疾病相关的有益功能和有害功能。 通过利用微生物的微生物组对宿主微生物组进行基本了解。 我们采用单细胞真核浮游植物作为特别易于处理的实验系统。 为了进一步实现这些目标，我们将在未来五年重点关注以下三个主题（1）我们将结合以下三个主题。 利用细菌组学方法来测试浮游植物无与伦比的多样性，以测试微生物组如何组装 通过评估细菌基因表达对宿主遗传学的反应，同时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遗传x环境力量 (2)我们将评估微生物组的机制。 在波动的环境中维持宿主稳态的变化，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的进化非常重要。 了解这些机制的相对作用，因为每种机制发生在不同的时间尺度及其 （3）我们将利用经典社区 生物网络中的生态理论与流式细胞术细菌指纹识别的最新进展 表征瞬时微生物组网络与稳定微生物组网络的特征我们将量化细菌-细菌网络。 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 此外，我们的研究计划有助于宿主健康和疾病状态之间的转变。 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宿主。 微生物组协同进化不匹配，例如由人类食用加工饮食和 最终，我们的工作将生活在与我们的进化历史不同的人造环境中。 利用高度易于处理的实验系统来增进我们对微生物组的理解 调节人体健康。