Doctoral Dissertation Research: Microbial Community Assembly in Primates

博士论文研究：灵长类微生物群落组装

• 批准号: 1455848
• 负责人: Anne Yoder
• 金额: $ 2.96万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-15 至 2017-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1455848&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Microbial; Community

The gut is home to tens of trillions of bacteria that are integral for nutrient digestion, gut development, and defense against disease. But it is not clear how these communities of microbes are established, how they respond to diet and disease, and how they may change through an individual's life. This project will characterize and compare the colonization process from birth to weaning in infants of three lemur species, each with a unique gut morphology and life history. Additional sampling from the weaned infants of one lemur species will track the re-colonization process after infection with Cryptosporidium, an intestinal pathogen. Colonization after birth and disease will be compared to elucidate the rules governing gut community development. Because lemurs and humans are both primates, the study findings may have a profound impact on current understanding of the role of microbiota in human health and development. Additional broader impacts include training of a female graduate student in the STEM sciences, and extensive public science education and outreach efforts. This two-year project will analyze bacterial 16S rDNA and metagenomic profiles to tease apart the potentially divergent effects of host phylogenetic history and diet on the gut microbiota community structure and to examine the associated microbial signatures for potential effects on lemur health and nutritional uptake. Fecal samples will be collected at the Duke Lemur Center from Varecia variegata (frugivorous), Lemur catta (generalist), and Propithecus coquereli (folivorous). DNA will be extracted and sequenced using two different approaches to determine which bacterial species are present and what functions each community can perform. First, the v4 region of the 16S gene will be sequenced and analyzed to identify bacterial taxa and measure their frequencies in each community. Next, the investigators will sequence genomic reads from the entire microbiome, which includes viruses, fungi, protozoans, and other organisms in addition to bacteria. Metagenomic reads will be compared to NCBI databases to identify all (bacterial and non-bacterial) community members, as well as the functions encoded by the genes from each community. This will be the first project to intensively and longitudinally study the composition and community development of gut microbiota across multiple species within a phylogenetically related but ecologically diverse group of mammals, thus enabling modeling of ecological processes in the gut for application to other primates, including humans. A novel bioinformatics pipeline for metagenomic data analysis will be made publicly available as an open source tool through an online repository. The proposed activities will not only shed light on microbial contributions to primate evolution and ecology, but the results will provide a springboard for public education through local outreach.

肠道是数十万亿细菌的家园，这些细菌是营养消化，肠道发育和防御疾病的必要组成部分。但是，尚不清楚如何建立这些微生物社区，它们如何应对饮食和疾病，以及它们如何通过个人的生活改变。该项目将表征并比较从出生到三种狐猴物种的婴儿断奶的殖民过程，每种殖民过程具有独特的肠道形态和生活史。从一个狐猴的肠道病原体感染后，从一个狐猴的weat婴儿中进行的其他取样将跟踪重新殖民化过程。将比较出生和疾病后的殖民化，以阐明有关肠道社区发展的规则。由于狐猴和人类都是灵长类动物，因此研究结果可能对当前对微生物群在人类健康和发展中的作用的理解有深远的影响。其他更广泛的影响包括对STEM科学领域的女研究生的培训以及广泛的公共科学教育和外展工作。这个为期两年的项目将分析细菌16S rDNA和元基因组概况，以嘲笑宿主系统发育史和饮食对肠道微生物群社区结构的潜在不同影响，并检查相关的微生物特征，以实现对狐猴健康和营养摄取的潜在影响。粪便样品将在Varecia Variegata（Froogivovor），Lemur Catta（通才）和Propithecus Coquereli（Folivoroofore）的Duke Lemur Center收集。将使用两种不同的方法提取和测序DNA，以确定存在哪些细菌物种以及每个社区可以执行的功能。首先，将对16S基因的V4区域进行测序和分析，以识别细菌分类单元并测量每个社区中其频率。接下来，研究者将对整个微生物组的基因组读取，其中包括病毒，真菌，原生动物和其他生物体，除了细菌外。将将元基因组读取与NCBI数据库进行比较，以识别所有（细菌和非细菌）社区成员以及每个社区基因所编码的功能。这将是第一个在系统发育相关但在生态上多样化的哺乳动物群体中进行深入和纵向研究肠道菌群对肠道菌群的组成和社区发展的第一个项目，从而实现了肠道中的生态过程的建模，以应用于其他灵长类动物，包括人类，包括人类。通过在线存储库作为开源工具，将公开提供用于宏基因组数据分析的新型生物信息学管道。拟议的活动不仅会阐明微生物对灵长类动物进化和生态学的贡献，而且结果将通过当地的外展为公共教育提供跳板。