CAREER: Molecular functional diversity of microbes and microbiomes

职业：微生物和微生物组的分子功能多样性

• 批准号: 1553289
• 负责人: Yana Bromberg
• 金额: $ 109.12万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1553289&HistoricalAwards=false
• 关键词: CAREER; Molecular; functional; diversity; microbes

Microbes dominate life on Earth. Microbes evolve under the pressure of environmental stresses, such as climate change and pollution; these changes have global impact. For both microbes and their communities (or microbiomes), understanding the consequences of large-scale changes on microbes requires that we understand their starting point under normal conditions. In this project, normal baselines will be defined showing the functional abilities of microbes in a community and environment. Microbes will be grouped into similar functional classes, the 'distance' between two classes will include all of the differences in their functional abilities, which indicates their lifestyle preferences under existing conditions. In this way, a microbial class becomes a small set of shared functions, and is the basis for a novel way to infer microbial and microbiome diversity. The shared functions will serve as a guide to discovering new functional pathways or new members of known pathways, which can lead to broader impacts in a number of industrial applications. The technical advances produced through this project will include developing new algorithms, and combining new and existing data types, for the exploration of the microbial world. Building on principles shared between biology and computer science, the project will contribute to advances in knowledge extraction and graph analysis. Through education and outreach having hands-on lab activities the project will enhance bioinformatics education of undergraduates, urban high school students, and community lab members, while training postdocs to teach effectively. Technical summary: Limited resolution of microbial taxonomy with regard to molecular functionality, calls for novel, fast, and reliable classifications, capturing microbial processes, diversity, and interactions. Researchers will computationally analyze existing microbial genomic data using a new metric of whole-organism molecular function similarity. Using this similarity metric, a new classification scheme will be built, defining microbial clades according to their functional capacities. This scheme will be reflective of heredity as well as other forms of genetic transfer and of environmental factors. This will also provide an opportunity to explore the influence of inheritance versus horizontal gene transfer in acquiring new functions. Based on the consistent co-occurrence of functions in microorganisms, common molecular pathways and minimal pathways required for life within specific environmental niches will be elucidated. The power of this approach is its ability to assign proteins to pathways that remain experimentally uncharacterized. Overlaying available annotations of microorganism habitat preferences (e.g. temperature, oxygen requirements, and pH), broadly explains metabolic end-points and unique environmental adaptations. The newly developed tools will be used to describe niche-specific microbiomes for precise analysis of the environmental effects, whether in natural processes or for synthetic function design and industrial process optimization. The specific goals of the project include: (i) develop a function-based organism similarity metric, facilitating a functional clade definition, (ii) identify core sets of functions most discriminative of clade assignment and, thus, most descriptive of environment requirements and (iii) enable fast and accurate metagenome diversity and functional ability analysis. All tools and other resources will be publicly accessible at www.bromberglab.org/services. Students will be included in formulating relevant scientific questions and trained in methods for answering them through the building, evaluating, and applying computational methods. Two postdocs will be trained to conduct this research and in educational methods for leading an associated course, the first bioinformatics methods design course at this institution. Undergraduate students will (i) acquire skills in quantitative biology for which (ii) impact will be measured for both understanding of bioinformatics and perception of research as a whole. The postdocs will assist in outreach activities at a New York City high school and at Genspace - New York City's community biolab.

微生物在地球上占主导地位。微生物在环境压力的压力下进化，例如气候变化和污染；这些变化具有全球影响。对于微生物及其社区（或微生物组），了解大规模变化对微生物的后果要求我们了解它们在正常条件下的起点。在该项目中，将定义普通基线，以显示社区和环境中微生物的功能能力。微生物将分为相似的功能类别，两个类之间的“距离”将包括其功能能力的所有差异，这表明其在现有条件下的生活方式偏好。这样，微生物类成为一小部分共享功能，并且是推断微生物和微生物组多样性的新方法的基础。共享功能将作为发现新功能途径或已知途径的新成员的指南，这可能会在许多工业应用中产生更大的影响。通过该项目产生的技术进步将包括开发新算法，并将新的和现有的数据类型结合起来，以探索微生物世界。在生物学和计算机科学之间共享的原则的基础上，该项目将有助于知识提取和图形分析的进步。通过教育和宣传活动，该项目将增强本科生，城市高中生和社区实验室成员的生物信息学教育，同时培训博士后有效地教书。技术摘要：关于分子功能的微生物分类法的分辨率有限，需要新颖，快速和可靠的分类，捕获微生物过程，多样性和相互作用。研究人员将使用全新有生物分子功能相似性的新度量来计算现有的微生物基因组数据。使用此相似性度量，将建立一个新的分类方案，并根据其功能能力定义微生物进化枝。该方案将反映遗传性以及其他形式的遗传转移和环境因素。这还将提供一个机会，探索遗传与水平基因转移在获取新功能中的影响。基于微生物中功能的一致性同时出现，将阐明特定环境壁ches中所需的共同分子途径和生命所需的最小途径。这种方法的力量在于它可以将蛋白质分配到保持实验未表征的途径的能力。覆盖微生物栖息地偏好（例如温度，氧气需求和pH）的可用注释，可以广泛解释代谢终点和独特的环境适应。新开发的工具将用于描述特定于小众特异性的微生物组，以精确分析环境效应，无论是在自然过程中还是合成功能设计和工业过程优化。该项目的具体目标包括：（i）开发基于功能的生物体相似性度量，促进了功能性进化枝的定义，（ii）确定对进化枝分配的核心功能集，因此，对环境需求的描述性最大，并且（iii）启用快速，准确的元基因组多样性多样性和功能能力分析。所有工具和其他资源将在www.bromberglab.org/services上公开访问。学生将被包括在制定相关科学问题中，并接受通过建筑物，评估和应用计算方法来回答他们的方法的培训。将培训两个博士后，以进行这项研究和教育方法，以领导相关课程，即该机构的首个生物信息学方法设计课程。本科生将（i）获得定量生物学的技能，该技能（ii）将衡量对生物信息学和整个研究的看法的影响。博士后将在纽约市高中和纽约市社区Biolab的Genspace协助外展活动。