Why do bacteria make sterols?

为什么细菌会产生甾醇？

• 批准号: 1656637
• 负责人: Franco Basile
• 金额: $ 70万
• 依托单位: University of Wyoming
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1656637&HistoricalAwards=false
• 关键词: Why; do; bacteria; make; sterols

AbstractNaomi Ward, 1656637, Why do bacteria need sterols?Part I Non-technical: This project pursues a fundamental question in cell biology: why do bacteria make sterols? Sterols are lipid (fat) molecules that have multiple biological roles in eukaryotic (human, animal, and plant) cells. These roles include maintaining the structure and function of cell membranes. The best-known sterol is probably cholesterol. Sterols are also produced by some bacteria, but their purpose is unknown because bacterial cell membranes are not reported to need sterols. Discovering the purpose of bacterial sterols will make a significant contribution because knowledge of sterol function, in general, will be expanded. This is of broader relevance to society because of the fundamental importance of sterols as cellular building blocks, but also in more practical terms. For example, sterols such as cholesterol are essential in human physiology, and fungal sterol synthesis can be targeted by specific drugs to treat fungal infections. The project will also enhance the country's scientific workforce by providing cutting edge training in modern biological and analytical chemistry technologies. Part II Technical: The project goal is to determine the role of sterols in Gemmata obscuriglobus, the first bacterium in which sterols have been shown to be essential. G. obscuriglobus possesses a unique constellation of eukaryote-like, sterol-associated, cellular features, including budding replication, complex intracellular membranes, and endocytosis-like behavior. The central hypothesis is that that Gemmata sterols have an expanded functional repertoire relative to eukaryotic sterols, including known functions of sterols in eukaryotes, as well as novel functions specific to a bacterial cellular context. The rationale for the proposed research is that it will expand our functional and evolutionary understanding of sterols, and uncover overlaps in the roles of eukaryotic and prokaryotic sterols. The project objective will be achieved by pursuing the following Specific Aims: (1) Determine how G. obscuriglobus sterols support budding replication; (2) Identify the contribution of G. obscuriglobus sterols to endocytosis-like activity; (3) Establish the effect of sterols on phospholipid metabolism in G. obscuriglobus. Research methods include microscopy, proteomics, and lipidomics. The expected outcome of the project is an improved understanding of sterol function, and the potential contribution of sterols to bacterial membrane-mediated processes characteristic of eukaryotes, as well as novel functions specific to bacteria. This will have important positive impact because it will potentially reveal previously undetected similarities and differences in prokaryotic and eukaryotic cell structures and functions. Broader Impacts include the Microbestiary, a unique science-art education and outreach project, where microbes and their cell structures serve as the subject matter. Multiple education and outreach products, including K-12 participation, will be generated, and the Microbestiary will be incorporated into undergraduate teaching in the humanities and sciences. Participation in this project will provide interdisciplinary training in cell biology and analytical chemistry for graduate and undergraduate students, who will also be key personnel for creating and disseminating the Microbestiary.

摘要Naomi Ward，1656637，为什么细菌需要甾醇？第一部分非技术性：该项目探讨细胞生物学中的一个基本问题：为什么细菌会产生甾醇？甾醇是脂质（脂肪）分子，在真核（人类、动物和植物）细胞中具有多种生物学作用。这些作用包括维持细胞膜的结构和功能。最著名的甾醇可能是胆固醇。一些细菌也会产生甾醇，但其用途尚不清楚，因为没有报道细菌细胞膜需要甾醇。发现细菌甾醇的用途将做出重大贡献，因为一般来说，甾醇功能的知识将得到扩展。由于甾醇作为细胞构建模块的根本重要性，而且从更实际的角度来看，这与社会具有更广泛的相关性。例如，胆固醇等甾醇对于人体生理至关重要，而真菌甾醇的合成可以通过特定药物来靶向治疗真菌感染。该项目还将通过提供现代生物和分析化学技术的前沿培训来增强该国的科学队伍。第二部分技术：该项目的目标是确定甾醇在 Gemmata obscuriglobus 中的作用，Gemmata obscuriglobus 是第一种被证明甾醇在其中至关重要的细菌。 G. obscuriglobus 拥有一系列独特的真核生物样、甾醇相关的细胞特征，包括出芽复制、复杂的细胞内膜和类内吞作用的行为。中心假设是，相对于真核甾醇，Gemmata 甾醇具有扩展的功能库，包括真核生物中甾醇的已知功能，以及细菌细胞环境特有的新功能。拟议研究的基本原理是，它将扩展我们对甾醇的功能和进化的理解，并揭示真核和原核甾醇作用的重叠。该项目目标将通过追求以下具体目标来实现： (1) 确定 G. obscuriglobus 甾醇如何支持出芽复制； (2) 确定 G. obscuriglobus 甾醇对内吞样活性的贡献； (3) 确定甾醇对G. obscuriglobus 磷脂代谢的影响。研究方法包括显微镜、蛋白质组学和脂质组学。该项目的预期成果是更好地了解甾醇功能、甾醇对真核生物细菌膜介导过程特征的潜在贡献，以及细菌特有的新功能。这将产生重要的积极影响，因为它将有可能揭示原核和真核细胞结构和功能中以前未检测到的相似性和差异。更广泛的影响包括微生物寓言，这是一个独特的科学艺术教育和推广项目，以微生物及其细胞结构为主题。将产生包括K-12参与在内的多种教育和推广产品，并将微生物寓言纳入人文和科学的本科教学中。参与该项目将为研究生和本科生提供细胞生物学和分析化学方面的跨学科培训，他们也将成为创建和传播微生物动物界的关键人员。

项目成果

Essentiality of sterol synthesis genes in the planctomycete bacterium Gemmata obscuriglobus

• DOI: 10.1038/s41467-019-10983-7
• 发表时间: 2019-07
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: Elena Rivas-Marín;Sean Stettner;Ekaterina Y. Gottshall;Carlos Santana-Molina;M. Helling;F. Basile;N. Ward;D. Devos