New Tools to Access the Fungal Metabolome and its Ecological Function

获取真菌代谢组及其生态功能的新工具

• 批准号: 1808717
• 负责人: Sandra Loesgen
• 金额: $ 42.82万
• 依托单位: Oregon State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2020-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1808717&HistoricalAwards=false
• 关键词: New; Tools; Access; Fungal; Metabolome

With this?award, the Chemistry of Life Processes?Program in the Chemistry Division is supporting?Dr. Sandra Loesgen?from Oregon State University to examine the chemical structure and ecological function of compounds produced by fungi. Fungi are critical members of most ecosystems. Many fungi produce a diversity of secondary metabolites, chemical compounds that have important roles in their defense, communication between individuals of the same species, and communication between different species. Fungal secondary metabolites have also been used by humans for biomedical and agricultural applications, such as the antibiotic penicillin, the fungicide strobilurin, and the immunosuppressant cyclosporin. However, identifying these compounds and understanding their ecological function remains difficult and labor intensive. This research project aims to implement new approaches for isolating and studying the chemicals produced by fungi, using methods including gene activation and metabololite profiling. These experiments contribute to an improved understanding of the complex chemical ecology of fungi. This work also has potential to identify novel secondary metabolites with practical applications. The Loesgen Lab regularly participates in OSU's Discovery Days, a semiannual education fair that serves 3500 children from schools around Oregon. This project expands the lab's collaboration with the Oregon Museum of Science and Industry (OMSI) and establishes an interactive exhibit that introduces children and their parents to natural products chemistry. Microbial chemistry is an interdisciplinary field with important ecological applications, and is thus very well positioned to serve as a vehicle for chemistry education. This team participates in the Chemistry Undergraduate Mentorship and Empowerment (ChUME) Initiative atOSU. ChUME enhances undergraduate student success by providing students with a strong professional support network and personal mentoring.Three prominent challenges in modern microbial chemistry are driving expression of silenced gene clusters, identifying novel secondary metabolites, and understanding the ecological role of identified compounds. Dr. Loesgan and her group will study the environmental, chemical, and epigenetic perturbation in fungi to access previously repressed secondary metabolites. They will investigate metabolomics methods used to rapidly identify newly expressed natural products and integrate metabolomics methods with bioassay data to enable the elucidation of the ecological role of secondary metabolites. Aim 1 establishes a method for de-repressing gene clusters using a novel class of chemical epigenetic modifying agents. Aim 2 uses metabolomics methods to analyze liquid chromatography mass spectrometry (LCMS), high performance two-dimensional NMR, and RNA expression data in order to detect and isolate newly expressed secondary metabolites. Aim 3 tests secondary metabolites for effects on bacterial, fungal, and plant growth in order to determine the likely ecological role of these molecules.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

用这个？生命过程化学奖化学系的课程是支持的吗？桑德拉·勒斯根医生来自俄勒冈州州立大学的研究人员研究了真菌产生的化合物的化学结构和生态功能。真菌是大多数生态系统的重要成员。许多真菌产生多种次级代谢产物，这些化合物在其防御，同一物种个体之间的通信以及不同物种之间的通信中发挥重要作用。真菌次级代谢产物也被人类用于生物医学和农业应用，如抗生素青霉素、杀真菌剂嗜球果伞素和免疫抑制剂环孢菌素。然而，识别这些化合物并了解它们的生态功能仍然很困难，而且需要大量劳动。该研究项目旨在采用新方法分离和研究真菌产生的化学物质，使用包括基因激活和代谢物分析在内的方法。这些实验有助于提高对真菌复杂化学生态学的理解。这项工作也有可能确定新的次生代谢产物与实际应用。 Loesgen实验室定期参加OSU的发现日，这是一个半年度的教育博览会，为来自俄勒冈州各地学校的3500名儿童提供服务。该项目扩大了实验室与俄勒冈州科学与工业博物馆（OMSI）的合作，并建立了一个互动展览，向儿童及其父母介绍天然产品化学。微生物化学是一个具有重要生态应用的跨学科领域，因此非常适合作为化学教育的载体。该团队参加了俄勒冈州立大学的化学本科生导师和授权（ChUME）计划。ChUME通过为学生提供强大的专业支持网络和个人指导来提高本科生的成功率。现代微生物化学中的三个突出挑战是驱动沉默基因簇的表达，鉴定新的次级代谢产物，以及了解已鉴定化合物的生态作用。Loesgan博士和她的团队将研究真菌中的环境、化学和表观遗传扰动，以获得以前被抑制的次级代谢产物。他们将研究用于快速识别新表达的天然产物的代谢组学方法，并将代谢组学方法与生物测定数据相结合，以阐明次级代谢产物的生态作用。目的1建立一种利用一类新的化学表观遗传修饰剂去抑制基因簇的方法。目的2利用代谢组学方法分析液相色谱质谱（LCMS）、高效二维NMR和RNA表达数据，以检测和分离新表达的次级代谢产物。目标3测试次级代谢物对细菌、真菌和植物生长的影响，以确定这些分子可能的生态作用。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。