MTM1: Network properties of fungal-bacterial interactions: Predictive modeling and functional analysis of the Hawaiian Drosophila gut microbiome
MTM1:真菌-细菌相互作用的网络特性:夏威夷果蝇肠道微生物组的预测建模和功能分析
基本信息
- 批准号:2025669
- 负责人:
- 金额:$ 50万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-10-01 至 2024-09-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
How an animal develops, reproduces, and adapts to its environment depends upon not only the traits encoded by its genome, but, as well, the contributions of its microbiome. In many microbial communities, the interactions between bacteria and fungi have profound effects on community properties and host physiology. However, little is known about the mechanisms by which interactions between kingdoms contribute to a healthy microbiome and promote host fitness. This proposal seeks to understand the role of bacterial-fungal interactions in the host physiology of Drosophila (pomace flies) from the Hawaiian clade. Hawaiian flies have adapted to a wide range of environments and lifestyles. The remarkable diversity of Hawaiian Drosophila ecology together with the relatively simple mix of bacterial and fungal species found in their gut provide an excellent system for understanding how microbes help host animals adapt to diverse habitats and diets, potentially catalyzing the evolution of new species. Elucidating the basic principles that govern microbe-microbe and microbe-host interactions holds promise for the development of novel antimicrobial treatments and improving the cultivation of agricultural products. The findings of the proposed project will have broad applicability to the conservation of endangered native Hawaiian fauna (including Drosophila) by identifying microbe-related strategies that will improve host health and survival. The University of Hawai‘i and Chaminade University of Honolulu are minority-servicing institutions with Native Hawaiian students comprising, respectively, 16.5% and 19% of the student body. Involving students from underserved populations with data science and microbiology methods, including the tools developed for this project, will increase the pool of trained scientists in the region and encourage multi-generational Native Hawaiian engagement with STEM.The central hypothesis of this proposal is that bacterial-fungal interactions benefit host fitness by stabilizing the microbiome and enhancing host metabolic processes. Preliminary work using in silico network modeling, high throughput amplicon sequencing data, and microbial manipulation experiments reveal that i) bacterial and fungal members in the gut of Hawaiian flies are likely to interact based on their patterns of co-occurrence; and ii) fungal function is critical for host fitness. The central hypothesis will be addressed with the following approaches: first, computational tools will be generated to allow robust prediction of microbial interactions and emergent community phenotypes such as stability, growth, and resilience to pathogens. Second, bacterial and fungal species will be isolated from native Hawaiian Drosophila guts and cultured in isolation or in pairwise combinations. Metabolomic profiling and measurements of community properties under normal and stressed conditions will be used to identify differences between mixed and pure communities as well as beneficial and deleterious combinations. The data will be used to refine and validate in silico models. Finally, the effect of interkingdom interactions on host physiology will be determined by inoculating Drosophila with various microbial combinations and measuring the impact on host metabolite profile and life history features such as fertility, stress resistance, and lifespan. Metabolomic data will be used to identify candidate pathways underlying microbial-host interactions.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.
动物如何发育、繁殖和适应环境不仅取决于其基因组编码的特征,还取决于其微生物组的贡献。在许多微生物群落中,细菌和真菌之间的相互作用对群落特性和宿主生理有着深远的影响。然而,关于王国之间的相互作用有助于健康的微生物组和促进宿主适应性的机制知之甚少。该建议旨在了解细菌-真菌相互作用在夏威夷分支果蝇(果渣蝇)宿主生理学中的作用。夏威夷苍蝇已经适应了广泛的环境和生活方式。夏威夷果蝇生态的显著多样性,以及在其肠道中发现的相对简单的细菌和真菌物种的混合,为了解微生物如何帮助宿主动物适应不同的栖息地和饮食提供了一个很好的系统,可能会催化新物种的进化。阐明控制微生物-微生物和微生物-宿主相互作用的基本原理为开发新型抗菌剂治疗和改善农产品的种植提供了希望。拟议项目的研究结果将广泛适用于保护濒危的夏威夷本土动物(包括果蝇),确定微生物相关的战略,将改善主机的健康和生存。夏威夷大学和檀香山查米纳德大学是为少数民族服务的机构,夏威夷土著学生分别占学生总数的16.5%和19%。让来自服务不足人群的学生参与数据科学和微生物学方法,包括为此项目开发的工具,将增加该地区训练有素的科学家的数量,并鼓励多代夏威夷土著参与STEM。该提案的核心假设是细菌-真菌相互作用通过稳定微生物组和增强宿主代谢过程来有益于宿主健康。使用计算机网络建模、高通量扩增子测序数据和微生物操作实验的初步工作揭示了i)夏威夷果蝇肠道中的细菌和真菌成员可能基于其共存模式相互作用;以及ii)真菌功能对于宿主适应性至关重要。中心假设将通过以下方法来解决:首先,将生成计算工具,以允许对微生物相互作用和新兴群落表型(如稳定性、生长和对病原体的恢复力)进行稳健预测。第二,将从夏威夷原生果蝇肠道中分离细菌和真菌物种,并单独或成对组合培养。代谢组学分析和测量正常和应激条件下的社区属性将被用来确定混合和纯社区之间的差异,以及有益和有害的组合。这些数据将用于完善和验证计算机模型。最后,将通过将果蝇与各种微生物组合并测量对宿主代谢产物谱和生活史特征(如生育力、抗应激性和寿命)的影响来确定界间相互作用对宿主生理学的影响。代谢组学数据将用于确定潜在的微生物-宿主相互作用的候选途径。该奖项反映了NSF的法定使命,并被认为值得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来支持。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Joanne Yew其他文献
Joanne Yew的其他文献
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{{ truncateString('Joanne Yew', 18)}}的其他基金
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2211994 - 财政年份:2022
- 资助金额:
$ 50万 - 项目类别:
Continuing Grant
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