OSIB:RUI: Elucidating the cell biology and developmental regulation of sporogenesis and spore dimorphism in the microsporidia Nosema ceranae using a novel flow cytometry approach

OSIB:RUI：使用新型流式细胞术方法阐明微孢子虫微孢子虫孢子发生和孢子二态性的细胞生物学和发育调控

• 批准号: 2243451
• 负责人: Jonathan Snow
• 金额: $ 41.91万
• 依托单位: Barnard College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2243451&HistoricalAwards=false
• 关键词: OSIB; RUI; Elucidating; cell; biology

Some microbial pathogens infecting humans and other animals important to human activities, such as honey bees are hard to study because of their complex life cycles, in which cells of many different life stages occur inside the cells of their hosts. In other areas of biology, a technology called flow cytometry has been used to identify and separate cells of different types from a complex mixture based on differential staining. This proposal shows evidence that flow cytometry can be used to isolate and quantify different life stages of a specific parasite that infects and harms honey bees and their colonies. Flow cytometry will be used to better understand host and parasite factors that influence the production of different parasite life stages and how each life stage impacts on the health of the host and spread of infection between hosts. In addition, undergraduate researchers will be supported and trained in flow cytometry and other technologies to prepare these students for careers that support the US bioeconomy.The study of obligate intracellular pathogens with complex life cycles is difficult because they cannot easily be reproduced outside the host and are challenging to isolate. These obstacles render many important avenues of scientific inquiry unachievable, especially in situations where both host and pathogen are non-model organisms for which limited or no species-specific molecular tools are available, leading to slowed scientific progress. Flow cytometry in conjunction with specialized cell dyes was developed as a strategy to advance the understanding of Nosema ceranae, a key pathogen of honey bees. The hypothesis is that this strategy will isolate and quantify N. ceranae life stages corresponding to two spore types with different developmental timing, distinct morphological attributes, and divergent infectious properties. Isolation of the spore types and their precursors will allow scientists to define the molecular architecture of cellular identity that contributes to their unique properties. Quantification of these spore types and their precursors during infection in bees will allow science to answer key questions about infection dynamics by defining environmental factors that govern the generation of the two spore types. Use of this technique promises to facilitate a number of new directions in microsporidia research. In addition, this work is the basis for identifying potential therapeutics to prevent or minimize Nosema infection of bees, an important pollinator.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.

一些微生物病原体感染了人类和其他对人类活动重要的动物，例如蜜蜂很难研究，因为它们的生命周期复杂，其中许多不同生命阶段的细胞发生在宿主的细胞内。在生物学的其他领域，一种称为流式细胞术的技术已用于基于差异染色来识别和将不同类型的细胞与复杂混合物分离。该提议显示了流式细胞仪可用于分离和量化特定寄生虫的不同生命阶段，该寄生虫感染并伤害蜜蜂及其菌落。流式细胞仪将用于更好地了解影响不同寄生虫生命阶段产生的宿主和寄生虫因素，以及每个生命阶段如何影响宿主之间的宿主健康和感染的传播。此外，将在流式细胞仪和其他技术方面为本科研究人员提供支持和培训，以使这些学生为支持美国生物经济的职业做好准备。这些障碍使科学询问的许多重要途径无法实现，尤其是在宿主和病原体都是非模型生物的情况下，有限或没有物种特异性分子工具可用，从而导致科学进步放缓。与专门细胞染料结合使用流式细胞仪是一种策略，以提高对蜜蜂的关键病原体Nosema Ceranae的理解。假设是，该策略将隔离和量化Ceranae生命阶段，这些阶段对应于两种具有不同发育时机，独特的形态属性和不同传染特性的孢子类型。分离孢子类型及其前体将使科学家能够定义有助于其独特特性的细胞身份的分子结构。蜜蜂感染期间这些孢子类型及其前体的量化将使科学通过定义控制两种孢子类型的生成的环境因素来回答有关感染动态的关键问题。这种技术的使用有望促进微孢子虫研究中的许多新方向。此外，这项工作是确定潜在的治疗剂以预防或最大程度地减少蜜蜂的肿瘤感染，这是一项重要的授粉媒介。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛影响的评估标准来通过评估来获得支持的。