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.

一些感染人类和其他对人类活动很重要的动物（如蜜蜂）的微生物病原体很难研究，因为它们的生命周期很复杂，其中许多不同生命阶段的细胞发生在宿主细胞内。在生物学的其他领域，一种名为流式细胞术的技术已用于根据差异染色从复杂混合物中识别和分离不同类型的细胞。该提案表明，流式细胞术可用于分离和量化感染和危害蜜蜂及其群体的特定寄生虫的不同生命阶段。流式细胞术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的健康和宿主之间的感染传播。此外，本科生研究人员将获得流式细胞术和其他技术的支持和培训，为这些学生从事支持美国生物经济的职业做好准备。具有复杂生命周期的专性细胞内病原体的研究很困难，因为它们不容易在宿主外繁殖，并且分离具有挑战性。这些障碍使得许多重要的科学探索途径无法实现，特别是在宿主和病原体都是非模式生物的情况下，针对这些生物的物种特异性分子工具有限或根本没有，导致科学进展缓慢。流式细胞术结合专门的细胞染料被开发为一种策略，以促进对蜜蜂的关键病原体---微孢子虫的了解。假设这种策略将分离和量化N。两种孢子类型具有不同的发育时间、不同的形态属性和不同的感染特性。孢子类型及其前体的分离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。这些孢子类型及其前体在蜜蜂感染期间的定量将使科学能够通过定义控制两种孢子类型产生的环境因素来回答有关感染动力学的关键问题。该技术的应用有望为微孢子虫的研究开辟新的方向。此外，这项工作是确定潜在的治疗方法，以防止或尽量减少微孢子虫感染蜜蜂，一个重要的授粉者的基础。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。