Excellence in Research: The Role of Bovine Sperm Acrosome in Fertilization

卓越研究：牛精子顶体在受精中的作用

• 批准号: 2153783
• 负责人: Subir Nagdas
• 金额: $ 36.22万
• 依托单位: Fayetteville State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2153783&HistoricalAwards=false
• 关键词: Excellence; Research; Role; Bovine; Sperm

This project will elucidate the role of certain proteins in the activation of the acrosome in cows. The acrosome is a small compartment in sperm cells that releases enzymes to allow the sperm to penetrate the protective layer surrounding the egg. The PI has characterized two novel proteins in the acrosome, and will characterize the function and ability of these proteins to bind to calcium and to bind to other acrosomal proteins to form a complex that activate the acrosome just prior to fertilization. This project will provide increased understanding of fundamental aspects of mammalian fertilization, as well as contributing to improved strategies for maintaining and activating stored spermatozoa and improving fertilizing capacity of stored sperm for needs of agriculture, zoological preservation, and reproductive health. The projects will also increase opportunities for undergraduates and high school students at this HBCU to learn the ethics of science and receive hands-on experience/skills with modern biochemical and cell biological techniques. Most of the PI's previous lab students have since matriculated into various graduate and professional programs. The results of this project will thereby increase the pool of future Ph.D. scientists from underrepresented groups, as well as facilitate high school students' admission into research-intensive schools for baccalaureate programs. The calcium-dependent acrosome reaction is a key control point in mammalian fertilization, but numerous unresolved signaling events and biochemical mechanisms that promote membrane fusion of the acrosome to the sperm plasma membrane remain poorly understand. The goal of this project is to identify the biochemical mechanisms that regulate the role of acrosomal proteins in membrane fusion and the release of hydrolases during the acrosome reaction of bovine sperm. The PI’s work has characterized a 32kDa acrosomal polypeptide (OMC32) essential for membrane fusion that is present in the bovine sperm acrosome. The project here will examine the hypothesis that OMC32 interacts with other acrosomal proteins to regulate release of hydrolases and other acrosomal proteins essential to completing the acrosome regulation, and whether OMC32 is an essential target of signal transduction elements and regulatory proteins that mediate the acrosome reaction. In a second aim, the PI and students will examine a novel 64kDa calcium-binding protein in the outer acrosomal membrane. Here, the project will test the hypothesis that this calcium-binding protein regulates fusion between the acrosomal membrane and the sperm plasma membrane. Besides extensive training of high school and undergraduate students in research as a career, this project will contribute to greater understanding of sperm membrane fusion, acrosome integrity and function, and mammalian fertilization. The results may also contribute to improved strategies for maintaining acrosomal integrity in stored spermatozoa, and improving the fertilizing capacity of mammalian spermatozoa, with potential benefits of maintaining stock for the cattle industry, for endangered mammal species, as well as for human reproductive health.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.

本项目将阐明某些蛋白质在奶牛顶体激活中的作用。 顶体是精子细胞中的一个小隔间，它释放酶，使精子能够穿透卵子周围的保护层。 PI已经表征了顶体中的两种新型蛋白质，并将表征这些蛋白质与钙结合并与其他顶体蛋白结合以形成在受精前激活顶体的复合物的功能和能力。 该项目将提供更多的哺乳动物受精的基本方面的理解，以及有助于改善战略，以保持和激活存储的精子和提高存储的精子的能力，农业，动物保护和生殖健康的需要。 这些项目还将增加本科生和高中生在HBCU学习科学伦理学的机会，并获得现代生物化学和细胞生物学技术的实践经验/技能。 PI以前的大多数实验室学生已经进入了各种研究生和专业课程。 该项目的结果将增加未来博士的储备。该项目旨在帮助来自代表性不足群体的科学家，并为高中生进入研究密集型学校攻读学士学位课程提供便利。钙依赖性顶体反应是哺乳动物受精过程中的关键控制点，但促进顶体与精子质膜膜融合的许多未解决的信号事件和生化机制仍然知之甚少。 本项目的目标是确定调节顶体蛋白在膜融合中的作用的生化机制，以及牛精子顶体反应过程中水解酶的释放。PI的工作已经表征了存在于牛精子顶体中的膜融合所必需的32 kDa顶体多肽（OMC 32）。 该项目将检验OMC 32与其他顶体蛋白相互作用以调节完成顶体调节所必需的水解酶和其他顶体蛋白的释放的假设，以及OMC 32是否是介导顶体反应的信号转导元件和调节蛋白的重要靶点。 在第二个目标中，PI和学生将检查外顶体膜中的一种新的64 kDa钙结合蛋白。 在这里，该项目将测试的假设，这种钙结合蛋白调节顶体膜和精子质膜之间的融合。 除了对高中生和本科生进行广泛的研究培训外，该项目还将有助于更好地了解精子膜融合，顶体完整性和功能以及哺乳动物受精。 这些结果也可能有助于改善维持储存精子顶体完整性的策略，并提高哺乳动物精子的繁殖能力，为养牛业、濒危哺乳动物物种、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智力价值和更广泛的影响审查标准。