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

这个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，它释放酶让精子穿透卵子周围的保护层。PI已经鉴定了顶体中的两个新的蛋白质，并将表征这些蛋白质与钙结合的功能和能力，以及与其他顶体蛋白结合形成的复合体，在受精前激活顶体。该项目将提供对哺乳动物受精基本方面的更多了解，并有助于改进保存和激活储存精子的战略，并提高储存精子的受精能力，以满足农业、动物保护和生殖健康的需要。这些项目还将增加该HBCU的本科生和高中生学习科学伦理的机会，并获得现代生化和细胞生物学技术的实践经验/技能。自那以后，PI以前的大多数实验室学生都进入了各种研究生和专业课程。因此，该项目的成果将增加来自代表性不足群体的未来博士科学家的人数，并促进高中生进入研究密集型学校攻读学士学位课程。钙依赖的顶体反应是哺乳动物受精过程中的一个关键控制点，但促进顶体与精子质膜融合的众多信号转导事件和生化机制尚不清楚。本项目的目标是确定在牛精子顶体反应过程中，顶体蛋白在膜融合和水解酶释放中的作用的生化机制。PI的工作描述了牛精子顶体中存在的一种对膜融合至关重要的32 kDa顶体多肽(OMC32)。该项目将检验OMC32与其他顶体蛋白相互作用以调节水解酶和其他完成顶体调节所必需的顶体蛋白的释放的假设，以及OMC32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和学生们将检测顶体外膜中一种新的64 kDa钙结合蛋白。在这里，该项目将测试这种钙结合蛋白调节顶体膜和精子质膜之间融合的假设。除了作为职业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。这些结果还可能有助于改进策略，以保持储存精子的顶体完整性，并提高哺乳动物精子的受精能力，潜在的好处是为养牛业、濒危哺乳动物物种以及人类生殖健康保持种群。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.