The Role of Rabbit POC1B inSperm Centrioles

兔 POC1B 在精子中心粒中的作用

• 批准号: 10578061
• 负责人: Tomer Avidor-Reiss
• 金额: $ 45.15万
• 依托单位: UNIVERSITY OF TOLEDO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578061
• 关键词: Animals; Belief; Cattle; Cells; Centrioles; Centrosome; Cilia; Clinical; Complex; Data; Development; Diagnostic; Disabled Persons; Disease; Distal; Embryo; Embryonic Development; Evolution; Exhibits; Fertility; Fertilization; Genetic; Goals; Head; Head and neck structure; Human; In Vitro; Infertility; Inherited; Knowledge; Left; Location; Maintenance; Male Infertility; Mammals; Maps; Mentors; Microscopy; Microtubule-Organizing Center; Microtubules; Modeling; Movement; Mus; Names; Organelles; Oryctolagus cuniculus; Paper; Physiological; Play; Positioning Attribute; Process; Property; Proteins; Reproductive Biology; Research; Rod; Role; Side; Signal Transduction; Site; Slide; Somatic Cell; Sperm Tail; Spermatids; Spermiogenesis; Spontaneous abortion; Structural Protein; Structure; Students; Swimming; Tail; Testing; Testis; Transferable Skills; Visualization; cell motility; developmental disease; experience; improved; in vivo; innovation; insight; interest; loss of function mutation; mutant; neglect; programs; sperm cell; superresolution microscopy; symposium; undergraduate student

Summary Centrioles are microtubule-based organelles that form the cell's centrosome (the cell's major microtubule organization center) and cilium (a subcellular compartment involved in both signaling and motility). A somatic cell typically has two centrioles. During sperm formation in many animals, including humans, the quantity of many centriolar proteins declines, and the structure of the sperm centrioles are modified. This process is known as centrosome reduction and was previously thought to result in the degeneration of at least one centriole in mammals, leaving the sperm with one or no centrioles. In contrast, the Avidor-Reiss lab has identified a subset of centriolar proteins that are maintained or enriched during sperm formation and reorganized into a second centriole with an atypical structure in non-murine mammals. The Avidor-Reiss lab has named this process "centriole remodeling." Evidence from the Avidor-Reiss lab suggests that centriole remodeling improves sperm functionality by defining sperm movement via regulating its tail-neck-head coordination. Therefore, identifying the mechanisms and functions of centriole remodeling and its roles in fertilization and infertility will open new horizons in the field of reproductive biology. Our long-term research goal is to gain an in-depth understanding of the long-neglected sperm centrioles, including their formation, maintenance, function, evolution, and, more importantly, their clinical implications. This project’s objective is to provide the first insights into the sperm’s sperm centriole's functions and uncover the mechanisms behind its formation. This project's central hypothesis is that POC1B is essential for DC rod formation and normal function. The specific aims are to (1) To determine DC rod movement during swimming; (2) To determine the Centriole Remodeling mechanism; (3) To map POC1B interactions with other rod components. This project innovatively subjects rabbit sperms for close study to achieve the specific aims. To study them, it uses state-of-the-art microscopy to directly visualize sperm movement and protein reorganization during centriole remodeling to account for the species-specific tail-neck-head coordination. This research is original because it is the first to study with a paradigm-shifting hypothesis on the role of sperm centrioles. This study will advance our understanding of centrioles in general, centriole remodeling mechanisms in particular, and reveal their roles during sperm formation. Ultimately, the knowledge gained from these studies will inform research, diagnostics, and treatments for unknown causes of male infertility, spontaneous abortion, and developmental diseases. Dr. Avidor-Reiss has over 20 years of experience mentoring undergrad students and has developed a mentoring paradigm based on student interests, teamwork, and transferable skills. Undergraduate student research is a central component of this program. The students will be mentored to produce accurate data, analyze it impartially, present it professionally in conferences, and author papers to disseminate their discoveries.

概括 中心元素是基于微管的细胞器，形成了细胞的中心体（细胞的主要微管 组织中心）和纤毛（涉及信号传导和运动性的亚细胞隔室）。一个躯体 细胞通常有两个中心元素。在包括人类在内的许多动物中的精子形成期间 许多中心蛋白会降低，并且精子中心蛋白的结构被修饰。这个过程是 被称为中心体减少，以前被认为导致至少一个 哺乳动物中心，使精子有一个或没有中心。相比之下，Avidor-Reiss实验室具有 确定了在精子形成期间保持或富集的中心蛋白的一部分 在非乳腺哺乳动物中重新组织为具有非典型结构的第二个中心。 Avidor-Reiss实验室 命名了这个过程“ Centriole重塑”。来自Avidor-Reiss实验室的证据表明Centriole 通过调节其尾颈头来定义精子运动，可以改善精子功能 协调。因此，确定Centriole重塑的机制和功能及其在 受精和不育将在生殖生物学领域开放新的视野。 我们的长期研究目标是深入了解长期结束的精子中心， 包括它们的形成，维护，功能，进化，更重要的是它们的临床意义。 该项目的目标是提供有关精子中心功能的首次见解，并揭露 其形成背后的机制。该项目的中心假设是POC1B对于直流杆至关重要 形成和正常功能。具体的目的是（1）在游泳过程中确定直流杆的运动； （2）确定中心重塑机制； （3）绘制与其他杆的poc1b相互作用 成分。该项目对兔子精子进行了仔细研究，以实现特定目标。到 研究它们，它使用最先进的显微镜直接可视化精子运动和蛋白质重组 在中心重塑期间，以说明规格特定的尾颈头协调。这项研究是 原来是因为它是第一个对精子中心元素作用的范式转移假设进行研究的研究。这 研究将尤其是我们对中心元素的理解，尤其是中心重塑机制， 并揭示其在精子形成过程中的作用。最终，从这些研究中获得的知识将告知 研究，诊断和治疗男性不育症，赞助商和 发育疾病。 Avidor-Reiss博士拥有超过20年的心理本科生的经验，并开发了一个 根据学生的兴趣，团队合作和可转移技能来指导范式。本科生 研究是该计划的核心组成部分。学生将被视为产生准确的数据， 公正地对其进行分析，在会议上专业地介绍它，并作者论文传播他们的论文 发现。