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.

摘要 中心粒是以微管为基础的细胞器，形成细胞的中心体(细胞的主要微管 纤毛(一个同时参与信号和运动的亚细胞室)。一个躯体 细胞通常有两个中心粒。在包括人类在内的许多动物的精子形成过程中， 许多中心粒蛋白减少，精子中心粒的结构发生改变。这个过程是 称为中心体减少，以前被认为会导致至少一个 哺乳动物体内的中心粒，使精子只有一个中心粒或没有中心粒。相比之下，Avidor-Reiss实验室 确定了一组中心粒蛋白，它们在精子形成过程中保持或丰富，并 在非小鼠哺乳动物中重组为具有非典型结构的第二个中心粒。Avidor-Reiss实验室 将这一过程命名为“中心粒重塑”。来自Avidor-Reiss实验室的证据表明，中心粒 重塑通过调节精子的尾颈头来定义精子的运动，从而改善精子的功能 协调。因此，确定中心粒重塑的机制和功能及其在 受精和不孕将开辟生殖生物学领域的新天地。 我们的长期研究目标是深入了解长期被忽视的精子中心粒， 包括它们的形成、维持、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对精子中心粒功能的第一次洞察，并揭示 其形成背后的机制。该项目的中心假设是POC1B对于DC棒是必不可少的 队形和正常功能。具体目的是：(1)确定直流杆在游泳过程中的运动； (2)确定中心粒重塑机制；(3)绘制POC1B与其他杆的相互作用图 组件。该项目创新性地对兔子精子进行近距离研究，以实现特定的目标。至 对它们进行研究，它使用最先进的显微镜直接显示精子的运动和蛋白质重组 在中心粒重塑期间，以解释物种特定的尾颈-头协调。这项研究是 原创是因为它是第一个研究精子中心粒作用的范式转换假说。这 研究将促进我们对中心粒总体上的理解，特别是中心粒重塑机制， 并揭示了它们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有助于 研究、诊断和治疗不明原因的男性不育、自然流产和 发育性疾病。 Avidor-Reiss博士有20多年指导本科生的经验，并开发了一种 基于学生兴趣、团队合作和可转移技能的指导模式。本科生 研究是这个项目的核心组成部分。学生们将在指导下产生准确的数据， 不偏不倚地分析它，在会议上专业地展示它，并撰写论文来传播他们的 发现。