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.

Project Narrative Many cases of infertility and miscarriages remain unexplained and poorly understood. This project aims to identify a long-neglected mechanism that contributes to these diseases by discovering the role of conserved sperm centriole protein POC1B in rabbits' fertility.