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RESEARCH

Centrosome

Centrosomes are the major microtubule organizing centers, which consist of centriolar cores surrounded by a proteinaceous matrix known as pericentriolar material (PCM). 

Centrosome description
Midori Ohta, OIST

Centrioles, ancient cell organelles, duplicate once per cell cycle in a process reminiscent of DNA replication. During cell division, centrioles organize the PCM matrix, which recruits microtubule nucleating factors and catalyzes spindle assembly, ensuring accurate chromosome segregation. In differentiated cells, centrioles act as templates for cilia and flagella formation, structures critical for cell motility and signaling. Our group investigates the regulatory mechanisms underlying centriole function and the molecular evolution enabling these dual roles.

Centrosome Cycle
Midori Ohta, OIST

Centrosome Regulation in Sexual Reproduction

Despite their critical role in cell division, centrioles are eliminated during oogenesis in most animals, leaving chromosomes to be segregated by an acentriolar spindle. During fertilization, centrioles are reintroduced by sperm. This elimination of centrioles in oocytes is thought to be essential for maintaining the correct centriole number in the zygote; however, the underlying mechanism and biological significance remain unclear. Our group aims to elucidate the mechanisms controlling centriole elimination in oocytes by combining cell biology with biochemical reconstitutions of the protein machinery.

Centrosome Regulation in Oogenesis
Midori Ohta, OIST

Biochemical Reconstitution of Centrosomal Protein Machinery

Centrioles are large macromolecular complexes that comprise the core of centrosomes and organize the proteinaceous PCM matrix. While the amino acid sequences of centrosome components diverge across species, the centriole structure with nine-fold symmetry and the protein architecture of the key regulatory subunits are well conserved, highlighting the significance of structural understanding. The goal of our group is to recapitulate the essential process of centrosome assembly and disassembly through biochemical reconstitution and to elucidate their molecular structures and mechanisms.

Centriole Evolution

In many animals, centrioles originate from the basal body of sperm flagella. Then, what is the evolutionary origin of centrioles? How did centrioles evolve to perform two distinct functions: chromosome segregation and cilia/flagella formation? It has been proposed that the basal body, initially responsible for flagellum formation, gave rise to the centrosome (centriole + PCM), which orchestrates chromosome segregation. However, the mechanisms underlying this evolutionary transition remain unclear. By establishing new marine model organisms and comparing the molecular mechanisms of centrosome assembly across species, our research aims to uncover the molecular basis of centriole evolution, enabling its dual function.

Centrosome Regulation in Cell Division

Work over the past three decades has established the molecular framework for centrosome assembly and regulation. However, many fundamental questions remain: How are centrosomes activated during cell division? How is the number of centrosomes precisely regulated? Employing gene engineering and live-cell imaging in the C. elegans system and human cell culture, we aim to address these questions.

Midori Ohta, OIST