Researchers NAKAJIMA Kohdai


Research Fellow,

The University of Tokyo


Higashiyama Group

The University of Tokyo, Technion - Israel Institute of Technology


Podbilewicz Lab

Research Fields
Molecular Biology, Cell Biology
Fertilization, Cell-Cell Fusion

Exploration of C.elegans novel fusion related molecules and live imaging based unveiling molecular regulation mechanism

Cell-cell fusion is essential for fertilization, organ development and possibly the origin of eukaryotes. This process requires specialized membrane-bound fusion proteins called fusogens, which mediate and allow the exchange of contents between cells. So far, the host lab, Podbilewicz’s lab, discovered a structural homology between different classes of fusogens: gamete fusogens (i.e. Arabidopsis GCS1/HAP2), somatic fusogens (fusion family [FF] EFF-1 and AFF-1), viral class II fusogens (e.g. Dengue virus E glycoprotein) and archaeal fusogens (i.e. Fusexin1). These sexual, somatic, viral, and archaeal fusogens are functionally, structurally, and evolutionarily conserved and were named Fusexins. However, it still remains to be elucidated how cell membrane could adhere and fuse through their molecular interaction. To unveil the action mechanism of the fusion machinery complex(es) that are responsible for adhesion and fusion in fertilization and development, I propose to use the nematode Caenorhabditis elegans (C. elegans) as a model organism. In C. elegans, twelve genes that are required for late stages in fertilization have been found so far, however to date none were characterized as bona fide fusogens. Additionally, some of the genes involved in mouse fertilization have homologs in C. elegans, whose function is not clear, presenting an exciting opportunity to discover shared and divergent functions in fertilization mechanisms across evolution. C. elegans has two somatic fusogens, EFF-1 and AFF-1, which were proposed to interact with one another in trans using a cell culture heterologous system. However, such cross-interaction in vivo was not noted during normal development. In order to understand cell-cell fusion mechanisms during fertilization and development, it is indispensable not only to identify new players but also to elucidate the action mechanism of known fusogens. Therefore, my main objective is to identify novel fusion-related molecules in fertilization and development and elucidate the molecular dynamics of cell-cell fusion in C. elegans. My hypothesis is that cell-cell fusion is achieved by the orchestrated interaction of fusogens and adhesion molecules. In this context, I will identify the novel fusion-related molecules using bioinformatics and genetics and investigate its spatiotemporal molecular dynamics using live imaging.

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