Grant: CIHR Fellowship

Cell-to-cell fusion is critical for human development and health. For example, in the event of fertilization, a sperm and an egg meet and fuse together to become one cell that develops into a fetus. Similarly, many organs, such as muscle, bone and placenta, are established by cell-cell fusion. Such fusion events have been also observed in cancer, wounded and immune cells. However, we know very little about cell-cell fusion mechanism. If we do, we may be able to alter it to cure or enhance such human conditions. Fruit fly embryos contain muscle progenitor cells that also fuse to make muscle, and it has been an excellent organismal model to study cell-cell fusion with the powerful genetic tools available in this system. Studies using fruit fly embryos have identified several evolutionarily-conserved genes required for muscle progenitor cell fusion, but more fusion regulators are yet to be discovered. However, when identifying and examining the fusion regulators in embryos, conventional genetic approaches, such as mutant embryo analysis, are often hampered by the normal gene products inherited from the mother fruit fly. Intriguingly, the recent development of "optogenetics" has enabled light-inducible protein disruption using genetically-inserted light-responsive tags. My goal is to implement this optogenetic tools to remove protein function precisely when and where needed in fruit fly embryos. I will first show the effectiveness of the two distinct optogenetic strategies by disrupting a novel fusion protein in fruit fly embryos. I will compare the resulting effect of light-induced protein disruption to the mutant embryos. Then, I will apply optogenetics to disrupt other potential fusion regulators, whose mutant embryo analysis may have suffered from its essential maternal contribution. This revolutionary approach will greatly facilitate cell fusion studies, but more importantly, it will represent a unique enabling technology for broad fruit fly research community.