Laboratory for Bottom-up Cell Biology

Cells sustain life through the dynamic assembly and disassembly of diverse subcellular structures, each built from molecular components and endowed with distinct biological functions. A central and non-trivial question in biology is how microscopic molecules sense the vast intracellular space and self-organize, with precise spatial and temporal control, into micrometer-scale structures that regulate cellular functions. Addressing this question requires an integrated understanding of biochemical reactions and physical interactions across multiple length and time scales.

Our laboratory aims to uncover the design principles governing the emergence of cell-scale ordered structures and biological functions from molecular components. Using the cytoskeleton as a model system, we investigate the biochemical and physical conditions under which cytoskeletal architectures and associated functions can be reconstituted in artificial cells. By combining in vitro reconstitution, advanced microscopy, and physical modeling, we seek to bridge molecular-level mechanisms and cellular-scale behaviors.

Recently, we established a novel optogenetic tool that directly manipulates actin network assembly by activating the Arp2/3 complex, and demonstrated that actin network density regulates the activities of actin-binding proteins. We also determined the kinetic scheme of myosin activation through phosphorylation by ZIP kinase, one of the major myosin kinases, providing quantitative insight into the regulation of actomyosin contractility. In addition, we quantitatively analyzed the effects of lipid composition on the production yield of cell-sized liposomes generated using the inverted emulsion technique, which has been extensively utilized to create artificial cells. Building on these findings, we successfully reconstituted an active actin cortex inside cell-sized liposomes that exhibit membrane protrusions known as blebs, providing physical insights into amoeboid cell migration. These studies advance our understanding of how the actin cytoskeleton regulates cellular functions and contribute to the development of experimental platforms and technologies in synthetic biology.