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Our lab researches two major topics: DNA repair proteins and cell mechanobiology.
Research on DNA repair proteins focuses on DNA stability, the stress exerted on the cell genome during replication, and mechanisms for detecting DNA damage. Research on cell mechanobiology is focused on receptors that promote phagocytosis and synthetic substances involved in phagocytosis.
Several enzymes such as polymerase and helicase are involved in the gene expression process. Studying the interaction between these enzymes and nucleic acids is very important for elucidating the principles of regulation of gene expression. By observing the actions of nucleic acids and proteins at the molecular level, we aim to uncover gene regulation functions that cannot be identified through cellular-level research. To observe nucleic acids and proteins, our laboratory uses single molecule fluorescence resonance energy transfer(smFRET) technology. When two fluorescent substances that act as an energy donor and an acceptor are adjacent to each other, the closer they are, the more energy transfer efficiency increases, and the fluorescence intensity of the acceptor fluorescent substance increases and the fluorescence intensity of the donor fluorescent substance decreases. By measuring changes in fluorescence intensity, instantaneous changes in distance in nanometers (nm) can be distinguished.
When observing a single fluorescent substance, a total internal reflection fluorescence microscope is used. Total reflection fluorescence microscopy selectively illuminates fluorescent substances with an evanescent wave generated by incident light at an incident angle greater than a certain critical angle. Background fluorescence can be minimized and high-resolution images can be obtained, enabling high-resolution analysis that cannot be performed with a general fluorescence microscope, making it suitable for observing nucleic acid-protein or protein-protein interactions. This single-molecule fluorescence imaging explores the mechanisms that regulate gene expression by imaging how nucleic acid-protein complexes form and function in real time.
In detail, we are studying nucleic acid structural changes, nucleic acid-protein interactions, and protein conformational changes. By labeling nucleic acids and enzyme proteins with a fluorescent substance, changes in the distance between molecules can be detected as they interact. Using the same principle, a single nucleic acid molecule or protein molecule can be labeled with multiple fluorescent substances to identify changes in the shape or structure of the target molecule. Phagocytosis plays an important role in immune response and removal of cancer cells and apoptotic cells. Our lab studies the effects of mechanical stimulation and the activation mechanism on the activation of adhesion G protein-coupled receptors involved in cellular functions such as phagocytosis. Using single-molecule force spectroscopy techniques, such as magnetic tweezers, we observe the effects of mechanical force on receptor proteins on a molecule-by-molecule basis. Magnetic tweezers pull magnetic beads using magnetic force, allowing the effect of attraction on nucleic acids or proteins connected to the beads to be observed. We are also conducting synthetic biology research to create new substances to promote the removal of cancer cells by macrophages. Chimeric antigen receptor T cells used in conventional cancer immunotherapy have the disadvantage of not being able to deeply penetrate tumor tissue. By regulating the interaction between macrophages and cancer cells, which are highly permeable to tumor tissue, we aim to induce macrophages to recognize cancer cell-specific substances and remove them through phagocytosis. To adjust intercellular ligand-receptor interactions, we are designing and synthesizing chimeric receptors that link two types of receptors and connecting materials that physically connect cancer cells and macrophages.
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