OIST-KEIO SHOWCASE TALK Series 7- Science meets Society: Frontiers in Interdisciplinary Approaches to Life Sciences

Tool embodiment is known as the phenomenon that one feels an external object as incorporated into one's body schema during or after using it. While many studies have focused on the perceptual aspects of embodiment, the motor aspects of embodiment have been less explored. This talk will present our studies showing kinematic and perceptual changes induced by tool use practice, which may provide a clue to the psychological mechanisms underlying embodiment.

Hepatocytes are essential for metabolizing substances and can regenerate rapidly without specialized stem cells, depending on the coordinated exchange of gene regulation within metabolic pathways and tissue regeneration. Earlier in vitro hepatocyte models focused either on proliferation or functionality, which often led to a compromise in one of these areas. We created human hepatocyte organoids (HHOs) that effectively combine both proliferation and functionality. In HHO culture, STAT3 activity induced by OSM suppresses the cholangiocyte phenotype driven by YAP activity, thus maintaining hepatocyte identity. The improved functionality of HHOs is expected to enhance our understanding of the fundamental systems that allow hepatocytes to carry out their various functions. 

I have been developing neurorehabilitation treatment methods based on brain plasticity induction techniques and will review the development of motor paralysis treatment methods using the Brain Machine Interface. The development of upper limb rehabilitation using functional electrical stimulation and examples of “treatment pipelines” in which multiple treatment techniques are appropriately linked will also be presented. The Neuromodulation Center, a new initiative at Keio Hospital, will also be introduced as a practical approach to the treatment of severe motor paralysis.

Molecular interaction among the cells and organs transduces and integrates the signals to maintain the health of human body. The structural information is important to understand the molecular mechanism and to make the rational design of the modulators. We have developed the structure-guided synthetic protein to control the synaptic connections in the central nervous system and demonstrated the successful application to the disease model animals such as Alzheimer’s disease and spinal cord injury. To extend this research toward other organs including gut microbiota, we are going to apply structural analysis in the native environment to understand and control multi-organ network.

Recent interactions between neuroscience and AI reveal mutual benefits. Here, we explore behaviors and neural representations in both biologically and artificially intelligent systems across a variety of behavioral paradigms. By training both mice and artificial deep reinforcement learning (RL) agents on the same tasks and analyzing the resulting task representations in their respective neural networks, we found that learning in the mouse cortex exhibits key features similar to those of deep RL algorithms. Our interdisciplinary methodology may define new research trajectories for neuroscience and AI, deepening our understanding of the brain while enhancing machine intelligence through neuroscience-inspired algorithms.

After fertilization, unified parental chromosomes must be accurately duplicated and segregated to all blastomeres to maintain genomic information during embryogenesis. However, how chromosomes are accurately segregated in large vertebrate embryos remain poorly understood, compared to small somatic cell models. Recently, we have established live functional assay systems in medaka (Oryzias latipes) embryos by combining high-quality live imaging with CRISPR/Cas9-mediated genome editing and an auxin-inducible degron 2 (AID2)-based protein knockdown system (Kiyomitsu et al., Nature Communications 2024). In this talk, I will present our recent findings showing unique and unexpected features of early embryonic division. 

Two-photon microscopy in combination with fluorescent sensors allow 3D reconstruction of neurons and imaging of neuronal activity in awake animals. The activity can be imaged from cellular compartments as well as from large populations of neurons. Interestingly, two-photon microscopy can be combined with behavioral experiments.  In my talk, I will present the basics of two-photon microscopy and give several examples of calcium and voltage imaging in cerebellar and cerebral cortex of behaving mice.

Exponential growth is a crucial feature of living systems, that sets them apart from inanimate physical systems. In my talk, I will show how to use exponential growth of cell colonies to study how these organisms replicate their genomes. I will then use a similar approach to relate the speed of epidemic spreading with features of human social structures.

Centrosomes are membraneless cell organelles composed of centrioles surrounded by a pericentriolar material (PCM) matrix. During mitosis, centrioles organize the PCM to recruit microtubule-nucleating factors essential for spindle assembly. In differentiated cells, centrioles serve as templates for cilia and flagella formation. Defects in centrosome assembly are implicated in cancer and developmental disorders. Employing gene engineering and live-cell imaging in the C. elegans system, combined with biochemical reconstitution of macromolecular complexes, we demonstrate that a phosphorylation-dependent conformational change in a PCM matrix protein is essential for centrosome activation during mitosis. Our results highlight a conserved mechanism that ensures mitotic fidelity.   

Photosynthetic organisms rely on protein antennas to capture sunlight and transfer energy to photosynthetic complexes for chemical conversion. However, 95-99% of the captured energy is lost as heat, limiting efficiency. It is estimated that solar energy captured by protein antennas could be enhanced by up to 200%. Phycobiliproteins, a type of antenna protein, offer promising solutions due to their unique spectral absorption and adaptability. By engineering these soluble antennas through mutagenesis and chromophore modifications, their absorption spectra can be expanded, enabling more efficient light harvesting across diverse wavelengths. Unlike larger, membrane-bound systems, these mini antennas are ideal for creating customizable energy harvesting systems, optimizing solar energy capture, enhancing biofuel production, and enabling self-sufficient bioelectronic devices.