• To properly understand the functions of biomolecules, it is essential to observe them under physiological conditions where the interactions with other biomolecules are preserved. Therefore, we are developing new functional molecules using both organic chemistry and protein science approaches, and working on the visualization and optical control of biomolecules and their functions. Especially, we have developed fluorescent probes that quantitate the concentration of biomolecules or ions in subcellular regions such as organelles and caged compounds and photoswitches that optically manipulate the biomolecular functions.

By applying nanoscale surface modification to individually designed 3D-printed titanium implants based on CT data, a biomimetic microenvironment is recreated, enabling regeneration of periodontal ligament-like tissue through host stem cell induction. This provides a novel treatment approach without cell transplantation for cases where existing implants are difficult to adapt.

Conventional implant treatment assumes direct bonding with bone, thus disregarding the regeneration of periodontal tissues such as the periodontal ligament. Furthermore, some patients avoid treatment due to concerns about bone-cutting surgery and multiple invasive procedures. This technology utilizes a nano-surface to induce stem cells, forming periodontal tissues similar to natural teeth. This enables the restoration of natural occlusal sensation through a single minimally invasive procedure.

• Custom-designed for each patient's root morphology, it reproduces natural force transmission and chewing sensation. Furthermore, by utilizing nanostructures to control cell adhesion and differentiation, it enables periodontal tissue reconstruction without the need for cell transplantation or regenerative factor administration.

In the future, we aim to collaborate with implant manufacturers to advance mass-production prototyping and quality evaluation, targeting practical application as a medical device. We also seek partnerships with companies and management talent who can jointly undertake strategic planning and clinical deployment for commercialization.

• Pattern recognition receptor (PRR) family plays an important role in the defense through recognition of pathogen-associated molecular patterns or microorganisms-associated molecular patterns (PAMPs/MAMPs).
• Some functional feed materials are thought to regulate intestinal immunity by contact and stimulation of epithelial cells and immunocompetent cells via PRRs in the gastrointestinal tract and induction of cytokine production. In this "new world" of feed immunology, however, much remains unknown about the underlying mechanisms of intestinal immunity because of lack of appropriate intestinal immunoassay system for livestock animals.
• We have advanced application of originally established porcine and bovine intestinal epitheliocytes (PIE, BIE) cell lines (see photo) for evaluation of immunobiotics and immunogenics exerting anti-inflammatory responses both in PIE cell monolayer and co-culture system with porcine peyer's patch immune cells as a peyer's patch culture model (see illustration).

This evaluation system may also contribute to elucidate immunoregulatory mechanism of immunobiotics and immunogenics mediated by pattern recognition receptors essential to future development of not only immunobiotic feeds but also vaccines using immunobiotics to prevent specific diseases. This can benefit mankind by offering immunobiotic feeds as a safer alternative to conventional antibiotic drug therapy.

• Pattern recognition receptor (PRR) family plays an important role in the defense through recognition of pathogen-associated molecular patterns or microorganisms-associated molecular patterns (PAMPs/MAMPs).
• Some functional feed materials are thought to regulate intestinal immunity by contact and stimulation of epithelial cells and immunocompetent cells via PRRs in the gastrointestinal tract and induction of cytokine production. In this "new world" of feed immunology, however, much remains unknown about the underlying mechanisms of intestinal immunity because of lack of appropriate intestinal immunoassay system for livestock animals.
• We have advanced application of originally established porcine and bovine intestinal epitheliocytes (PIE, BIE) cell lines (see photo) for evaluation of immunobiotics and immunogenics exerting anti-inflammatory responses both in PIE cell monolayer and co-culture system with porcine peyer's patch immune cells as a peyer's patch culture model (see illustration).

This evaluation system may also contribute to elucidate immunoregulatory mechanism of immunobiotics and immunogenics mediated by pattern recognition receptors essential to future development of not only immunobiotic feeds but also vaccines using immunobiotics to prevent specific diseases. This can benefit mankind by offering immunobiotic feeds as a safer alternative to conventional antibiotic drug therapy.

• Pattern recognition receptor (PRR) family plays an important role in the defense through recognition of pathogen-associated molecular patterns or microorganisms-associated molecular patterns (PAMPs/MAMPs).
• Some functional feed materials are thought to regulate intestinal immunity by contact and stimulation of epithelial cells and immunocompetent cells via PRRs in the gastrointestinal tract and induction of cytokine production. In this "new world" of feed immunology, however, much remains unknown about the underlying mechanisms of intestinal immunity because of lack of appropriate intestinal immunoassay system for livestock animals.
• We have advanced application of originally established porcine and bovine intestinal epitheliocytes (PIE, BIE) cell lines (see photo) for evaluation of immunobiotics and immunogenics exerting anti-inflammatory responses both in PIE cell monolayer and co-culture system with porcine peyer's patch immune cells as a peyer's patch culture model (see illustration).

This evaluation system may also contribute to elucidate immunoregulatory mechanism of immunobiotics and immunogenics mediated by pattern recognition receptors essential to future development of not only immunobiotic feeds but also vaccines using immunobiotics to prevent specific diseases. This can benefit mankind by offering immunobiotic feeds as a safer alternative to conventional antibiotic drug therapy.

By applying nanoscale surface modification to individually designed 3D-printed titanium implants based on CT data, a biomimetic microenvironment is recreated, enabling regeneration of periodontal ligament-like tissue through host stem cell induction. This provides a novel treatment approach without cell transplantation for cases where existing implants are difficult to adapt.

Conventional implant treatment assumes direct bonding with bone, thus disregarding the regeneration of periodontal tissues such as the periodontal ligament. Furthermore, some patients avoid treatment due to concerns about bone-cutting surgery and multiple invasive procedures. This technology utilizes a nano-surface to induce stem cells, forming periodontal tissues similar to natural teeth. This enables the restoration of natural occlusal sensation through a single minimally invasive procedure.

• Custom-designed for each patient's root morphology, it reproduces natural force transmission and chewing sensation. Furthermore, by utilizing nanostructures to control cell adhesion and differentiation, it enables periodontal tissue reconstruction without the need for cell transplantation or regenerative factor administration.

In the future, we aim to collaborate with implant manufacturers to advance mass-production prototyping and quality evaluation, targeting practical application as a medical device. We also seek partnerships with companies and management talent who can jointly undertake strategic planning and clinical deployment for commercialization.

The recent spate of extreme weather events is threatening to reduce crop seed and fruit production. We have identified a catalog of genes that respond under low and high temperature stress, and will construct a system that enables production under temperature stress through genome editing and other methods.

In addition to conventionally used genetic recombination methods, genome editing technology has made it possible to modify genes that can be used for practical purposes.

• Crops are important for food, environment recovery, energy production, and amenity activity for human being. For improvement of crop seed production, the breeding of crops having environmental stress, is important. Especially the developmental stage from pollination to fertilization is quite weak for these environmental stresses. Thus, by breeding of reproductive trait, we will establish the high productivity and quality of crop seeds. From our research, we found several stress-tolerant genes. We already started the research by both basic and applied level.

For application, we evaluated by taking prize for application in 2001. And our basic data has been published in international Journal, "Nature" and "Science". If anyone is interested in these genes, we hope to conduct to collaborative research for establishing the useful breeding lines.

Cells comprising biological tissues are surrounded by a structure known as the stroma, and their behavioradapts in response to stimuli generated by flow and transport phenomena. Despite its importance, ourunderstanding of how cells respond to their surrounding microenvironment remains limited, hindering thedevelopment of effective disease prevention and treatment strategies. A significant challenge has been thedifficulty in observing cellular behavior while simultaneously controlling the local culture environment.Although microfluidic devices have become increasingly prevalent in recent years, they have not fullyaddressed the need for comprehensive environmental control. To overcome this limitation, we developed the"stromal function chip," which focuses on three critical environmental factors within the stroma: oxygenconcentration, pH, and interstitial flow. This innovative platform enables precise and rapid manipulation ofthese parameters while facilitating real-time observation of both individual cellular responses and complexcell-cell interactions.

Traditionally, stage incubators mounted on microscopes have been employed to maintain culture conditionsduring time-lapse observations of cellular behavior. However, these conventional systems present significantlimitations in actively and rapidly controlling localized changes within the culture microenvironment. Whilerecent advances in microfluidic devices and organ-on-a-chip technologies have enhanced our ability toobserve cellular responses under controlled conditions, these approaches still exhibit considerable constraintsin achieving comprehensive environmental regulation. In contrast, our newly developed chip providesprecise, dynamic, and immediate control over the culture microenvironment during cellular experiments,enabling high-fidelity visualization and quantification of complex cellular dynamics in response to environmental stimuli.

• The stromal function chip features sophisticated architecture comprising cell culture channels with multiplegas channels strategically positioned in vertical alignment above them. Through the controlled delivery ofprecisely mixed gases containing specific oxygen and carbon dioxide concentrations to these gas channels,the chip facilitates gas exchange that enables exquisite regulation of both oxygen concentration and pHwithin the cell culture microenvironment. This approach represents a significant advancement overconventional chemical reaction-based methods, as it eliminates potential cellular toxicity while providinghighly flexible and dynamic control over oxygen concentration and pH. Furthermore, the chip's innovativedesign allows for the precise modulation of interstitial flow—achieved by embedding hydrogel within theculture channels and establishing controlled hydrostatic pressure gradients between inlet and outlet ports. Bysimultaneously manipulating these three critical environmental factors—oxygen concentration, pH, andinterstitial flow—researchers can systematically investigate cellular response mechanisms and characterizehow cells adapt to specific stromal microenvironmental conditions, thereby advancing our understanding oftissue physiology and pathophysiology.

By precisely recapitulating the hypoxic and acidic microenvironmental conditions that characterize tumorniches and inflammatory sites, this innovative chip serves as a powerful platform for pre-clinical evaluationof therapeutic efficacy, enabling researchers to determine optimal drug candidates and dosage regimens priorto in vivo studies. Moreover, the system serves as a platform/tool for fundamental medical and biologicalinvestigations, allowing for high-resolution cellular observation and analysis under rigorously controlled andphysiologically relevant culture conditions.