Hokkaido University Research Profiles

Japanese

3. Good Health and Well-being: 48

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  • 1. No Poverty
  • 2. Zero Hunger
  • 3. Good Health and Well-being
  • 4. Quality Education
  • 5. Gender Equality
  • 6. Clean Water and Sanitation
  • 7. Affordable and Clean Energy
  • 8. Decent Work and Economic Growth
  • 9. Industry, Innovation and Infrastructure
  • 10. Reduced Inequality
  • 11. Sustainable Cities and Communities
  • 12. Responsible Consumption and Production
  • 13. Climate Action
  • 14. Life Below Water
  • 15. Life on Land
  • 16. Peace and Justice Strong Institutions
  • 17. Partnerships to achieve the Goal
  • A Novel Porous Structure with High Mechanical Performance for Additive Manufacturing

    Biomimetic design based on bone biomechanics

    A novel three-dimensional (3D) printed porous structure with high mechanical performance is designed biomimetically based on the insights of bone biomechanics. The resulting structure might be lightweight and mechanically isotropic with suppressed fracture progression and high energy absorption.

    Research

    In general, porous structures with repeating units, such as diamond lattices, suffer from mechanical issues, such as fracture development, low energy absorption, and mechanical anisotropy due to these repeating units. To address these issues, we develop a novel porous structure with high mechanical performance for additive manufacturing. The structure is designed biomimetically based on the insights of bone biomechanics. It has a framework made up of 3D isotropically interconnected beams. Here, the beam lengths and bifurcation counts are arbitrarily determined using probability distributions without any repeated units. Furthermore, the structure can be manufactured through the powder bed fusion of a laser beam using metal powders and material extrusion using plastic filaments. Additionally, compression tests revealed that the structure exhibited suppressed fracture progress after the initial fracture and increased energy absorption. Moreover, the fracture behavior of the structure was found to be independent of the compression direction because of its structural isotropy.

    Satoshi Yamada Assistant Professor
    PhD
    Division of Mechanical and Aerospace Engineering, Faculty of Engineering
  • Metabolism of Biological Components and Pre-symptomatic Disorder

    Elucidation of the mechanism of non-infectious pathogenesis by considering the metabolism of biological components: Application as a system of evaluating the functionality of foods

    Based on the metabolic analysis of biological components (bile acids, minerals, etc.), we conduct research on the elucidation of the pathogenesis of various diseases and the establishment of pre-symptomatic disorder models using laboratory animals. We aim to elucidate the point of action in prevention of disease onset via dietary intervention.

    Research

    The composition of bile acids synthesized by the liver fluctuates with aging and excessive energy intake, and that can be estimated under these conditions. Therefore, by feeding a very small amount of a specific bile acids to experimental animals, it is possible to create a state that mimics the bile acid environment in the corresponding situation. We have found that this results in fatty liver and related pathologies. We also found that a mild deficiency of zinc is a pre-symptomatic disorder model for ulcerative colitis. These findings indicate that minor metabolic changes that occur continuously due to dietary bias (excess or deficiency) are involved in the onset of infectious and non-infectious diseases, and that the experimental system itself, which mimics the situation by controlling dietary components, can serve as a model of pre-symptomatic disorders. Currently, we are constructing various pre-symptomatic disorder models and analyze their pathogenic mechanisms. We are also using these systems to evaluate the functionality of foods.

  • A New Model of Aging by Decreased Protein Metabolism

    Aging causes a variety of metabolic changes. A physical condition of so-called “decreased metabolism” increases the risk of aging, lifestyle-related diseases, and aging-related disorders. We have developed a mouse model that demonstrates aging due to decreased protein metabolism.

    Research

    Proteasomes, which are responsible for the degradation of intracellular proteins, are expressed in cells across species and are important for the maintenance of biological functions. Proteasome activity is decreased in older individuals, and the aging-related loss of proteasome function is involved in the development of aging and aging-related diseases. With this study, we created a mouse model in which proteasome activity is decreased and aging occurs. When this model is exposed to a high-fat diet, fatty liver is exacerbated, and when exposed to tobacco smoke, pulmonary diseases occur. By applying this model, we can elucidate the protein abnormalities and target molecules that cause various human diseases.

  • A Single Microscopic Image Can Tell the Whole Story

    A Single Microscopic Image Can Tell the Whole Story

    The Nikon Imaging Center was established as a facility where researchers throughout Japan can use the latest biological microscopes, and is now operated by the Research Institute for Electronic Science. Our dedicated staff will explain how to operate the equipment and software to beginners who may never have touched a microscope before.

    Research

    Recent years have seen an increasing demand for bioimaging and significant performance improvement in gene transfer technology, molecular and cellular marking technology using fluorescent proteins and observation equipment such as microscopes. However, high performance microscope systems are very expensive, and it is difficult to obtain all the necessary equipment, especially at the start. Another factor that makes imaging technology difficult is the fact that not everyone can easily obtain excellent data
    The center’s equipment is made available for researchers outside the university and we not only provide instructions on the operation of the equipment and software, but also technical know-how on imaging. We have also joined the Advanced Bioimaging Support (ABiS) platform from this year, and are involved in supporting the use of cutting-edge microscopes in collaboration with other microscope facilities in Japan. We’d like companies that are exploring the application of imaging to consider the use of our services.

  • Accelerometer to Identify Where You Stumble

    To prevent falls in elderly people

    To avoid serious injuries due to falls, we studied a system that can search places with a potential danger of stumbling, which is a sign of a fall, based on people’s daily activities. The system uses an accelerometer embedded in sandals to identify the stumbling point, and an infrared sensor network on the ceiling to identify the location of the stumbling point.

    Research

    According to a survey by the Tokyo Fire Department in 2014, approximately 80% of all cases of emergency transportation of elderly people are due to accidents involving falls. Since their consciousness cannot keep up with their declining physical abilities, they stumble over small steps, footwear, or clothing. Much research is done on the detection of falls, but it is too late after the actual fall. Therefore, we decided to eliminate the causes of falls by detecting the areas where people often stumble. Wearable devices have problems with forgetfulness and psychological resistance to wearing it, while non-wearable devices such as surveillance cameras have problems with blind spots and privacy protection. In this study, an acceleration sensor is attached to normal sandals to detect a stumble, while a network of infrared sensors installed on the ceiling works in conjunction to identify the location of the stumble. In our experiments, we were able to distinguish falls easily, but the accuracy rate of distinguishing stumbling from normal walking is currently only about 1/4, so we hope to improve the accuracy in the future.

  • Alpha-defensins Prompting a Paradigm Shift in the Intestinal Environment

    From a scientific understanding of ishoku-dougen (an idea that the same principles underlie a normal diet and medical treatment) to preventive medicine

    The α-defensins secreted by Paneth cells regulate the intestinal microflora and are deeply involved in their elimination and symbiosis. We will evaluate the intestinal environment from the viewpoint that the intestinal environment is defined by the three elements of food, α-defensins and intestinal bacteria, and create a paradigm shift to contribute to the clarification of disease mechanisms and the development of preventive medicine.

    Research

    Using isolated small intestinal crypts and enteroids, which are three-dimensional small intestinal epithelial culture systems, we will elucidate the innate immunity of Paneth cells, which are intestinal epithelial cells (that secreteα-defensins), symbiosis with intestinal bacteria, regeneration and differentiation and other molecular mechanisms associated with various functions, taking advantage of state-of-the-art analytical methods such as confocal laser microscopy and flow cytometry. The intestine forms a network between various organs in the body and by analyzing the mechanism of the intestinal environment focused on the function of Paneth cells will make it possible to control the intestinal environment and create preventive measures and treatments for various diseases. From the perspective of the intestines, “food” and “drugs” virtually mean the same thing. We hope to contribute to the realization of a healthy longevity society through industry-academia-community collaboration based on the knowledge we have created.

  • An Idea-supporting Multimedia Search System

    An information retrieval system that organically links images, video and other data to help searchers find inspiration and ideas.

    The idea-supporting multimedia search system organically links unstructured data such as images, music and video, extracts inherent similarities and effectively presents them to searchers to help them find ideas and inspiration.

    Research

    We have succeeded in establishing associations and similarities between different media, and developed an associative search scheme that takes ambiguity of multimedia information into consideration (fused search). We have also realized a new search engine and interface by quickly introducing modeling of personal preferences through user networks and visualization of similarities in preferences through user interfaces (personal adaptive search). Use of the search engine and interface enables a completely new search that effectively utilizes the polysemy and ambiguity inherent in multimedia contents.

  • Application of Adhesive Gels to Intraoral Devices

    Innovation for maintaining intraoral devices with adhesive gel

    Intraoral appliances used in dentistry need to be clasped or otherwise attached to the teeth to remain in place. This research involves the development of prototype intraoral floor appliances (e.g., palatal obturator) that are attached to the skin or mucosal side of a polycarbonate frame using PCDME or other types of adhesive gel.

    Research

    When an intraoral appliance in this study is used as a palatal obturator, it does not require a clasp, unlike conventional palatal obturators (Fig. 1), because the adhesive gel can be fixed by contact with the oral mucosa. As a result, gingivitis caused by the clasp can be reduced; interference with the sideways growth of the row of teeth can be avoided; it can be comfortably worn without a sense of tightness or pressure; and it is safe to put on and take off the palatal obturator without damaging the oral cavity. It can also be worn before the teeth have erupted, allowing language training to begin at an early stage. The gel can also be thinly spread on the thin frame, and a uniform thickness can be obtained. This reduces the sense of discomfort when wearing the product and ensures a larger oral space, which is effective for language training by expanding the area where the tongue can move.

  • Basic Research to Design Healthy Life Rhythms Considering Biological Clocks

    Japanese people sleep less than the global average, and the economic loss due to sleep disorders is estimated to be about 6 trillion yen per year. At our laboratory we specialize in chronobiology, which is the study of the biological clock, which is deeply related to sleep. Our goal is to contribute to the health of the nation by promoting research of chronobiology.

    Research

    The biological clock is an important biological strategy that regulates our behavior (timing of sleep and wakefulness) and our body’s internal environment, so that we can be fully active during the day and get good sleep at night. However, in today's society, many of us are forced to live against our biological clocks due to night shifts, jet lag, 24-hour work schedules, and so on. In order to lead a healthy life throughout our lives, we need to understand the structure and function of our biological clocks, and actively design and optimize our life rhythms according to our life stages and individual lifestyles. At our laboratory, we are studying the mechanism of the effects of light and exercise on the biological clock, the development of effective nutritional dietary guidance methods based on chrono-nutrition, and the relationship between seasonal variations in sleep and biological rhythms and physiological functions.

    Yujiro Yamanaka Associate Professor
    Ph.D. in Medicine
  • Coherent Raman Scattering Endoscope

    Development of an eye for a novel endoscopic surgical support robot using coherent Raman scattering for label-free nerve visualization

    Raman scattering provides insight into molecular species and structures without staining, but its use has been limited due to its extremely weak scattering. We are developing microscopes and endoscopes that provide Raman images in real-time by using coherent Raman scattering phenomena with ultrafast lasers.

    Research

    Raman scattering has been used in chemical analysis, physical chemistry, and semiconductor research because it provides information on molecular species and structures without staining. It is also recently actively applied to the biological and medical fields. However, Raman scattering is very weak. We have developed a multifocal coherent Raman scattering microscope with integrated a wavelength-tunable synchronous picosecond laser and realized imaging at 100 frame/s, which is faster than the video rate. We also demonstrated that nerves are visualized without staining and at high speed under a rigid endoscope of 12 mm in diameter and 550 mm in length. It is expected to be a new imaging tool for nerve-sparing endoscopic surgery.

  • Communication Robot System

    Social space recognition system using dialogue activity and attention guidance system and multiple robots

    By calculating the level of activity of a dialogue between people, a robot can recognize the intensity of that dialogue space and adapt its behavior to the context. Furthermore, by applying this mechanism to the behavior of multiple robots, it will become possible to guide the user's attention.

    Research

    Our dialogue activity calculation system calculates the real-time activity level using information such as the distance between the interactants, voice data, and body movements. By using this activity level, the robot can determine whether it is allowed to enter the dialogue space or interrupt the dialogue, and can take contextually adaptive actions. Furthermore, by having multiple robots act in a way that increases the dialogue activity level for each other's actions, the user's attention (e.g., gaze) can easily be guided. Such a system for generating robot behavior using the level of dialogue activity has not been included in conventional research on social robots, and can be applied to robots at reception desks and home robots for households.

  • Development of a Compact Dosimeter Using an Optical Fiber

    Application of ultra-small dosimeters to radiotherapy and diagnostic fields by combining an ultra-small scintillator and an optical fiber

    In recent years, there has been increasing interest in radiation protection against serious skin damage caused by X-ray fluoroscopy. Through this research, we developed a plain ultra-small plastic scintillator dosimeter that does not show up on X-ray fluoroscopic images attached to the end of the optical fiber to prevent late-onset radiation injury.

    Research

    For endovascular treatment with X-ray fluoroscopy (IVR; Interventional Radiology), the patient is subjected to prolonged X-ray fluoroscopy. Repeated procedures for myocardial infarction and other conditions may cause ulcers and other serious skin disorders. Conventional dosimeters have the problem that they cause a shadow in the fluoroscopy detection area. In particular, since energy dependence affects the accuracy of measurements, there have been no dosimeters that are compact, have little energy dependence, and do not cause shadows on fluoroscopy. However, the SOF dosimeter developed in this study is characterized by not showing up under X-ray fluoroscopy because the density of the sensor part is close to that of the living body. At present, the SOF dosimeter has achieved sensitivity variation of 5% or less in a range of 60 to 150 kV, and we are working with a company to improve the sensor material to further reduce the sensitivity variation.

  • Development of a Method to Prevent Post-Thoracic Surgery Atrial Fibrillation Using Carnitine

    We will conduct a randomized, multicenter study to determine whether perioperative oral carnitine therapy can reduce postoperative atrial fibrillation (POAF) in patients with valvular heart disease. In case of lung and esophageal cancer patients, a single-arm interventional study will be conducted because similar studies have not been conducted before.

    Research

    Postoperative atrial fibrillation (POAF) after thoracic surgery is a frequent problem leading to increased incidences of stroke, heart failure, and infection, and resulting in prolonged hospitalization. Although beta-blockers are the only effective treatment, their efficacy rate is less than 50%, and their side effects often preclude their use. Recently, carnitine preparations, which are fatty acid metabolism ameliorators, have been reported to suppress arrhythmias after myocardial infarction and coronary artery bypass surgery due to their anti-inflammatory and fatty acid metabolism ameliorating effects. As part of this project, we will conduct a randomized, multicenter study to determine whether perioperative carnitine medication can suppress POAF in patients with valvular heart disease. In case of lung cancer and esophageal cancer patients, a single-arm interventional study will be conducted to evaluate the safety and POAF reduction rate, which will be useful for future randomized studies.

  • Development of Gd?Si?O?-based High-performance Scintillators and Their Application

    Development of high luminescence scintillators for radiation detectors

    Scintillators are materials that emit light by radiation and are used in medical diagnostic equipment, and for oil exploration and other purposes. Gd2Si2O7 (GPS) scintillators have excellent features such as high luminescence, high energy resolution and non-tidal dissolution, and can be made into single crystals, ceramic plates and powders.

    Research

    The Gd2Si2O7: Ce (GPS) single crystal scintillator has excellent features such as high luminescence (1.4 times that of NaI:Tl), high energy resolution, non-tidal and no self-radioactivity, and can be used in high temperature environments of 250°C or higher. The technology has been transferred to Oxide Corporation, and is now ready for use in SPECT and other applications. We have also established a stable manufacturing technology for 5 cm square GPS sintered plates. By combining a position sensitive photomultiplier tube, it is now possible to detect nuclear fuel materials emitting alpha rays, which were released in the Fukushima Daiichi Nuclear Power Plant accident, with high sensitivity. The prototype device succeeded in detecting nuclear fuel-induced α-ray-emitting radionuclides in an environment with nuclear fuel-induced α-ray-emitting radionuclides: natural radioactivity (radon progeny) = 1:200, which had been inconceivable with conventional devices.

  • Development of Mathematical Algorithms for Biomedical Optical Imaging

    Development of a mathematical model for light propagation model inside biological tissues

    A highly accurate and computationally efficient light propagation model is necessary for the progress of biomedical optical imaging. In this study, we have succeeded in constructing a fast solution method for the radiative transfer equation that describes light propagation with high accuracy. We are working on the advancement of an optical diagnosis and treatment using the proposed method.

    Research

    In this study, we are constructing a mathematical algorithm for biomedical optical imaging based on the radiative transfer equation. Our goal is to develop an imaging technique with excellent image resolution that can be applied to biological tissues and body parts where conventional imaging based on mathematical models cannot be applied. Until now, the numerical computational burden of the radiative transfer equation has been enormous, limiting its applicability to small-sized organisms. In this study, we have succeeded in developing a highly accurate and computationally efficient light propagation model by coupling the radiative transfer equation and the photon diffusion equation. Optical imaging based on the developed light propagation model can be applied to various biological tissues and sites. Currently, we are working on applying the model to the optical diagnosis of thyroid tumors in the human neck and the in-vivo evaluation of optical property values in biological tissues.

  • Development of novel control strategies for intractable diseases in animals

    Development of immunotherapy using antibody drugs and protein preparations for chronic infectious diseases and tumors in domestic and companion animals

    In case of intractable diseases, the elimination mechanisms of pathogens and tumors are disturbed in vivo. This is thought to be due to various immunosuppressive factors that exhaust immune cells. the mechanism of eliminating pathogens and tumors in the body is disturbed, probably due to various immunosuppressive factors that exhaust immune cells. This study is aimed to develop novel formulations that target the immune evasion mechanism and apply them as a novel treatment for animal diseases.

    Research

    Research objective: Development of veterinary antibody drugs and protein drugs targeting PD-1 and other immunosuppressive factors and their application to therapeutics. Comparison with and advantage over conventional technology: This approach does not target a specific disease, but rather a wide range of diseases in which the anti-pathogen and anti-tumor effects are lost due to immunosuppressive mechanisms. Since the immunotherapy is based on activated lymphocytes, it is expected to have a multifunctional immune-enhancing effect. Uniqueness of the research: There are limited reports of clinical applications of this approach in the veterinary fields. Characteristics: We will establish therapeutic antibodies for animals and evaluate their effectiveness against various diseases. Efficacy: We aim to provide new treatments for diseases of livestock (cattle, horses, pigs, etc.) and companion animals (dogs, cats, etc.) for which there are no effective vaccines or treatments.

  • Development of Novel Inhibitors Targeting the Receptor-Bound Prorenin System

    Development of drugs that inhibit (pro)renin receptors involved in pathogenesis such as chronic inflammation and angiogenesis

    We are working to elucidate the involvement of the renin-angiotensin system (RAS) in the pathogenesis of diabetic retinopathy and other retinal choroidal diseases, and to develop inhibitors of the (pro)renin receptor, which is upstream of the RAS, and to conduct basic research from a broad perspective.

    Research

    Age-related macular degeneration and diabetic retinopathy are retinal and choroidal disorders that major causes of blindness and are regarded as chronic inflammatory disorders associated with lifestyle-related diseases. However, we have yet to develop a fundamental treatment or elucidate the pathogenesis of these disorders. We have previously reported that the receptor-associated prorenin system (RAPS) regulates the molecular pathogenesis of disorders upstream of inflammation and angiogenesis in organ damage in lifestyle-related diseases. We are currently conducting basic research targeting the (pro)renin receptor, which is at the center of the receptor-associated prorenin system, with a view to drug discovery using technologies such as comprehensive small molecule compound screening and drug molecular design methods. Using animal models of diseases, we are also attempting to elucidate the function of (pro)renin receptors and to establish therapeutic strategies for early intervention in disease states while minimizing the impact on the physiological functions.

  • Development of Reagents for Highly Efficient Transfection of siRNA into Immune Cells and Their Application to Cancer Immunotherapy

    Development of next-generation drug delivery systems

    We have developed a reagent (YSK12-MEND) to introduce siRNA into immune cells with high efficiency. If siRNA is introduced into immune cells using this reagent, the expression of immunosuppressive genes can be reduced with high efficiency, and thus it is expected to be applied to cancer immunotherapy using immune functions.

    Research

    We have developed YSK12-MEND, a reagent that can efficiently transfect siRNA, a gene expression inhibitor, into mouse and human immune cells. By using the novel reagent, the efficiency of siRNA transfection into mouse dendritic cells has improved more than 10-fold compared to the commercial product (Lipofectamine RNAiMAX). It is known that the function of immune cells is suppressed by cancer cells in cancer patients, although humans have an immune function to fight cancer cells. siRNA delivery using YSK12-MEND can efficiently suppress the expression of immunosuppressive genes in immune cells, which will enable humans to fight cancer cells with their own immune function. YSK12-MEND is expected to be one of the promising candidates for this purpose.

  • Development of Therapeutic Agents and Biomarkers for Stress-induced Diseases

    Molecular psychoneuroimmunology to understand the molecular mechanism of “disease starts in the mind”

    Chronic stress has become a widespread problem in our society as it may lead to sudden death or other serious problems due to overwork or insomnia. We have clarified the molecular mechanism by which chronic stress induces organ damage and sudden death in mice through the activation of specific neural circuits. This system can be used to search for therapeutic targets for stress-induced diseases.

    Research

    We are studying the link between stress and disease. Recently, when autoreactive T cells against central nervous system antigens were transferred to mice that had been subjected to chronic stress, the mice suddenly died. The cause of death was heart failure due to hemorrhage in the stomach and duodenum, as found with humans. Stress-specific activation of neural circuits induced microinflammation in the brain, where transferred T cells, etc. were accumulated in specific blood vessels, and a new neural circuit activated by this triggered the gastrointestinal disorder and heart failure. There have been no animal model of stress in which the molecular mechanism has been elucidated, and this model is useful for screening of new drugs for stress-induced diseases. Using this system, we also identified a group of molecules of which the expression is upregulated in specific blood vessels in the brain during stress, and antibodies against these molecules suppressed sudden death. We are also currently identifying marker candidates for autoreactive T cells in humans.

  • Discovery and Application of a Novel Enzyme Capping the N-Terminus of Peptides

    Novel peptide ligase

    ・We discovered a novel enzyme catalyzing the attachment of non-proteinogenic amino acids to the amino termini of various peptides.
    ・It is expected to lead to the protection of useful bioactive peptides and the development of new anti-tuberculosis drugs.

    Research

    One of the disadvantages of using peptides as pharmaceuticals is that they are degraded by peptidases. Since exo-type peptidases acting on peptide termini are mostly responsible for degradation in humans, attachments of non-proteinogenic amino acids to the peptide termini is valuable from the viewpoint of protecting them from degrading enzymes for drug development. In this study, as a result of biosynthetic studies of the peptide antibiotic pheganomycin, we found an enzyme that capped the amino terminus of various peptides consisting of 2 to 18 amino acids with a phenylglycine derivative, which is a non-proteinogenic amino acids. To understand the broad substrate specificity, we solved the crystal structure of the enzyme and found that the enzyme has a large substrate binding site, which is not found with other enzymes, and that can thus accept a variety of substrates. Nat. Chem. Biol., 11, 71 (2015).

  • Electrochemically Responsive Organic Dyes

    From electrochromism to multiple responses (fluorescence, circularity)

    Based on cationic organic dyes, which allow easy control of color tone, we offer a group of materials that can respond in multiple ways, including fluorescence and optical rotation (circular dichroism). This technology is designed to suppress the decomposition process of reduced species, and the bi-stability of oxidized and reduced species is such that exchange does not occur, even when they are mixed.

    Research

    Electrochromism is a general term for compounds that change their color tone in response to changes in external electrical potential. As materials that can undergo reversible color changes, they are attracting attention as light control materials for smart windows and display functions for electronic paper. Materials of which not only the color tone, but also fluorescence, optical rotation (circular dichroism), etc. can be changed, enable tailor-made responses according to the application.
    With this technology, we provide a group of substances with multiple responses based on cationic organic dyes of which the color tone can easily be controlled. The reduced species of cationic dyes are generally reactive, and the repeatability of the response is low, but with this technology, the decomposition process of the reduced species is suppressed by incorporating two cationic moieties. The bi-stability of the oxidized and reduced species, in which no exchanges occur, even when they are mixed, makes it possible to apply this technology to high-density recording materials.

  • Elucidation and Application of New Functions of Food by Evaluating the Intestinal Environment

    Development of a new intestinal environment evaluation system for food and medicine

    Food materials and ingredients, intestinal bacteria acting as parasites, and host Paneth cell α-defensins are the three elements that determine the “intestinal environment.” We are developing an intestinal environment evaluation system based on the new paradigm that crosstalk between these three elements affects health maintenance and disease to elucidate food functionality and apply it to disease prevention.

    Research

    In our original definition of “intestinal environment,” three elements, namely, food materials and ingredients, intestinal bacteria acting as parasites, and host Paneth cells α-defensin, determine the “intestinal environment,” and their crosstalk affects health maintenance and disease. This definition has prompted a paradigm shift in food functionality. The purpose of this study is to clarify the involvement of α-defensins in health maintenance, disease development and pathogenesis. This will help us establish a novel functional evaluation system of food and international criteria to evaluate the intestinal environment. By combining a tissue culture system with an α-defensin quantification system, we will lay the foundation for systematic analysis of the relationship between various intestinal functions and food functions of which the mechanisms are still unknown. This will be the first to elucidate immunostimulation and the control of aging substances by digested food materials and ingredients and drugs. We aim to obtain new scientific indicators to create high added value for food.

  • Elucidation of Nutrient Sensing Mechanisms in the Digestive Tract

    Regulation of blood glucose by food peptides through their effects on the enteroendocrine system

    Hormones secreted by endocrine cells that sense nutrients in the gastrointestinal tract regulate various physiological responses immediately after eating. In the course of studying this mechanism, we found through animal studies that food peptides can promote the secretion of the gastrointestinal hormone GLP-1 and reduce the elevation of plasma glucose levels.

    Research

    Various gastrointestinal hormones released by enteroendocrine cells that sense nutrients in the digestive tract, play an important role in regulating various physiological responses after meals. We have focused on the gastrointestinal hormone GLP-1, which is known as an anti-diabetic hormone, and found a food peptide (derived from corn) that strongly promotes the secretion of GLP-1. By orally administering this peptide to rats, we found that GLP-1 secretion was promoted and plasma glucose elevation was suppressed. Our research is aimed to elucidate how this peptide is recognized by enteroendocrine cells, and to control postprandial plasma glucose levels and appetite by controlling the secretion of gastrointestinal hormones with various food components.

  • From Landscape to Hometown Revitalization

    Creating community value through resident participation

    From the perspective of landscape planning, we are researching ways to preserve and utilize the local environment by linking it to people's awareness and social understanding. In recent years, we have been practically researching how values and spatial needs that change with society, such as “health” and “funerals” can be reflected in the landscape.

    Research

    To conserve and manage local resources through resident participation, the “landscape” approach, which views the region from people's perspective, is very effective. We are developing research on people's and society's landscape perception, and conducting empirical research on how to utilize people’s place attachment in local resource management.
    Environmental planning using health resorts (Kurort)
    In Germany, medical insurance covers services at government-recognized recuperation and health resorts that make use of the natural environment such as hot springs, the sea, and the climate. In Japan, too, efforts are underway to create health resorts (Kurort) that combine health tourism with local health promotion.
    Forest utilization as burial sites:
    To utilize forest resources, we are conducting practical research on the development of forest burial sites in Japan, modeled after Germany’s examples. As a new method of managing forests, which account for 70% of Japan’s land area, we are promoting the creation of forest burial sites in various regions as a means of regional management in aging society.

  • Functional Modification of Food Proteins

    Sugar modification for processing and improved health functions

    Using the Maillard reaction to bind sugars to fish meat proteins, we can prepare water-soluble muscle proteins and peptides with modified processing properties and health functions (anti-inflammatory and antioxidant function, suppression of blood pressure increase and suppression of lipid absorption, etc.). It can also be applied to livestock and poultry meat and various proteins.

    Research

    Summary
    The Maillard reaction can be used to bind reducing sugars to proteins and peptides to create new fish food products with modified properties.
    Comparison with conventional technology and uniqueness
    High-molecular complex proteins such as muscle proteins are prone to thermal aggregation, and progression of the Maillard reaction leads to deterioration of various properties. We have developed a new method to create functional materials from unstable proteins such as fish food proteins by controlling both protein denaturation and the Maillard reaction.
    Characteristics of the materials and manufacturing technologies that can be created.
    1. Introduction of sugar chains without using chemical reagents
    2. Making muscle soluble in water and adding highly emulsifiable properties
    3. Improving the stability of unstable proteins
    4. Modification of in vivo active health functions
    5. Can be applied to the development of functional peptides.
    6. No limitations on the form of the raw materials

  • Gel that is Stronger Than Steel

    Soft and tough composite material

    By conjugating glass fiber and self-healing gel, we have achieved a gel that is stronger than carbon fiber-reinforced plastic (CFRP). Since the base material is a gel, it is as flexible as rubber against bending, but tougher than CFRP against tearing, making it difficult to break.

    Research

    The glass fiber composite gel we have developed exhibits unbreakable, untearable and tear-resistant properties. Generally speaking, CFRP and glass fiber reinforced plastic (GFRP) are widely used as composite materials. Similar to these fiber-reinforced plastics, fiber-reinforced gels are hard and resistant to tension because of the characteristics of the fibers, while being soft and flexible on bending because of the characteristics of the gel. The self-healing polyampholyte (PA) gel used as the base material is also strong as such thanks to its ability to dissipate a large amount of energy against deformation. Since the gel is flexible, when it is combined with fiber, local distortions can be transmitted through the fiber to the distant base material, resulting in large energy dissipation of the entire material, meaning that it is remarkably strong.

  • High Strength Gel That Spontaneously Bonds Strongly with Bone Tissue

    Development of a safe, high-strength bonding method between wet materials and bone, which has been difficult to achieve so far, by utilizing bone healing in living organisms

    In answer to the issue of in vivo fixation by applying the much anticipated high-strength hydrogel as a next-generation artificial cartilage or cartilage tissue regeneration scaffold material, we have developed a simple, non-toxic, high-strength adhesion method using hydroxyapatite, an inorganic component of bone tissue.

    Research

    The high-strength, high-toughness double-network gel (DN gel) previously developed by our group has excellent properties such as low wear on cartilage and induction of cartilage tissue regeneration in a natural joint, and is being studied for application as an artificial cartilage material and cartilage regeneration induction material. On the other hand, it is difficult to fix and maintain such a gel in a natural joint, which has been a major issue with the practical use of this material. In this study, we developed a fixation method that allows bone tissue regeneration to progress spontaneously into the gel and adhere firmly by compounding hydroxyapatite (HAp), the main inorganic component of bone tissue, to the surface layer of the DN gel. In addition to excellent mechanical properties and cartilage regeneration ability, the realization of non-toxic in vivo adhesion to bone is a great step forward toward the practical application of DN gel for joint treatment.

  • Hyperpolarized 13C MRI for Genetic Mutation Imaging

    Non-invasive visualization of genetic mutations in tumors by metabolic MRI

    The outcome of cancer treatment largely depends on the type of genetic mutation that the cancer cells carry. Using the characteristic metabolic changes brought about by genetic mutations as an indicator, we are developing a molecular imaging technique to identify mutated genes non-invasively using the latest metabolic MRI.

    Research

    Hyperpolarized 13C nuclear magnetic resonance imaging (MRI) is a state-of-the-art technique for real-time visualization of metabolic reactions in vivo by temporarily amplifying the MRI signal of any compound labeled with 13C tens of thousands of times. It is expected to be a dream molecular imaging technology that can acquire signals from deep inside the body, which is difficult with optical imaging without radiation exposure like PET/CT.
    Cells become cancerous through the accumulation of genetic mutations, and the type of mutation greatly influences the response to cancer therapy. Many cancer-causing mutations are associated with characteristic metabolic changes. Hyperpolarized 13C MRI can be used to non-invasively identify mutated genes in tumors by looking at specific metabolic changes.

  • In Vivo Nucleic Acid Delivery System Based on the Development of Unique Functional Lipids

    Balancing world-class functional delivery of nucleic acids and safety

    We have developed a unique group of functional lipids for the safe and efficient in vivo delivery of siRNA. The lipid nanoparticles containing these lipids showed world-class functional delivery of siRNA in hepatocytes due to their excellent endosomal escape ability and high safety due to their biodegradability.

    Research

    The key to the practical application of siRNA is the development of superior delivery technology, but there is still much room for improvement in the delivery efficiency. In addition, from the viewpoint of practicality, it is also important to secure a wide safe therapeutic window. It is also highly desirable to develop platform technologies that can provide appropriate formulations for different purposes without being limited to specific applications. To achieve these goals, we have developed a unique group of pH-sensitive cationic lipids. We achieved the modulation of acid dissociation constants, which is an important factor for the pharmacokinetics of lipid nanoparticles, enabling a target-specific molecular design. The lipid nanoparticles containing the novel lipid CL4H6 induced gene silencing in hepatocytes with world-class efficiency. No significant hepatotoxicity was also observed even after the administration of approximately 3,000-fold higher dose for 50% gene silencing, thus a high level of safety was confirmed. CL4H6 was rapidly degraded and eliminated after siRNA delivery.

  • Liposomal Bioluminescence Immunoassay

    Preparation of liposomes encapsulating luciferase and application as an ultra-sensitive label in immunoassays

    We have encapsulated the enzyme luciferase (Luc), which catalyzes bioluminescence reactions, in liposome, a lipid bilayer vesicle, and applied it as an ultrasensitive label for immunoassays. As a model substance, we performed immunoassay of C-reactive protein, a marker of inflammation, and found that it could be quantified.

    Research

    Since immunoassay is an essential technology in clinical laboratories and for environmental analysis, technological advances (simplification, high sensitivity, high throughput, etc.) has come essential as the analytes are becoming more diverse and smaller. We aim to construct an ultra-sensitive immunoassay system in which the bioluminescent enzyme Luc is encapsulated in lipid bilayer membrane vesicles, called liposomes, and use it as a label in immunoassays. By encapsulating a large number of Luc in liposomes, it becomes possible to label antibodies in a stable state. However, although the method of encapsulating enzymes inside liposomes is already known, no studies have been done on Luc. In our study, we have encapsulated heat-stabilized recombinant Luc into liposomes and evaluated the amount and stability of the encapsulation. We have also constructed an immunoassay system for C-reactive protein using Luc-encapsulated liposomes as a label.

  • MALDI Matrix for Sensitive and High-Resolution Structural Analysis of Unmodified Sialylated Glycans and Glycoconjugates

    We have developed a matrix that can ionize sialylated glycans and glycoconjugates without modifying the carboxylic acid moiety of the sialic acids, and can analyze them with high sensitivity and resolution (reflector mode) without desorption of the sialic acid residue.

    Research

    Sialylation (addition of sialic acid) of glycans and glycoconjugates is an important biomarker involved in various biological phenomena such as development, differentiation, disease, infection, and immunity. MALDI (matrix-assisted laser desorption/ionization) is a simple and sensitive soft ionization method. However, the ionization efficiency of unmodified sialic acid-containing glycans is low, and there is a problem that the spectrum becomes complicated due to cleavage of sialic acids or other reasons. With this technique, we succeeded in measuring sialylated glycans and glycoconjugates with high sensitivity and high resolution without undergoing any modification process by improving the addition system to the conventional matrix while suppressing sialic acid desorption. With the change in the cleavage pattern and the increased sensitivity, TOF/TOF analysis and pseudo-MS3 analysis can now be performed using ultra-trace samples. This method does not require chemical modification and separation steps, and enables reaction tracking and rapid sample analysis.

  • Micro-/nano-patterns Created with Biomaterials

    Bio-based micro-/nano-patterns that mimic biological structures for application to cell culture tools and tissue regeneration

    Using biomaterials such as collagen and dental materials, we are producing micro-/nano-patterns that mimic biological structures. Depending on the shape of the pattern and the type of material, it can lead to the improvement of cell functions. While pursuing new possibilities, we aim to apply our technology to cell culture tools and periodontal tissue regeneration.

    Research

    In this study, we are using nanoimprinting to pattern typical biomaterials. We hope that the designed micro-/nano-scale shapes can be used to control cell functions and contribute to the development of novel cell culture tools and tissue regeneration.
    ● Comparison with conventional technology: It is characterized by unprecedented production of regular biomaterial patterns, and is expected to contribute to the discovery of new functions. (*Conventionally, irregular, flat or industrial plastics)
    ● Effectiveness: Patterning greatly improves the number of cells attached and the degree of elongation compared to flat surfaces. It also makes it easy to align cells in grooves. This can lead to the 3D construction of extracellular matrix (ECM).
    ● Future vision: We aim to regenerate tissues with a similar structure as that of living organisms by developing patterned materials not only in a flat plane but also in 2.5 and 3 dimensions through further layering.

  • Mitochondria-targeted Nanocapsules (MITO-Porter)

    Technology to introduce drugs, proteins and nucleic acids into mitochondria

    The mitochondrion is attracting attention as an organelle that contributes to the treatment of diseases, maintenance of beauty and health and the development of the life sciences. We have successfully developed a mitochondria-targeted nanocapsule (MITO-Porter) and are aiming to commercialize this nanocapsule.

    Research

    The mitochondria-targeted nanocapsules (MITO-Porter) in this study can pass through the cell and mitochondrial membranes to deliver target molecules inside the mitochondria. Conventional technologies using functional elements severely limit the size and type of molecules to be delivered, but the strategy using MITO-Porter, which encapsulates the target molecule, enables mitochondrial delivery independent of the molecular species.
    When we prepared MITO-Porter with GFP (green) encapsulated and observed intracellular fluorescence microscopy, we observed many yellow signals that overlap with mitochondria (red), confirming efficient molecular delivery inside the mitochondria. We have also succeeded in introducing genes and nucleic acids into mitochondria, which had been impossible with existing nucleic acid delivery agents (targeting the nucleus and cytoplasm). We are also developing nanocapsules that can be adapted to living organisms.

  • Multimedia Artificial Intelligence Technology Reaching Social Implementation

    Approaching the practical application of AI technology through industry-university collaborative research!

    With this research, we are developing artificial intelligence technology for multimedia data, mainly images, video, music, and audio. We are handling data related to medical images, social infrastructure data, materials science and other fields, mainly through industry-university collaborative research.

    Research

    We are not only conducting the world's most advanced artificial intelligence research, but also promoting research in interdisciplinary areas and taking on the challenge of solving real-world problems. Specifically, in medical imaging research, we have collaborated with many medical institutions in Japan to build AI technology that surpasses human diagnostic accuracy. In medical and civil engineering research, we have built Explainable AI (XAI), which not only enables learning of small amounts of data, a challenge in AI research, but also enables explanations of judgment results, making the technology usable in the real world. In recent years, we have also developed human-centric AI technology that can make decisions like humans by introducing information strongly related to human interests, such as human brain activity and eye gaze data, into the AI learning process.

  • Open Advanced Research Facilities Initiative (Project for Creation of Research Platforms and Sharing of Advanced Research Infrastructure)

    Microscopic imaging platform for atoms and molecules

    Promotion and expansion of the isotope microscope system installed at the Equipment Management Center for shared use by industry, academia and government.

    Research

    We invite, select and implement proposals for the effective use of stable isotope imaging technology, which is a special feature of the isotope microscope system, to expand it to industrial innovation.
    Upon hearing the word, “isotopes,” the concept of “age measurement” immediately comes to mind. Actually, until now, isotope microscopes have been used to analyze isotope ratios, primarily in minerals and other areas of space science. This is a result obtained by observing the as-is cross-section of the obtained sample. However, by changing the concept of the measurement method, we can expand the use of isotope microscopes to industrial application. In other words, by actively doping a target sample with an isotope element, rather than observing it “as such,” it becomes possible to measure the desired imaging we were unable to see before. The use of stable rather than radioactive isotopes also allows us to work safely.

  • Open Advanced Research Facilities Initiative NMR Shared Platform

    Program for promotion of shared use of advanced NMR facilities

    The Advanced NMR Facility is the largest NMR facility in Hokkaido, and is not only open to local industries, but also to industry, academia and research institutes nationwide.

    Research

    The Faculty of Advanced Life Science and the Faculty of Science of Hokkaido University play the central role in managing the Advanced NMR Facility. In cooperation with the Institute for the Promotion of Business-Regional Collaboration and the Global Facility Center of the Creative Research Institution, we aim to promote new applications, primarily in industry. For more information on the specifications of the 800 MHz solution NMR, 600 MHz solid-state NMR and other instruments, as well as application procedures for their use, please see our website. We hope that you will take advantage of the project to promote shared use of the Advanced NMR Facility at Hokkaido University.

  • Peptide and Glycopeptide Cyclization Technology

    Significant improvement of peptide cyclization efficiency by controlling hydrogen bonds

    By focusing on forming a hydrogen-bond network in the solvent, we have succeeded in both efficient peptide cyclization and improved solubility of poorly soluble peptides. This system can apply to drug discovery and molecular tool design.

    Research

    Cyclic peptides are an ideal molecular form for exploring biologically active compounds (drug discovery) and the design of molecular tools in life science. Cyclization of the peptide backbone can control their conformational stability, orientation, and symmetry. However, peptide cyclization requires specific dilution conditions and complex basic protection strategies. We found that combining a hydrogen-bond-controlled solvent system and a base-free condensation agent system enables the efficient cyclization of poorly soluble peptides under highly concentrated conditions. The simplicity of this technology gives a wide range of applications for drug discovery and life sciences by facilitating the free design and mass production of cyclic peptides.

  • Portable Liquid Chromatograph

    Battery-powered, ultra-light, ultra-compact chemical analyzer

    Using proprietary technology, we have miniaturized the pump, column and detector, all key components of liquid chromatography, realizing a compact, B5 size, lightweight and portable liquid chromatograph weighing 2 kg. This allows us to instantly obtain analysis results on the spot.

    Research

    The pump we have developed for liquid chromatography is based on electroosmotic phenomena and can operate for a long time on dry batteries. Since there is no mechanical drive, it is extremely compact and lightweight, and does not generate pulsating flow. Using microfabrication technology, the column and (electrochemical and UV) detectors are mounted on small amounts of substrate, the size of a business card. Conventional packing materials are used for the column, so the same analysis conditions as before can be applied directly without modification. The electrochemical detector uses a uniquely developed comb-shaped electrode. Although small in size, it has comparable sensitivity as conventional detectors. Liquid chromatographs currently used as the main instrument for chemical analysis are large and heavy, limiting their use to specific locations in the laboratory, but the instrument we have developed can easily be used anywhere. The amount of solvent used can also be reduced to 1/100 to 1/1000 of conventional detectors.

    Akihiko Ishida Assistant Professor
    Doctor of Engineering
  • Reduce Stress on the Liver to Prevent Liver Disease!

    To prevent lifestyle-related diseases of the liver (e.g., fatty liver, hepatitis, cirrhosis)

    We are analyzing the molecular mechanisms of organ stress, mainly in the liver, for the diagnosis, prevention, and treatment of lifestyle-related diseases. Using our unique optical imaging technology, we are conducting dynamic analysis to explore functional foods and develop new drugs from a new perspective.

    Research

    In recent years, the number of lifestyle-related diseases such as fatty liver and steatohepatitis has been steadily increasing. These conditions are generally unrecognized and difficult to prevent due to their slow progression and lack of subjective symptoms. However, since these diseases are known to progress to cirrhosis and hepatocellular carcinoma, prevention and suppression of progression are important.
    We are studying the molecular mechanisms of the progression of hepatic steatosis, injury, hepatitis, and liver fibrosis caused by various kinds of stress. At the same time, we are searching for functional foods and therapeutic agents to inhibit the progression of disease. Furthermore, we are attempting to conduct unique pathological analysis and construct an in vitro screening system for functional foods and drugs by applying optical imaging technology.

  • Reorganization of Public Facilities in an Era of a 30% Population Decline

    Grand design of “Machi no Seitai” and living areas

    In Hokkaido, it is expected that more than a hundred villages will disappear in the near future. “Machi no Seitai” is an attempt to optimize the size of local cities in a broad sense, in view of the era of a 30% population decline, while focusing on the reorganization of public buildings that remain unused or underutilized in local regions.

    Research

    The town of Kamishihoro in Kato-gun, Hokkaido, like other municipalities in Hokkaido, is facing a rapid population decline: from 10,309 in 1965 to about half that number in 2010. It is estimated that the population will decline to 3,222 by 2040. In 2012, taking this situation into consideration, the city established 10 themes for the creation of a city with a population of 5,000; and the first of these was to create a grand design for the layout of public facilities.
    The reorganization of public facilities in urban municipalities is generally implemented to ease financial pressures by controlling the number of facilities. However, Kamishihoro Town has different challenges and objectives. We are exploring the question of that kind of affluent lifestyle that can be achieved in a small town with a population below 10,000, and the role of public facilities to this end.

  • Simple Pathogen Measuring Devices

    Pathogens can be measured by simply adding samples to the kit.

    We have developed technology that allows measurement of the concentration of E. coli, coliforms, and enterococci within as early as 1 hour and as late as 12 hours after simply adding 0.1 mL of a sample (sewage, wastewater, food extract, drinking water) to the measurement kit and installing it in the device.

    Research

    Currently, the measurement of pathogenic bacteria requires a much time and labor, including the preparation of agar media, multiple dilutions of a large amount of sample, and 24-hour incubation. We have developed a kit that can measure pathogenic bacteria (fecal contamination indicator bacteria) such as E. coli, coliforms, and enterococci simply by injecting 0.1 mL of liquid sample or food extract. Compared to the current general bacteria measurement technology, this is an extremely simple technology that requires only mixing of the sample with the solution. The bacterial concentration is measured using a fluorescent dye. The fluorescent dye can be used even if the liquid is turbid, so the concentrations of various bacteria, even in turbid samples such as wastewater or food extracts, can be measured directly without any pretreatment.

  • Sonoporation: Development of a New Drug Delivery Method Using Ultrasound and Microbubbles

    Realization of tissue targeting capability at the cellular level

    We were the first in the world to show that, by irradiating cells with pulsed ultrasound while microbubbles of several microns in diameter are attached to the cells, we can temporarily increase the cell membrane permeability. We are now promoting research aimed at realizing drug and gene delivery to living organisms.

    Research

    ○ Acoustic perforation (sonoporation) using microbubbles and pulsed ultrasound: Pulsed ultrasound irradiation of microbubbles in contact with the cell membrane enables temporary perforation only at the attachment site (Fig. 1). We have realized a method to deliver drugs or genes into any desired position in the target cell by adding drugs or genes to the microbubbles and controlling the attachment site with optical tweezers.
    ○ Succeeding with therapeutic site identification and drug delivery by using microbubbles and an ultrasound system: A microbubble, which has the target function of adhering only to the cells to be treated, is injected into a vein. To identify the therapeutic site, the tissue where the bubbles have accumulated is detected using an ultrasound contrast method. Pulsed ultrasound waves are then generated to break the bubbles, allowing temporary perforation of the cell membrane and drug delivery (Fig. 2). By adding drugs or genes to the bubbles, highly efficient drug delivery only to the target cells can be realized.

  • Stabilization of Nanoparticles Using Cyclic Poly(ethylene Glycol)

    A novel stabilization method relying on the “topology” of polymers

    In this research, we developed a novel dispersion stabilization method for metal nanoparticles using cyclic poly(ethylene glycol). The research group has found that molecular aggregates consisting of cyclic polymers have excellent stability. By applying this phenomenon, the dispersion stability of nanoparticles can be enhanced.

    Research

    A large number of nanoparticle-based drugs are currently investigated, including drug delivery system (DDS) carriers, many of their surface is covered with biocompatible poly(ethylene glycol) (PEG). In this regard, we have found that gold nanoparticles (AuNPs) modified with cyclic PEG exhibit high dispersion stability at high salt concentrations. In other words, AuNPs treated with cyclic PEG with a molecular weight of 4000 retained their dispersion stability for one week or longer in a 180 mM NaCl solution, which is a higher concentration than physiological conditions, whereas AuNPs treated with linear PEG of the same molecular weight started aggregating and precipitating within 3 hours in a solution of only 45 mM NaCl. This novel method using cyclic PEG can be applied to a variety of nanoparticle-based drugs including contrast agents and magnetic nanoparticles.

  • Susceptibility Testing of Molecular-targeted Therapeutic Drugs

    Visualization technique of drug responsiveness in individual cells using fluorescence bioimaging

    Fluorescence bioimaging is a technique to visualize the cell behavior at the single cell level. Using this method, we have applied the imaging technology to visualize drug responsiveness and resistance, and to predict future drug responsiveness of patients.

    Research

    This diagnostic technique uses fluorescent proteins and a fluorescent biosensor based on the principle of F?rster resonance energy transfer (FRET).
    By visualizing the drug responsiveness at the single cell level with this biosensor, it has become possible to detect a very small number of drug-resistant cells. As a result, we have achieved a high concordance rate with the clinical course after administration and prediction of future drug responsiveness, both of which were not possible with conventional technology. This technology is not only the world’s first clinical application of fluorescent proteins, but also expected to help assure safety by selecting therapies with guaranteed efficacy. This will also bring economic benefits to medicine by reducing the financial burden on patients and the medical costs. We are now proceeding with this project for chronic myeloid leukemia, which is a blood cancer, as a model. In principle, this technology can be applied to various cancers.

  • Technology to Analyze Glycan Patterns Directly from Glycoproteins

    The world's first selective ionization technology for glycans that does not require pretreatment
    (This is a technology for which Hokkaido University is the sole applicant and sole inventor.)

    We have discovered the world's first mass spectrometry technique for selective ionization of glycans in complex macromolecules and mixtures such as glycoproteins and body fluids by the MALDI method. We have also demonstrated that this technique can be used for the direct analysis of glycans in complex mixtures such as egg white and body fluids.

    Research

    Glycan patterns on glycoproteins are important biomarkers because they are factors that determine the disposition of protein in the body. Until now, glycan pattern analysis has required complicated operations such as cutting, chemical modification, and purification of glycans. Mass spectrometry is an ultra-sensitive and high-resolution analytical technique that can directly ionize trace amounts of biomolecules. However, there has not been a method to selectively ionize glycoconjugates such as glycoproteins and glycans in complex macromolecules and mixtures such as body fluids, which requires the complicated pretreatment described above. We have achieved the world's first simultaneous selective cleavage and selective ionization of glycoconjugate glycans, and succeeded in the direct analysis of glycan patterns on glycoproteins. We have also demonstrated that this technique can be used to directly analyze glycan patterns in complex mixtures such as egg white.

  • Technology to Create Unique Glycan Derivative Libraries × Microarray Analysis System That Can Be Used Anywhere

    Original library using automated glycan synthesis technology × Microarray technology supporting on-site medical care and research

    Glycan-related interactions are important targets of infectious diseases and cancer diagnosis. We have developed a microarray system that can be used anywhere to utilize the libraries of glycans, glycoconjugates, glycan-related inhibitors, and their derivatives that have been constructed and accumulated in the process of developing automated glycan synthesis technology.

    Research

    Microarray technology is a technology that enables simultaneous comparative analysis of the interaction between a large number of compound libraries with well-defined structures and sequences and sample components. We also have the most advanced technology to design and produce our own carbohydrate compound libraries as molecules for microarray analysis based on our automated carbohydrate synthesis technology. The interaction information possessed by carbohydrates is widely used as biomarkers for in vitro diagnostics, such as blood types, serotypes such as O157, and cancer diagnostic markers (CAxx). In addition, we have succeeded in developing an independently powered mobile analyzer that can be used for online diagnosis, such as analysis of infection patterns associated with mutations in infectious diseases and detailed analysis of vaccine effects, by performing specimen collection and microarray analysis on the spot using a smartphone as a terminal.

  • Tumor Angiogenesis Inhibitor Screening System

    A cell-based screening assay system for the development of tumor angiogenesis inhibitors

    We aim to realize cell-based screening using tumor vascular endothelial cells, and contribute to the development of next-generation angiogenesis inhibitor therapies by overcoming problems of existing angiogenesis inhibitors (side effects, lack of companion diagnostics).

    Research

    Thanks to the development of molecular targeted therapies, antiangiogenic agents are now widely used. However, there are problems such as the lack of companion diagnostics to predict therapeutic effects and side effects due to injury to normal blood vessels.
    We have successfully isolated and cultured human tumor vascular endothelial cells and have identified specific markers that they express. Tumor vascular endothelial cells expressing these markers are valuable materials for cell-based screening of novel drugs and compounds, and help us identify new therapeutic targets and drugs that cannot be discovered by studies using conventional tumor cell lines or clinical tumor tissue fragments. Markers expressed by these tumor vascular endothelial cells can also be used as companion diagnostics. This will contribute to the realization of personalized treatment by selecting the target cases as well as the timing and duration of administration with angiogenesis inhibitors.

  • Understanding the Effects of Monoploidy on Animal Individual Development

    Toward the establishment of a single-fold system control technology for industrial use

    It is aimed to elucidate the mechanism by which the monoploid state, which has only one set of genomes, causes serious disorders in the development of individual animals, and to establish a technology for creating monoploid individuals that can be used for genetic engineering and strain improvement.

    Research

    The cells that make up the body of an animal cell are diploid, having two sets of genomes, one maternal and one paternal. In contrast, unfertilized eggs, which normally do not proliferate as such, become monoploid embryos with only the maternal genome, when they are activated to induce individual development (monogenesis). If monoploid individuals can be obtained from them, it will be very useful for genetic engineering and pure line creation. However, in vertebrates in general, monoploid embryos die due to the early developmental abnormality called “hemiparity syndrome,” so the use of monoploid embryo technology has not been realized yet. Using human cultured cells and early mouse embryos as models, we aim to clarify the effects of the monoploid state on developmental processes at the cellular level using molecular cell biology techniques. Based on these results, we aim to establish a cell manipulation method to eliminate the hemiploidy syndrome and to create viable monoploid individuals with stable traits.