Laboratory of Genetic Engineering and Molecular Biology
On going research projects in our laboratory are (1) Establishment of transgenic chicken for the production of biopharmaceuticals (2)Mechanisms of anti-inflammatory effects of sialic acid binding lectin Siglec, and its relation to macrophage subclass differentiation.
Laboratory of Bioprocess Engineering
The cell is the basic structural and functional unit of all known living organisms. In human body, almost all diseases are caused by defective or insufficient cellular function. Invasion and metastasis are the halmarks of malignant tumors. Research of single cell function is strongly linking with diagnosis of disease.
Peptides are short chains of amino acid monomers linked by peptide bonds. Peptide is a part of protein, which takes an important role in cellular function, and it can bind to another protein or other macromolecule. Exploration of peptide with novel function is attractive in biological field.
Laboratory of Environmental Engineering
Environmental biotechnology utilizes functions of microorganisms for conserving the environment and would be an important key technology for sustainable development. Biodegradation of toxic chemicals, wastewater treatment, and bioremediation are important technologies using metabolisms of microorganisms. Biofuels, such as bioethanol, methane, and hydrogen, produced by microorganisms including yeasts, bacteria, and algae are expected as alternative energy that can be produced from organic wastes. Energy production is being integrated with cleaning technology using microorganisms.
Biocatalysts, such as microbial cells and enzymes synthesized by them, are applicable to chemical reactions under energy conserving natural conditions. Biocatalysts show high specificity in substrate recognition and reactions, thereby resulting in less production of byproducts that become wastes and decrease in reaction steps for obtaining final products. Drawbacks of biocatalysts, such as instability, fragility, complicated handling, and high production costs, are being solved by protein and metabolic engineering, immobilization technology, and synthetic biology.
Laboratory of Catalysis in Organic Synthesis
In the laboratory of Chemistry of Biologically Active Materials, the following researches are on going, (1) Design of artificial enzymes, called “Chemzymes”, based on acid–base combination chemistry and supramoleular chemistry in order to control enantioselectivity, stereoselectivity, regioselectivity, chemoselectivity, and substrate selectivity, (2) Modeling on the biochemical reaction systems or enzymatic reaction systems based on biomimetic chemistry, and (3) Optimization of the synthetic route for efficient synthesis of bioactive substances based on process chemistry and green & sustainable chemistry. Keywords: catalysis, biomimetic, bioactive, supramolecule, organocatalysts, organic synthesis, green chemistry
Laboratory of Biopolymer Chemistry
Various biomolecules created by life activity show their superior potentiality to us. In this laboratory, we design and create new supramolecules that further exceed natural materials by learning how natural molecules function in life. We are now developing new tools for future biotechnology and high-performance nano-materials by making full use of nucleic acid (DNA, RNA) and peptide.
- Development of photo-responsive oligonucleotides for the photo-regulation of biofunctions.
- Design and preparation of nano-assembly of functional molecules by use of DNA as a template.
- Development of highly sensitive fluorescent probes that can recognize the sequence of DNA and RNA.
- Insulator nucleotides for light-up of DNA
- Re-installed siRNA and XNA for new nucleic acid drugs
- Re-install of duplex towards the totally artificial duplex
- Experimental verification of theory with DNA
Laboratory of Structural biotechnology ( Synchrotron Radiation Research Center )
1. Delving into the molecular mechanism behind deep-sea bacteria’s pressure tolerance and its application
Many organisms live in the high-pressure environment, even at the bottom of the Mariana Trench, deepest location on the earth's surface. Those species has pressure tolerance of more than 1000 atm (1000 kg/cm2, 100 MPa). In general, hydrostatic pressure induces structural changes in proteins including denaturation, for which the mechanism has been attributed to water penetration into the protein interior. However, the molecular mechanisms of the pressure resistance are not well understood. We have been performing a high-pressure protein crystallography using the diamond-anvil cell (DAC) and synchrotron radiation. We intend to make high-pressure studies of several proteins, and reveal the principle of pressure resistance mechanism of the piezophilic organisms. In the future, it might be possible to create an original pressure resistant proteins based on accumulated knowledge.
2. Structural study of HIV/AIDS related proteins and its applications
In Japan, unfortunately, the incidence of new HIV infection is still increasing year by year. The chemotherapies should be continued for life-long period, and we must consider the appearance of resistance in the virus. To avoid such problem, it is quite requisite to understand how the virus develops resistance to drugs. And for the development of new anti-HIV therapies, analysis of the molecular mechanism on anti-HIV factors derived from the human host, such as APOBEC3s, are also performed using the X-ray protein crystallography.
Laboratory of Cell and Molecular Bioengineering (Graduate School of Pharmaceutical Sciences)
Regenerative medicine is the most recent medical therapeutic technology which enhances “regeneration” of patients’ damages and defects by transplanting in vitro cultured cells or by implanting regenerative factors. The recent stem cell technologies, such as embyonic stem cells (ES cells), induced pluripotent stem cells (iPS cells), and mesenchymal stem cells (MSCs), are the most expected cell sources for previously incurable symptoms. Also, tissue engineering technology, which combines cell culture engineering, bio-polymer designs, and cell biology, is another research field that expands the regeneration of complex tissues and organs. More and more new technologies based on engineering approaches are required to advance this field.
Pharmaceutical Drug Screening:
Basic research and developments are the basal potential to explore new molecules and target mechanisms of diseases. The biological approaches in such medicinal researches are commonly focused on two fields of professions. One is the molecular understanding of target molecules that relates to the diseases. Comprehensive understanding of gene profiles and protein profiles combined with structural information from the molecular assays provides deep understanding of the mechanism and leads to the design of molecular targeting drugs. These days, molecular researches combined with bioinformatics utilizing the high-dimensional information is greatly contributing for advances. The other is the high throughput assay technology, combining the biology together with automated technological system, for exploring new molecular effects. Such assay, regarded as high throughput screening (HTS), is a cross-over development of engineering-based technologies.