Naoya Ieda

Development of molecular technology to photomanipulate blood flow from outside the body

Researcher

Naoya Ieda

Outline

The cardiovascular system is an important organ for maintaining homeostasis of the living body. My research aims to develop compounds that can control the release of nitric oxide, a signaling molecule that triggers vasorelaxation, by light, and to establish technologies to control nitric oxide dynamics at the cellular level and to manipulate blood flow at the animal level. This technology is expected to become a new treatment paradigm for cardiovascular diseases that can be improved by blood flow.

Hiroshi Inaba

Cell manipulation by photocontrol of microtubules based on protein encapsulation

Researcher

Hiroshi Inaba

Outline

Microtubules are one of the cytoskeletons and play important roles in life such as cell shape, strength, motility, and division. We have previously developed peptides that bind to the inner surface of microtubules and have used them to introduce various molecules inside microtubules. Through these studies, we have realized that the structures and properties of microtubules could be modulated by the introduced molecules. In this research, vaious proteins will be introduced inside microtubules in living cells by using the peptide and the binding property of the proteins will be modulated by light. The light-induced changes of microtubules will be used to manipulate cell structures and functions.

Richiro Ushimaru

Biosynthetic studies on the antibiotic production in a biocontrol agent

Researcher

Richiro Ushimaru

Outline

Biocontrol Agrobacterium produces nucleoside natural products that inhibit the growth of plant pathogens. However, little is known about how the antibiotics are generated. In this study, I will establish the biosynthetic pathway of the antibiotics produced by Agrobacterium and determine the catalytic mechanisms of the enzymatic transformations. Furthermore, I aim to develop a method for creating unnatural nucleosides by exploiting the natural biosynthetic system.

Tomoko G. Oyama

Development of Artificial ECM by Novel Crosslinking Technique for Regulating Cellular Functions

Researcher

Tomoko G. Oyama

Outline

Various cues from the extracellular matrix (ECM), a hydrogel of proteins and polysaccharides, can regulate cellular functions in vivo. The purpose of this study is developing artificial ECM which can mimic and control the key features of native ECM. I will develop a novel crosslinking technique to form hydrogels of ECM-derived macromolecules. The artificial ECM will be useful for strategically inducing and controlling cellular functions in vitro.

Shunta Kimura

Identification the compounds which regulate cell differentiation of multicellular cyanobacteria

Researcher

Shunta Kimura

Outline

Cyanobacteria are considered the ancestors of chloroplasts. Several filamentous strains of cyanobacteria can differentiate into vegetative cells with photosynthetic abilities, heterocysts with nitrogen fixation abilities, motile hormogonia, and dormant akinetes. They can be considered as multicellular organisms. The triggers that regulate cell differentiation have not been elucidated. This project isolates and identificate the compounds which regulate cell differentiation of filamentous cyanobacteria. Regulatory substances should be exchanged across the cell-cell junctions in the filaments of the trichomes. The similarity and difference between the mechanisms of cell-cell communication of cyanobacteria and plants can be discussed.

Daiki Takahashi

Autophagy research with a new direction for drug discovery

Researcher

Daiki Takahashi

Outline

I have developed a method for clearance of intracellular molecules via selective autophagy, called AUTAC. In this study, I will focus on the involvement of intracellular phase separation in selective autophagy. In the future, I would like to challenge the control of phase separation using small molecules.

Noriko Saito-Tarashima

Development of antibody-oligonucleotide conjugates that induce immunogenic cell death

Researcher

Noriko Saito-Tarashima

Outline

Immunogenic cell death (ICD) is a type of cell death that induces immune responses, and is expected to be applied to cancer immunotherapy and infectious disease treatment. In this study, I will develop a method for inducing ICD specifically in targeted cells using antibody-oligonucleotide conjugates.

Shusuke Tomoshige

Expansion of Chemical Protein Degradation Toolbox

Researcher

Shusuke Tomoshige

Outline

Chemical protein degradation is the technology to lower the levels of protein of interest using compounds hijacking a protein degradation machinery. Because of its selective, rapid, reversible activity, the technology is expected to be applied in the research area of life sciences and medicinal chemistry; however it lacks generality at this point. To confer generality to the protein degradation technology, expanding toolbox is required. In this project, I develop novel protein degradation technologies utilizing various degradation machineries which are not utilized ever.

Kengo Nomura

Orchestration of multicellular information mediating attractive salty taste

Researcher

Kengo Nomura

Outline

We are tended to ingest excessive amount of salt (NaCl), because of it’s highly palatable taste. However, cellular and molecular mechanisms mediating attractive salty taste in tongue are longstanding puzzles. I try to identify chloride ion-sensor cells and elucidate the cellular mechanisms controlling attractive salty taste, by establishing technological strategies to manipulate targeted cells with specific function. The ultimate goal of this project is to obtain the target chemicals that control attractive salty taste, and to realize a healthy society with co-exisitence of happy to eat and reduced dietary salt.

Shoko Hashimoto

Elucidation of the function of rod-shaped microglia in the process of neurodegeneration

Researcher

Shoko Hashimoto

Outline

Microglia cells play important roles in the process of neurodegeneration by changing their cell morphology. “Rod-shaped microglia”, which has an elongated cell body, appears at an early stage of neurodegeneration in a mouse model that displays brain shrinkage. However, the function of rod-shaped microglia in neurodegeneration is not well understood. In this study, I will characterize gene expression profiles of rod-shaped microglia by next generation sequencing, and investigate its functions in neurodegeneration using a mouse model.

Tetsuya Hirata

Mechanisms for controlling glycan structures of GPI glycolipid

Researcher

Tetsuya Hirata

Outline

Glycosylation, a major posttranslational modifications of proteins, regulates protein functions and localizations. It is well known that abnormal glycosylation patterns are deeply related to disease developments and aggravations. Therefore, controlling the glycan structures will be potential therapeutic ways for various diseases. While biosynthetic pathways for various types of glycosylation have been established, it is largely unknown and the most challenging themes in the glycobiology field how diversity of glycan structures are generated. In this project, I am going to elucidate the mechanisms how variety of glycan structures of GPI, a posttranslational modification of proteins by a glycolipid, are generated from the novel aspect of the intracellular protein transport system.

Yosuke Fukutani

Novel activation mechanism of mammalian olfactory receptors induced by covalent modification

Researcher

Yosuke Fukutani

Outline

The olfaction of animals occurs when the chemical bonds form between odor molecules and olfactory receptors (ORs) expressed in olfactory sensory neuron cells. Since there are innumerable odor molecules in the environment and also hundreds of ORs of mammal, it is expected that various intermolecular bonds can cause activation of ORs. In this project, I focus on the novel activation mechanism of ORs with the covalent modification that occurs between the ORs and odor molecules. I attempt to elucidate the molecular recognition mechanism of the ORs that respond to highly active odor molecules.

Mizuki Honda

Unraveling the regulatory mechanism of spatial gene expression using chemically based method

Researcher

Mizuki Honda

Outline

During brain formation, gene expression is under strict spatial-temporal regulation. Therefore, in order to unravel how this regulation of works, a profiling technology is necessary with enable us to relate spatial information with gene expression. With this background, the goal of this study is to develop a chemically based method to clarify how spatial-temporal regulation of gene expression works.

Shiho Makino

Selective mRNA degradation by autophagy in yeast

Researcher

Shiho Makino

Outline

Synthesis and degradation of cellular constituents must be balanced to maintain cellular homeostasis, especially during adaptation to nutrient starvation. The role of autophagy in the degradation of proteins and organelles is well-characterized. However, autophagy-mediated RNA degradation in response to starvation and the preference of such RNA degradation have not been examined. I will investigate preference of mRNA degradation by autophagy and their physiological role in various starvation conditions in yeast. Additionally, I will evaluate localization and dynamics of autophagy-targeted mRNA using live imaging. I seek to uncover a novel functions of autophagy in RNA metabolism.

Kenichi Matsuda

Enzymatic synthesis of small cyclic peptide

Researcher

Kenichi Matsuda

Outline

Small cyclic peptides exhibit high metabolic stability and absorption. However, chemical cyclization of short peptide is challenging due to its linear conformation. PBP-type TE is a newly identified peptide cyclase that is specialized for short peptide. The aim of this study is to elucidate catalytic mechanism of PBP-type TE family and rationally manipulate their substrate scope to develop an improved biocatalyst with broad substrate tolerance. I will further utilize the cyclase gene to construct an artificial biosynthetic route for small cyclic peptides in microbial cell. These studies should facilitate highly accurate, easily scalable, environmentally friendly approach for production of small cyclic peptide.

Natsuko Miura

Elucidation of the metabolic control mechanism by the intracellular assembly of enzymes

Researcher

Natsuko Miura

Outline

Various metabolic enzymes, including the glycolytic enzyme enolase, form reversible aggregates in eukaryotic cells. These aggregates are formed in response to environmental changes, such as hypoxia, and regulates cell metabolism. We previously reported that the specific amino acid sequence of an enzyme is important for the formation of some aggregates. In this study, I develop molecular tools that can freely control the assembly and dispersal of enzyme aggregates. Through the development of tools, this study aims to elucidate the molecular mechanism of aggregate formation that enables the metabolic control in cells.

Kumi Morikawa

Development of optogenetics systems enable single cell lineage tracing and genome editing during mammalian embryogenesis

Researcher

Kumi Morikawa

Outline

Mammalian embryogenesis is a dynamic process taking place in three-dimensions, and progresses along a certain timeframe. Therefore, analysis methods such as live cell imaging or genome editing are required for higher spatiotemporal resolution for precise analysis. In this project, I propose new optogenetic approaches, which trace cell lineage, edit the genome and change particular gene expression patterns in single cells by using photoactivatable Cre recombinase (PA-Cre) in mouse embryo and human organoid derived from induced pluripotent stem cells. This proposed research will provide new insights into early embryogenesis and demonstrate novel optogenetic techniques for single cell analysis including cell lineage tracing and genome editing.

Momo Morikawa

Elucidation of cell-cell transmission mechanism of oxidative stress in intractable neurological diseases

Researcher

Momo Morikawa

Outline

Multicellular transmission of cell death signals is expected to be involved in the etiology of neurodegenerative diseases in which many neurons die almost at the same time. Since a point mutation of the intracellular molecular motor was identified in the family of Charcot-Marie-Tooth disease, which is one of such neurodegenerative diseases, I will focus on elucidating the extracellular release mechanism of oxidative stress-increased mitochondria fragment as mitochondrial derived vesicles (MDVs) by the mutant molecular motor. I will aim to figure out a new relationship between intracellular transport by the molecular motor and extracellular vesicle release, which is deeply involved in the progression of neurodegenerative diseases.

Hiroshi Yamagishi

Biocompatible laser oscilators for long term cell tracking

Researcher

Hiroshi Yamagishi

Outline

Spherical or disk lasor oscilators implanted inside biological cells work as a optical barcode that identifies individual cells and enables spaciotemporal tracking of the cells. The lasor oscilators utilized so far are, however, mostly composed of bio-imcompatible materials such as inorganic alloys or polystyrene becuase biocompatible materials are typically inferior in terms of the optical and morphological properties. We have been focusing on the self assembly of a series of organic polymers and revealed their excellent laser oscilting capabilities. In this research, I am planning to apply our method to biopolymers and bio-compatible polymers with the aim of supressing the cell toxitiy and enabling long term cell tracking.