Sefan Asamitsu

Development of genome-wide mapping methods of higher-order structures of DNA in mouse brain

Grant No.：JPMJAX2111

Researcher

Sefan Asamitsu

Outline

The guanine quadruplex (G4), one of the higher-order structures on genomic DNA, has been implicated in biological events such as transcription and replication, but its precise role has not yet been elucidated due to a lack of well-established analytical methods. In this study, we will develop a method that can define the formation behavior of G4DNA structures in mouse brain by combining our original technology with single-cell analysis technology, opening up a new field of G4 biology.

Kenji Iemura

Elucidation of the mechanism of cell-to-cell transmission of chromosomal instability

Grant No.：JPMJAX2112

Researcher

Kenji Iemura

Outline

The discrepancy between the accumulation of aneuploid cells in tumors and the survival of aneuploid cells in the experimental conditions is called the aneuploidy paradox. Chromosomal instability (CIN), in which the number and structure of chromosomes change with cell division, is the leading cause of aneuploidy. In this study, I will identify extracellular liquid factors that induce the reduction of kinetochore phosphorylation, which is the fundamental phenotype of CIN. Furthermore, the induction mechanism of CIN by this factor will be investigated to clarify the process of CIN-mediated genetic heterogeneity in tumors.

Tatsuya Ikenoue

Constraction of target-specific degradation organella using LLPS inducer peptide

Grant No.：JPMJAX2113

Researcher

Tatsuya Ikenoue

Outline

Liquid-liquid phase separation (LLPS) of proteins is known as an important phenomenon that forms membraneless organelle in cells and is involved in a wide variety of cellular functions and regulations. This project aims to create artificial clearance organelles, which condense and degrade target proteins, by applying novel peptides which induce LLPS of target protein. By means of the RaPID system, one of the most powerful peptide screening technologies, I will develop bifunctional peptides to achieve degradation of target protein with high specificity and efficiency through LLPS.

Mizuki Endo

Thermogentic control of intracellular signaling by ultrasound

Grant No.：JPMJAX2114

Researcher

Mizuki Endo

Outline

Spatiotemporal regulation of dynamic intercellular signaling is fundamental to homeostasis in our body. The present research aims to develop a novel analytical method to control intercellular signaling in deep tissue using local heat generation by focused ultrasound. It includes the generation of thermogenetic module that controls protein-protein interaction by heat, and the development of thermogenetic system that modulates intercellular signaling.

Jing Wu

Elucidation of hormones in higher fungi

Grant No.：JPMJAX2115

Researcher

Jing Wu

Outline

The aim of this project is to discover “mushroom hormones (molecules that are commonly endogenous to mushrooms and control their life cycle through a common mechanism)”, especially “fruiting-body inducing hormones” by the following three aproaches. Aproach 1: Search for fruiting body-inducing compound(s) in fruiting liquid (FL) Aproach 2: Verification of “fairy chemicals” as hormones in mushrooms Aproach 3: Verification of the “one of mushroom hormones is a steroid” hypothesis

Takeshi Sawada

Development of a new chemical manipulation technique for investigating synaptic function

Grant No.：JPMJAX2116

Researcher

Takeshi Sawada

Outline

In many psychiatric disorders, abnormalities in synapse-related genes and morphology of spines, the structural basis of synapses, have been reported. However, the specific effects of synaptic alterations on the mental activity of individuals are still unknown. In this study, I propose a new spine and synapse manipulation technique using chemical methods to causally examine the effects of synaptic changes. Furthermore, through its application, I aim to elucidate the responsible synaptic basis for depressive symptoms.

Kouhei Shimizu

Investigation and application of linear ubiquitin code-regulated host defense system

Grant No.：JPMJAX2117

Researcher

Kouhei Shimizu

Outline

The spatiotemporal specific protein ubiquitination regulates multiple cellular functions by generating various ubiquitin linkages, called ubiquitin code. LUBAC is an only ubiquitin ligase, which specifically generates the N terminal Met1 linked linear ubiquitin chain. Moreover, LUBAC plays a crucial role on the regulation of host defense system, and that is referred as linear ubiquitin code. In this study, I will elucidate the host defense system controlled by LUBAC and its various regulators from a molecular pathophysiological basis. Furthermore, I will aim to study on the application of innovative chemical technology targeting linear ubiquitin code and identify novel chemical seeds to treatment diseases.

Kosuke Shiraishi

Unraveling the regulatory mechanism of mRNA dynamics in the methylotrophic yeasts towards enhanced production of heterologous proteins

Grant No.：JPMJAX2118

Researcher

Kosuke Shiraishi

Outline

Objectives of the research is to understand the roles and molecular components of cytosolic foci like RNA granules in the methylotrophic yeast and to disclose the impact of such foci on the methanol-inducible gene expression through analyses of intracellular dynamics, molecular interaction and transcript-level expression. Based on the results obtained, I will verify the possibility of modulating the gene expression level of interest through regulating the mRNA dynamics in the cytosol.

Chie Suzuki

In vivo imaging for complement activation

Grant No.：JPMJAX2119

Researcher

Chie Suzuki

Outline

The main purpose of this project is to develop a positron emission tomography probe for complement activation, which cause neuron phagocytosis by microglia in the brain. In vivo imaging for complement activation would enable specific evalution of microglial phagocytosis in distinction from the other microglial actions, and would be useful for understanding the pathophysiology of neuronal deseases and development of novel diagnostic and therapeutic methods for neuronal diseases.

Ryo Tanifuji

Chemo-enzymatic hybrid synthesis of mid-sized molecules regulating transcriptions.

Grant No.：JPMJAX211A

Researcher

Ryo Tanifuji

Outline

To regulate transcriptions selectively and rationally, mid-sized molecules bearing various macrocycles were designed based on natural products’ structure. Chemoーenzymatic hybrid process allows for the rapid and flexible synthesis of designed molecules that covalently bind to DNA. Further modifications of macrocycles through [4+2] cycloaddition, N-alkylation and Huisgen cycloaddition will result in transcription controls by attaching extra units to interact with nuclear proteins.

Taka-aki Tsunoyama

Development of quantitative super resolution microscopy: superPAINT and elucidation of signal integration platform on the plasma membrane

Grant No.：JPMJAX211B

Researcher

Taka-aki Tsunoyama

Outline

I recently found a candidate of signaling platform on the plasma membrane, which integrates multi-signaling pathways. The first aim of this project is unveiling the mechanisms of formation and function of this newly found platform. For visualization and quantitative analysis of this platform, new quantitative microscopy to count the single molecules in the cluster structure is required. The second aim is to develop this new method which I termed superPAINT.

Yoshihide Tokunou

Investigation and control of cell-death-triggered electrical conduction in biofilm

Grant No.：JPMJAX211C

Researcher

Yoshihide Tokunou

Outline

Controlling the metabolism of bacteria has implications with various biological scientific fields; e.g. suppression of infectious diseases and improvement of the efficiency of biofuel production. However, it is difficult to control the metabolism once bacteria develop biofilm, which is the form in the environment and human body. In this research, based on our finding that small portion of bacteria actively proceed cell death activating the metabolism of the entire biofilm, we will create a technology for controlling biofilm metabolic activity.

Yosuke Niko

Development of Ultra-bright Fluorescent Probes for Visualizing Intravital Lysosome Dynamics

Grant No.：JPMJAX211D

Researcher

Yosuke Niko

Outline

Exosomes are extracellular vesicles and have attracted attention for their potential application to the diagnosis and treatment of various diseases. However, the observation of their intravital dynamics has been difficult so far. In this project, I will develop ultra-bright fluorescent probes which efficiently emit fluorescence under tissue-penetrative long-wavelength laser excitation by utilizing pyrene as a π-electron conjugated system. The combination of such fluorescent probes and a two-photon excitation fluorescence microscope is expected to enable the tracking of intravital exosomes.

Ayaka Harada

Cellular energy utilization and molecular evolution toward multicellularity

Grant No.：JPMJAX211E

Researcher

Ayaka Harada

Outline

Multicellularization occurred during an early stage in animal evolution, and is the most important evolutionary factor in producing diverse phyla. By focusing also on diversity among cellular energy utilization mechanisms, we will explore the actual state of biological systems, and the origin of multicellular organisms, an early step in the evolution of humans.

Manabu Bessho-Uehara

Discovering the second example of kleptoprotein

Grant No.：JPMJAX211F

Researcher

Manabu Bessho-Uehara

Outline

Kleptoprotein is a phenomenon that an organism uptake and utilize a functional protein from its prey item. This phenomenon was firstly discovered in a luminous fish, Parapriacanthus ransonneti. Kleptoprotein might be occur in other organisms, providing a convergent evolution of biological function although no instance has been found so far. In this project, I seek a new animal that possesses kleptoprotein.

Yuuki Horii

Development of application method of hibernation-like alternative splicing mechanisms

Grant No.：JPMJAX211G

Researcher

Yuuki Horii

Outline

Although body temperature of hibernator drops to less than 10 degrees, normal sinus rhythm is maintained during hibernation. Moreover, hibernators avoid various damage including the ischemia injury. I focus on Cold- shock protein. This protein participates in posttranscription regulation of various protein and can be important for the property of damage-tolerance in hibernators. I have found an interesting alternative splicing in one of the cold shock proteins during hibernation. My study aims to confer damage-tolerant property on non-hibernators by the mechanisms of hibernation-like alternative splicing of Cold shock protein.

Takahiro Masuya

Creation of “light-driven” mitochondrial respiratory complex I by chemical modifications

Grant No.：JPMJAX211H

Researcher

Takahiro Masuya

Outline

Mitochondrial respiratory complex I is a proton pump that is driven by oxidoreduction of respiratory substrates. This enzyme plays a critical role in ATP biosynthesis (energy production) in mitochondria. In this study, to aim at regulating ATP biosynthesis in mitochondria by light in the future, I will try to change complex I from a “redox-driven” to “light-driven” proton pump using site specific chemical modification techniques.

Ryota Yamagami

Development of a novel nucleic acid enzyme that efficiently functions inside cells

Grant No.：JPMJAX211I

Researcher

Ryota Yamagami

Outline

RNA plays a critical role in gene expression, and thereby RNA dysfunction often causes human diseases. For example, the deletion of N7-methylguanosine in RNA causes Down syndrome and microcephaly primordial dwarfism. In this project, I will develop a new system wherein nucleic acid enzymes can work efficiently in cells. I will also develop innovative tools which regulate cellular methylome by creating new nucleic acid enzymes that control and alter the function of RNA. These tools will be applied to RNA therapeutics.

Moe Yokoshi

Elucidating the dynamics of transcriptional regulation and genome organization by insulators

Grant No.：JPMJAX211J

Researcher

Moe Yokoshi

Outline

In order to address the functional importance of genome structure in gene expression, I will develop quantitative live imaging analysis to visualize impacts of chromosome topology on transcriptional regulation in living Drosophila embryo. In addition, this study focuses on the insulators and their binding proteins that are thought to be required for 3D genome organization. I aim for establishment of fundamental basis on the relationship between transcriptional dynamics and the physical properties of the insulator proteins such as liquid-liquid phase separation.

Tatsushi Yokoyama

Analysis of orphan GPCRs using a newly developed sensor.

Grant No.：JPMJAX211K

Researcher

Tatsushi Yokoyama

Outline

Orphan G protein-coupled receptors (oGPCRs) in the brain are considered as promising therapeutic targets for neuropsychiatric diseases. However, little is known about the roles of the oGPCRs in momentarily changing information processing. Here, we combine development of a genetically encoded sensor with advanced imaging techniques to reveal the dynamic aspects of oGPCRs.