A5021148242- Circadian rhythm and melatonin
- Genetics, Aging, and Longevity in Model Organisms
- Pluripotent Stem Cells Research
- Light effects on plants
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- Sleep and Wakefulness Research
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- Myasthenia Gravis and Thymoma
- Spaceflight effects on biology
- Gene Regulatory Network Analysis
- Photoreceptor and optogenetics research
- Single-cell and spatial transcriptomics
- Advanced biosensing and bioanalysis techniques
- Advanced Fluorescence Microscopy Techniques
- Microtubule and mitosis dynamics
- Lymphoma Diagnosis and Treatment
- DNA and Nucleic Acid Chemistry
- Cancer Treatment and Pharmacology
- Bacterial Genetics and Biotechnology
- Cell Image Analysis Techniques
- Dietary Effects on Health
- Viral Infectious Diseases and Gene Expression in Insects
- 3D Printing in Biomedical Research
The University of Tokyo
2018-2024
RIKEN Center for Biosystems Dynamics Research
2018-2024
Center for Systems Biology
2009-2010
RIKEN
2009
National Institutes for Quantum Science and Technology
2006
Japan Society for the Promotion of Science
2003
Genesis Research Institute
2000
National Institute of Genetics
1997-1998
A striking feature of the circadian clock is its flexible yet robust response to various environmental conditions. To analyze biochemical processes underlying this flexible-yet-robust characteristic, we examined effects 1,260 pharmacologically active compounds in mouse and human cell lines. Compounds that markedly (>10 s.d.) lengthened period both lines, also it central tissues peripheral cells. Most inhibited casein kinase Iε (CKIε) or CKIδ phosphorylation PER2 protein. Manipulation...
The identification of molecular networks at the system level in mammals is accelerated by next-generation mammalian genetics without crossing, which requires both efficient production whole-body biallelic knockout (KO) mice a single generation and high-performance phenotype analyses. Here, we show that triple targeting gene using CRISPR/Cas9 achieves almost perfect KO efficiency (96%-100%). In addition, developed respiration-based fully automated non-invasive sleep phenotyping system, Snappy...
Sleep regulation involves interdependent signaling among specialized neurons in distributed brain regions. Although acetylcholine promotes wakefulness and rapid eye movement (REM) sleep, it is unclear whether the cholinergic pathway essential (i.e., absolutely required) for REM sleep because of redundancy from neural circuits to molecules. First, we demonstrate that synaptic inhibition TrkA+ causes a severe short-sleep phenotype reduction mostly attributable shortened duration dark phase....
Hearing impairments are the most common symptom of congenital defects, and they generally remain intractable to treatment. Pendred syndrome, frequent syndromic form hereditary hearing loss, is associated with mutations in anion exchanger pendrin. Loss pendrin function as an thought be causative, but rodent models do not exhibit progressive deafness. Here, we report a degenerative phenotype exhibiting mutant aggregates increased susceptibility cellular stresses cochlear epithelial cells...
The reduced sleep duration previously observed in Camk2b knockout mice revealed a role for Ca 2+ /calmodulin-dependent protein kinase II (CaMKII)β as sleep-promoting kinase. However, the underlying mechanism by which CaMKIIβ supports regulation is largely unknown. Here, we demonstrate that activation or inhibition of can increase decrease almost 2-fold, supporting core regulator mammals. Importantly, show this depends on activity CaMKIIβ. A mutant mimicking constitutive-active...
Notch1 protein is a transmembrane receptor that directs various cell fate decisions. Active forms of consisting domain and an intracellular (Notch1TM) or only (Notch1IC) function as oncoproteins. To elucidate the effect abnormalities in radiation-induced lymphomagenesis, we determined structure gene examined frequency sites rearrangements mouse thymic lymphomas. The consists 37 exons, including three exons upstream previously reported exon 1. transcript starting from 1 was major whereas...
Background: The timing of the cell division in Escherichia coli is highly regulated, but its mechanism has not been identified. Previously we have found that cfcA1 mutation uncouples DNA replication and elevates frequency division. We further analysed structure role cfc genes cfcA11, a derivative cfcA1, another mutant, cfcB1. Results: mutants divided prior to ordinary stage produced many small cells with nucleoid. However, grew exponentially, length cycle initiation mass for chromosome were...
Abstract Deregulated V(D)J recombination-mediated chromosomal rearrangements are implicated in the etiology of B- and T-cell lymphomagenesis. We describe three pathways for formation 5′-deletions Notch1 gene thymic lymphomas wild-type or recombination-defective severe combined immune deficiency (scid) mice. A pair recombination signal sequence-like sequences composed heptamer- nonamer-like motifs separated by 12- 23-bp spacers (12- 23-recombination sequence) were present vicinity deletion...
The murine nuclear protein Np95 has been shown to underlie resistance ionizing radiation and other DNA insults or replication arrests in embryonic stem (ES) cells. Using the databases for expressed sequenced tags a two-step PCR procedure, we isolated human NP95, full-length homologue of cDNA, which consists 4,327 bp with single open reading frame (ORF) encoding polypeptide 793 amino acids 73.3% homology Np95. ORF NP95 cDNA is identical UHRF1 (ubiquitin-like containing PHD RING domain 1)....
ABSTRACT The ftsE (Ts) mutation of Escherichia coli causes defects in cell division and growth. We expressed alkaline phosphatase (PhoA) fusion proteins KdpA, Kup, TrkH, all which proved functional vivo as K + ion pumps, the mutant cells. During growth at 41°C, these were progressively lost from membrane fraction. reduction abundance inversely correlated with growth, but preformed stable indicating that molecules synthesized permissive temperature diluted a growth-dependent manner high...
There is an increasing demand for genetically modified mice produced without crossing, rapid phenotypic screening studies at the organismal level. For this purpose, generation of completely embryonic-stem-cell (ESC)-derived chimeric crossing now possible using a microinjection or aggregation method with 3i culture medium. However, ESCs into blastocyst, morula, 8-cell-stage embryos requires highly skilled operator. The easier alternative, but conventional protocol still special skills. To...
Abstract Although many reports suggest that aberrant regulation of cytokine signaling pathways via the interleukin‐2 receptor (IL‐2R) induces tumorigenic transformation, constitutively active IL‐2R in tumors has not been reported. We searched for genomic alteration IL‐2/15R β‐subunit gene ( IL‐2 / 15Rβ ) cytokine‐independent cell lines established from radiation‐induced mouse thymic lymphomas. In TL34 line and its primary tumor, one alleles was rearranged by insertion an intracisternal A...
Leucine-rich repeat kinase 2 (LRRK2) is the causal gene of autosomal dominant hereditary form Parkinson's disease (PD), PARK8. We have previously reported that induced pluripotent stem cells (iPSCs) from a PARK8 patient with I2020T LRRK2 mutation replicated to some extent pathologic phenotype evident in brain PD patients. In present study, we generated gene-corrected iPSCs line, KEIUi001-A, using TALEN-mediated genome editing. KEIUi001-A retained normal karyotype and pluripotency, i.e....
SUMMARY Both adult neural stem (type B) cells and ependymal E) in the mouse ventricular-subventricular zone (V-SVZ) are derived from slowly dividing (or quiescent) embryonic stem-progenitor (NPCs) that set aside during development. However, it has remained unclear whether fate diversification between type B E actually occurs embryogenesis. Here we performed single-cell transcriptomic analysis of NPCs identified cell subpopulations transcriptionally similar to or cells. The B- like appeared...