Updated on 2026/03/11

写真a

 
AIZAWA YASUNORI
 
Organization
School of Life Science and Technology Associate Professor
Title
Associate Professor
External link

News & Topics

Degree

  • Doctor of Pharmaceutical Science ( Kyoto University )

Research Interests

  • Genome minimization

  • Genome design

  • large-scale genome engineering

Research Areas

  • Life Science / Cell biology

  • Life Science / Molecular biology

  • Life Science / Genome biology

Research History

  • Tokyo Institute of Technology   School of Life Science and Technology   Associate Professor   Ph.D.

    2017.10

      More details

  • Tokyo Institute of Technology   Center for Biological Resources and Informatics   Associate Professor (Lecturer)

    2005 - 2017.9

      More details

  • National Institute of Advanced Industrial Science and Technology   Visiting Scientist

    2005 - 2010

      More details

  • Johns Hopkins University   JHMI Department of Molecular Biology and Genetics   Postdoctral Fellow

    2002 - 2005

      More details

  • Howard Hughes Medical Institute / Columbia University   Department of Biochemistry and Molecular Biophysics   Research Associate

    2000 - 2002

      More details

  • Columbia University   Department of Biochemistry and Molecular Biophysics   Postdoctoral Scientist

    1999

      More details

▼display all

Professional Memberships

Papers

  • Biallelic genome engineering to create isogenic induced pluripotent stem cells modeling Huntington's disease.

    Hikaru Kurasawa, Yuta Matsuura, Riho Yamane, Tomoyuki Ohno, Yasunori Aizawa

    Genes & genetic systems   100   2025.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    We developed Huntington's disease (HD)-modeling induced pluripotent stem cells (iPSCs) by genome engineering of iPSCs from healthy donors. For this, we established a homologous-recombination-based biallelic substitution technique called the allele-specific universal knock-in system (asUKiS). asUKiS allows for scarless and allele-by-allele substitution of the entire region encompassing not only the polyQ repeat but also the associated genetic modifiers surrounding the repeat region, allowing us to generate five iPSC lines with identical genetic modifiers on both alleles, differing only in polyQ repeat numbers. All cell lines were validated by allele-specific genotyping to confirm the precise engineering of both alleles. Even for modeling autosomal dominant diseases, our approach of employing biallelic modification offers the distinct advantage of enabling investigation of the effects of specific genomic mutations with minimal interference from genetic background noise.

    DOI: 10.1266/ggs.25-00016

    PubMed

    researchmap

  • Versatile Methodology for Efficient Large-sized DNA Delivery Between Microorganisms Without In vitro Purification. International journal

    Shinya Kaneko, Hiromi Fukushima, Misako Nakahama, Kenji Tsuge, Jun Ishii, Yasunori Aizawa, Mitsuhiro Itaya, Akihiko Kondo

    Journal of molecular biology   437 ( 17 )   169289 - 169289   2025.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Purified DNA plasmids traditionally used for microbial transformation have been supplanted by extracellular plasmids released via host bacterial lysis, offering an alternative approach for DNA-plasmid delivery. Specifically, shuttle vector plasmids liberated from host Bacillus subtilis were directly employed for the transformation of chemically competent cells Escherichia coli, eliminating the need for biochemical purification. This unconventional DNA delivery technique, referred to as 'Cell Lysis Technology to provide Transformable Extra-cellular DNA; CELyTED', has been successfully adapted for the transformation of microorganism Saccharomyces cerevisiae as well. The protocol includes optimized conditions for efficient cell lysis of the donor host cells. Notably, ' CELyTED ' enables the introduction of large-sized DNA plasmids exceeding 50 kb into target microorganisms mitigating the potential adverse effects of physical shearing during the purification process. This simplicity in the delivery protocol makes it versatile for both prokaryotic and eukaryotic microorganisms, establishing a fundamental platform in the synthetic genome field. Our study demonstrates the feasibility of introducing large DNA plasmids into cells E. coli and S. cerevisiae using the lysate of donor host cells, showcasing the potential of 'CELyTED ' as a streamlined approach in genetic transformation methodologies.

    DOI: 10.1016/j.jmb.2025.169289

    PubMed

    researchmap

  • Generation of Monosomy 21q Human iPS Cells by CRISPR/Cas9-Mediated Interstitial Megabase Deletion. International journal

    Masaya Egawa, Narumi Uno, Rina Komazaki, Yusuke Ohkame, Kyotaro Yamazaki, Chihiro Yoshimatsu, Yuki Ishizu, Yusaku Okano, Hitomaru Miyamoto, Mitsuhiko Osaki, Teruhiko Suzuki, Kazuyoshi Hosomichi, Yasunori Aizawa, Yasuhiro Kazuki, Kazuma Tomizuka

    Genes to cells : devoted to molecular & cellular mechanisms   30 ( 1 )   e13184   2025.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Missing an entire chromosome or chromosome arm in normal diploid cells has a deleterious impact on cell viability, which may contribute to the development of specific birth defects. Nevertheless, the effects of chromosome loss in human cells have remained unexplored due to the lack of suitable model systems. Here, we developed an efficient, selection-free approach to generate partial monosomy in human induced pluripotent stem cells (iPSCs). The introduction of Cas9 proteins and a pair of gRNAs induces over megabase-sized interstitial chromosomal deletions. Using human chromosome 21 (HSA21) as a model, partial monosomy 21q (PM21q) iPSC lines with deletions ranging from 4.5 to 27.9 Mb were isolated. A 33.6 Mb deletion, encompassing all protein-coding genes on 21q, was also achieved, establishing the first 21q monosomy human iPSC line. Transcriptome and proteome analyses revealed that the abundances of mRNA and protein encoded by the majority of genes in the monosomic regions are half of the diploid expression level, indicating an absence of dosage compensation. The ability to generate customized partial monosomy cell lines on an isogenic, karyotypically normal background should facilitate the gain of novel insights into the impact of chromosome loss on cellular fitness.

    DOI: 10.1111/gtc.13184

    PubMed

    researchmap

  • Manipulating the 3D organization of the largest synthetic yeast chromosome. International journal

    Weimin Zhang, Luciana Lazar-Stefanita, Hitoyoshi Yamashita, Michael J Shen, Leslie A Mitchell, Hikaru Kurasawa, Evgenii Lobzaev, Viola Fanfani, Max A B Haase, Xiaoji Sun, Qingwen Jiang, Gregory W Goldberg, David M Ichikawa, Stephanie L Lauer, Laura H McCulloch, Nicole Easo, S Jiaming Lin, Brendan R Camellato, Yinan Zhu, Jitong Cai, Zhuwei Xu, Yu Zhao, Maya Sacasa, Marcus B Noyes, Joel S Bader, Samuel Deutsch, Giovanni Stracquadanio, Yasunori Aizawa, Junbiao Dai, Jef D Boeke

    Molecular cell   83 ( 23 )   4424 - 4437   2023.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Whether synthetic genomes can power life has attracted broad interest in the synthetic biology field. Here, we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp yeast chromosome resulting from extensive genome streamlining and modification. We developed megachunk assembly combined with a hierarchical integration strategy, which significantly increased the accuracy and flexibility of synthetic chromosome construction. Besides the drastic sequence changes, we further manipulated the 3D structure of synIV to explore spatial gene regulation. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Lastly, we tethered synIV to the inner nuclear membrane via its hundreds of loxPsym sites and observed transcriptional repression of the entire chromosome, demonstrating chromosome-wide transcription manipulation without changing the DNA sequences. Our manipulation of the spatial structure of synIV sheds light on higher-order architectural design of the synthetic genomes.

    DOI: 10.1016/j.molcel.2023.10.015

    PubMed

    researchmap

  • Development of an isogenic human cell trio that models polyglutamine disease.

    Tomoyuki Ohno, Takeshi Nakane, Taichi Akase, Hikaru Kurasawa, Yasunori Aizawa

    Genes & genetic systems   98 ( 4 )   179 - 189   2023.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Polyglutamine (polyQ) diseases are rare autosomal-dominant neurodegenerative diseases associated with the expansion of glutamine-encoding triplet repeats in certain genes. To investigate the functional influence of repeat expansion on disease mechanisms, we applied a biallelic genome-engineering platform that we recently established, called Universal Knock-in System or UKiS, to develop a human cell trio, a set of three isogenic cell lines that are homozygous for two different numbers of repeats (first and second lines) or heterozygous for the two repeat numbers (third line). As an example of a polyQ disease, we chose spinocerebellar ataxia type 2 (SCA2). In a pseudodiploid human cell line, both alleles of the glutamine-encoding triplet repeat in the SCA2-causing gene, ataxin 2 or ATXN2, were first knocked in with a donor sequence encoding both thymidine kinase and either puromycin or blasticidin resistance proteins under dual drug selection. The knocked-in donor alleles were then substituted with a payload having either 22 or 76 triplet repeats in ATXN2 by ganciclovir negative selection. The two-step substitution and subsequent SNP typing and genomic sequencing confirmed that the SCA2-modeling isogenic cell trio was obtained: three clones of 22-repeat homozygotes, two clones of 22/76-repeat heterozygotes and two clones of 76-repeat homozygotes. Finally, RT-PCR and immunoblotting using the obtained clones showed that, consistent with previous observations, glutamine tract expansion reduced transcriptional and translational expression of ATXN2. The cell clones with homozygous long-repeat alleles, which are rarely obtained from patients with SCA2, showed more drastic reduction of ATXN2 expression than the heterozygous clones. This study thus demonstrates the potential of UKiS, which is a beneficial platform for the efficient development of cell models not only for polyQ diseases but also for any other genetic diseases, which may accelerate our deeper understanding of disease mechanisms and cell-based screening for therapeutic drugs.

    DOI: 10.1266/ggs.22-00030

    PubMed

    researchmap

  • Biallelic and gene-wide genomic substitution for endogenous intron and retroelement mutagenesis in human cells. International journal

    Tomoyuki Ohno, Taichi Akase, Shunya Kono, Hikaru Kurasawa, Takuto Takashima, Shinya Kaneko, Yasunori Aizawa

    Nature communications   13 ( 1 )   4219 - 4219   2022.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Functional annotation of the vast noncoding landscape of the diploid human genome still remains a major challenge of genomic research. An efficient, scarless, biallelic, and gene-wide mutagenesis approach is needed for direct investigation of the functional significance of endogenous long introns in gene regulation. Here we establish a genome substitution platform, the Universal Knock-in System or UKiS, that meets these requirements. For proof of concept, we first used UKiS on the longest intron of TP53 in the pseudo-diploid cell line HCT116. Complete deletion of the intron, its substitution with mouse and zebrafish syntenic introns, and specific removal of retrotransposon-derived elements (retroelements) were all efficiently and accurately achieved in both alleles, revealing a suppressive role of intronic Alu elements in TP53 expression. We also used UKiS for TP53 intron deletion in human induced pluripotent stem cells without losing their stemness. Furthermore, UKiS enabled biallelic removal of all introns from three human gene loci of ~100 kb and longer to demonstrate that intron requirements for transcriptional activities vary among genes. UKiS is a standard platform with which to pursue the design of noncoding regions for genome writing in human cells.

    DOI: 10.1038/s41467-022-31982-1

    PubMed

    researchmap

  • A guideline and challenges toward the minimization of bacterial and eukaryotic genomes

    Hikaru Kurasawa, Tomoyuki Ohno, Ryusei Arai, Yasunori Aizawa

    CURRENT OPINION IN SYSTEMS BIOLOGY   24   127 - 134   2020.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.coisb.2020.10.012

    Web of Science

    researchmap

  • DNA synthesis by fragment assembly using extra-cellular DNA delivered by artificial controlled horizontal transfer. International journal

    Shinya Kaneko, Hiromi Fukushima, Misako Nakahama, Satomi Asano, Yasumasa Miyazaki, Yasunori Aizawa, Mitsuhiro Itaya

    Journal of biochemistry   163 ( 4 )   305 - 312   2018.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DNA synthesis in the Bacillus subtilis cells has become possible using extra-cellular DNA. Generally, purified DNAs in a test tube have been required to introduce into the host cells for molecular cloning technology in the laboratory. We have developed a cell lysis technique for natural transformation using stable extra-cellular plasmid DNAs, in which the extra-cellular plasmid DNAs are released from lysed Escherichia coli cells. DNA synthesis then proceeds by fragment assembly using the stable extracellular DNAs, without biochemical purification. DNA synthesis of the mouse mitochondrial genome in B. subtilis genome was illustrated using four E. coli strains with plasmid DNAs carrying contiguous DNA fragments. In the natural environment, unpurified extra-cellular DNAs contribute to the gene delivery during horizontal gene transfer (HGT). The technology introduced in the present study mimics HGT and should have a wide range of applications.

    DOI: 10.1093/jb/mvx085

    PubMed

    researchmap

  • Establishment of a genome-wide and quantitative protocol for assessment of transcriptional activity at human retrotransposon L1 antisense promoters. Reviewed

    Ishiguro K, Higashino S, Hirakawa H, Sato S, Aizawa Y

    Genes & genetic systems   92 ( 5 )   243 - 249   2018.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Long interspersed element 1 (L1) retrotransposon sequences are widespread in the human genome, occupying ~500,000 locations. The majority of L1s have lost their retrotransposition capability, although a significant population of human L1s maintains bidirectional transcriptional activity from the internal promoter. While the sense promoter drives transcription of the entire L1 mRNA and leads to L1 retrotransposition, the antisense promoter (ASP) transcribes L1-gene chimeric RNAs that include neighboring exon sequences. Activation mechanisms and functional impacts of L1ASP transcription are thought to vary at every L1ASP location. To explore the locus-specific regulation and function of L1ASP transcription, quantitative methodology is necessary for identifying the genomic positions of highly active L1ASPs on a genome-wide scale. Here, we employed deep-sequencing techniques and built a 3' RACE-based experimental and bioinformatics protocol, named the L1 antisense transcriptome protocol (LATRAP). In LATRAP, the PCR primer and the read mapping scheme were designed to reduce false positives and negatives, which may have been included as hits in previous cloning studies. LATRAP was here applied to the A549 human lung cancer cell line, and 313 L1ASP loci were detected to have transcriptional activity but differed in the number of mapped reads by four orders of magnitude. This indicates that transcriptional activities of the individual L1ASPs can vary greatly and that only a small population of L1ASP loci is active within individual nuclei. LATRAP is the first experimental method for ranking L1ASPs according to their transcriptional activity and will thus open a new avenue to unveiling the locus-specific biology of L1ASPs.

    DOI: 10.1266/ggs.16-00053

    PubMed

    researchmap

  • Transposable elements shape the human proteome landscape via formation of cis-acting upstream open reading frames. International journal

    Shohei Kitano, Hikaru Kurasawa, Yasunori Aizawa

    Genes to cells : devoted to molecular & cellular mechanisms   23 ( 4 )   274 - 284   2018.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Transposons are major drivers of mammalian genome evolution. To obtain new insights into the contribution of transposons to the regulation of protein translation, we here examined how transposons affected the genesis and function of upstream open reading frames (uORFs), which serve as cis-acting elements to regulate translation from annotated ORFs (anORFs) located downstream of the uORFs in eukaryotic mRNAs. Among 39,786 human uORFs, 3,992 had ATG trinucleotides of a transposon origin, termed "transposon-derived upstream ATGs" or TuATGs. Luciferase reporter assays suggested that many TuATGs modulate translation from anORFs. Comparisons with transposon consensus sequences revealed that most TuATGs were generated by nucleotide substitutions in non-ATG trinucleotides of integrated transposons. Among these non-ATG trinucleotides, GTG and ACG were converted into TuATGs more frequently, indicating a CpG methylation-mediated process of TuATG formation. Interestingly, it is likely that this process accelerated human-specific upstream ATG formation within transposon sequences in 5' untranslated regions after divergence between human and nonhuman primates. Methylation-mediated TuATG formation seems to be ongoing in the modern human population and could alter the expression of disease-related proteins. This study shows that transposons have potentially been shaping the human proteome landscape via cis-acting uORF creation.

    DOI: 10.1111/gtc.12567

    PubMed

    researchmap

  • Characteristics of interactions at protein segments without non-local intramolecular contacts in the Protein Data Bank. International journal

    Kota Kasahara, Shintaro Minami, Yasunori Aizawa

    PloS one   13 ( 12 )   e0205052   2018

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    The principle of three-dimensional protein structure formation is a long-standing conundrum in structural biology. A globular domain of a soluble protein is formed by a network of atomic contacts among amino acid residues, but regions without intramolecular non-local contacts are often observed in the protein structure, especially in loop, linker, and peripheral segments with secondary structures. Although these regions can play key roles for protein function as interfaces for intermolecular interactions, their nature remains unclear. Here, we termed protein segments without non-local contacts as floating segments and sought them in tens of thousands of entries in the Protein Data Bank. As a result, we found that 0.72% of residues are in floating segments. Regarding secondary structural elements, coil structures are enriched in floating segments, especially for long segments. Interactions with polypeptides and polynucleotides, but not chemical compounds, are enriched in floating segments. The amino acid preferences of floating segments are similar to those of surface residues, with exceptions; the small side chain amino acids, Gly and Ala, are preferred, and some charged side chains, Arg and His, are disfavored for floating segments compared to surface residues. Our comprehensive characterization of floating segments may provide insights into understanding protein sequence-structure-function relationships.

    DOI: 10.1371/journal.pone.0205052

    PubMed

    researchmap

  • Hypothetical gene C18orf42 encodes a novel protein kinase A-binding protein Reviewed

    Makiha Fukuda, Yasunori Aizawa

    GENES TO CELLS   20 ( 4 )   267 - 280   2015.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/gtc.12217

    Web of Science

    PubMed

    researchmap

  • Polymorphic L1 retrotransposons are frequently in strong linkage disequilibrium with neighboring SNPs Reviewed

    Saneyuki Higashino, Tomoyuki Ohno, Koichi Ishiguro, Yasunori Aizawa

    GENE   541 ( 1 )   55 - 59   2014.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.gene.2014.03.008

    Web of Science

    PubMed

    researchmap

  • A Peptide Nucleic Acid (PNA) Heteroduplex Probe Containing an Inosine-Cytosine Base Pair Discriminates a Single-Nucleotide Difference in RNA Reviewed

    Katsuhiko Matsumoto, Eiji Nakata, Tomoki Tamura, Isao Saito, Yasunori Aizawa, Takashi Morii

    CHEMISTRY-A EUROPEAN JOURNAL   19 ( 16 )   5034 - 5040   2013.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/chem.201204183

    Web of Science

    PubMed

    researchmap

  • Genes that integrate multiple adipogenic signaling pathways in human mesenchymal stem cells Reviewed

    Tomoya Ito, So Tsuruta, Koki Tomita, Kunio Kikuchi, Takahide Yokoi, Yasunori Aizawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   409 ( 4 )   786 - 791   2011.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2011.05.089

    Web of Science

    PubMed

    researchmap

  • Transcripts of unknown function in multiple-signaling pathways involved in human stem cell differentiation Reviewed

    Kunio Kikuchi, Makiha Fukuda, Tomoya Ito, Mitsuko Inoue, Takahide Yokoi, Suenori Chiku, Toutai Mitsuyama, Kiyoshi Asai, Tetsuro Hirose, Yasunori Aizawa

    NUCLEIC ACIDS RESEARCH   37 ( 15 )   4987 - 5000   2009.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/nar/gkp426

    Web of Science

    PubMed

    researchmap

  • Gene-breaking: A new paradigm for human retrotransposon-mediated gene evolution Reviewed

    SJ Wheelan, Y Aizawa, JS Han, JD Boeke

    GENOME RESEARCH   15 ( 8 )   1073 - 1078   2005.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1101/gr.3688905

    Web of Science

    researchmap

  • Dual DNA recognition codes of a short peptide derived from the basic leucine zipper protein EmBP1 Reviewed

    A Hirata, M Ueno, Y Aizawa, K Ohkubo, T Morii, S Yoshikawa

    BIOORGANIC & MEDICINAL CHEMISTRY   13 ( 9 )   3107 - 3116   2005.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bmc.2005.02.052

    Web of Science

    researchmap

  • The pathway for DNA recognition and RNA integration by a group II intron retrotransposon Reviewed

    Y Aizawa, Q Xiang, AM Lambowitz, AM Pyle

    MOLECULAR CELL   11 ( 3 )   795 - 805   2003.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/S1097-2765(03)00069-8

    Web of Science

    researchmap

  • A general strategy to determine a target DNA sequence of a short peptide: Application to a D-peptide Reviewed

    T Morii, T Tanaka, S Sato, M Hagihara, Y Aizawa, K Makino

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   124 ( 2 )   180 - 181   2002.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/ja017078f

    Web of Science

    PubMed

    researchmap

  • 短鎖ペプチドによる認識DNA塩基配列決定法の確立 Reviewed

    佐藤慎一, 田中智久, 萩原正規, 相沢康則, 森井孝, 牧野圭祐

    日本化学会第81春季年会,2002.3   2002

     More details

    Language:Japanese  

    researchmap

  • オリゴペプチド標的DNA配列の一般的決定法 Reviewed

    佐藤慎一, 田中智久, 萩原正規, 相沢康則, 森井孝, 牧野圭祐

    日本化学会第81春季年会,2F6-10,2002   2002

     More details

    Language:Japanese  

    researchmap

  • Kinetic dissection of the multistep process in L1.ltrB intron mobility

    Aizawa Y, Xiang Q, Pyle AM

    Nucleic Acids Res Suppl.   1   249 - 250   2001

     More details

    Language:English   Publishing type:Research paper (international conference proceedings)  

    researchmap

  • Stability of the dimerization domain effects the cooperative DNA binding of short peptides Reviewed

    Y Aizawa, Y Sugiura, M Ueno, Y Mori, K Imoto, K Makino, T Morii

    BIOCHEMISTRY   38 ( 13 )   4008 - 4017   1999.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/bi9828829

    Web of Science

    researchmap

  • Comparison of the sequence-selective DNA binding by peptide dimers with covalent and noncovalent dimerization domains Reviewed

    Y Aizawa, Y Sugiura, T Morii

    BIOCHEMISTRY   38 ( 5 )   1626 - 1632   1999.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/bi981743o

    Web of Science

    researchmap

  • Selective recognition of tandemly repeated DNA sequences by homo- and heterodimers of short peptides.

    Y. Aizawa, T. Morii, Y. Sugiura

    Nucleic acids symposium series   ( 37 )   311 - 312   1997

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Scopus

    PubMed

    researchmap

  • Cooperative oligomerization enhances sequence-selective DNA binding by a short peptide Reviewed

    T Morii, J Yamane, Y Aizawa, K Makino, Y Sugiura

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   118 ( 42 )   10011 - 10017   1996.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/ja953741m

    Web of Science

    researchmap

  • RNA CLEAVAGE BY C-1027 CHROMOPHORE, AN ENEDIYNE ANTITUMOR ANTIBIOTIC - HIGH SELECTIVITY TO AN ANTICODON ARM Reviewed

    R TOTSUKA, Y AIZAWA, M UESUGI, Y OKUNO, T MATSUMOTO, Y SUGIURA

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   208 ( 1 )   168 - 173   1995.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1006/bbrc.1995.1319

    Web of Science

    researchmap

▼display all

MISC

  • メガベーススケール領域のミニマム化によるヒトゲノム配列機能性の理解へ

    赤瀬太地, 赤瀬太地, 倉澤光, 倉澤光, 山根里歩, 川上惠利, 橋本陽太, 松浦優太, 堀川あゆみ, 堀川あゆみ, 山崎翔太, 金子真也, 大野智幸, 相澤康則, 相澤康則, 相澤康則

    日本分子生物学会年会プログラム・要旨集(Web)   48th   2025

  • 20Mb領域のミニマム化によるヒトゲノム配列機能性の理解へ

    赤瀬太地, 赤瀬太地, 倉澤光, 倉澤光, 山根里歩, 川上惠利, 橋本陽太, 松浦優太, 堀川あゆみ, 堀川あゆみ, 山崎翔太, 金子真也, 大野智幸, 相澤康則, 相澤康則, 相澤康則

    日本遺伝学会大会プログラム要旨集(CD-ROM)   97th   2025

  • ヒトX染色体上にある細胞生存に必須なゲノム領域を探索する方法

    赤瀬太地, 赤瀬太地, 倉澤光, 橋本陽太, 松浦優太, 山崎翔太, 金子真也, 大野知幸, 相澤康則, 相澤康則, 相澤康則

    日本分子生物学会年会プログラム・要旨集(Web)   47th   2024

  • Basic and clinical studies on functional RNA molecules for advanced medical technologies Reviewed

    Toshihiro Takizawa, Akihiko Gemma, Kumiko Ui-Tei, Yasunori Aizawa, Yoel Sadovsky, John M. Robinson, Masahiro Seike, Koichi Miyake

    Journal of Nippon Medical School   77 ( 2 )   71 - 79   2010.4

     More details

    Language:English   Publishing type:Book review, literature introduction, etc.  

    DOI: 10.1272/jnms.77.71

    Scopus

    PubMed

    researchmap

  • RNAとゲノム(最近の話題) 高次生命現象を支える機能性RNA--短いRNAと長いRNA

    相澤 康則, 辻本 豪三, 寺澤 和哉

    ゲノム医学   7 ( 1 )   67 - 70,5   2007.2

     More details

    Language:Japanese   Publisher:メディカルレビュー社  

    CiNii Books

    researchmap

  • ”非共有結合ペプチド二量体による特異的DNA塩基配列認識機構” Reviewed

    相澤康則, 杉浦幸雄, 牧野圭祐, 森井 孝

    日本化学会第76春季年会予稿集(1999).   1999

     More details

    Language:Japanese  

    researchmap

  • Arranging Functional Quarternary Structures of DNA Binding Peptides (BIOORGANIC CHEMISTRY-Bioactive Chemistry)

    Morii Takashi, Aizawa Yasunori, Sugiura Yukio

    ICR annual report   4   40 - 41   1998.3

     More details

    Language:English   Publisher:Institute for Chemical Research, Kyoto University  

    CiNii Books

    researchmap

  • ”Cooperative DNA Binding by Short Peptides.” Reviewed

    相沢康則, 森井孝, 杉浦幸雄

    第25回核酸化学シンポジウム予稿集(1998).   1998

     More details

    Language:Japanese  

    researchmap

▼display all

Presentations

  • The Dark Matter of the HUman Genome Invited

    Aizawa Yasunori

    2015.2 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    researchmap

  • De novo functional characterization of upstream ORFs in mammals Invited

    Aizawa Yasunori

    2015.6 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    researchmap

  • Hidden functional peptides in the Dark Matter of the human genome Invited International conference

    Aizawa Yasunori

    Asian Three Roundtable on Nucleic Acids  2014.10 

     More details

    Language:English  

    researchmap

  • ヒト・タンパク質遺伝子「候補」の機能解析

    相澤 康則

    日本遺伝学会 第86回大会  2014.9 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

    researchmap

  • A mammalian intergenic ORF encodes an unconventional activator of ion channels International conference

    Aizawa Yasunori

    Cold Spring Harbor Laboratory Meeting: Translational Control  2014.9 

     More details

    Language:English   Presentation type:Poster presentation  

    researchmap

  • Functionality of short ORFs in mammalian cells Invited

    Aizawa Yasunori

    2014.6 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    researchmap

  • Toward Minimization of 1% portion of the Human Genome

    Hikaru Kurasawa, Taichi Akase, Hinata Hashimoto, Yuta Matsuura, Riho Yamane, Shota Yamazaki, Shinya Kaneko, Tomoyuki Ohno, Yasunori Aizawa

    2024.10 

     More details

    Language:English   Presentation type:Poster presentation  

    researchmap

  • Defining the minimal set of genes for autotrophy in Cupriavidus necator H16 and prospects for synthetic autotroph.

    Shota Yamazaki, Yuriko Hori, Yasunori Aizawa

    2024.10 

     More details

    Language:English   Presentation type:Poster presentation  

    researchmap

  • Large-scale human genome engineering for basic science & therapy. Invited

    2024.11 

     More details

    Language:English   Presentation type:Oral presentation (invited, special)  

    researchmap

  • Understanding human genome architecture via genome minimization on X chromosome.

    2024.9 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

    researchmap

  • 広いゲノム領域の細胞生存必須性を評価する方法の開発

    倉澤光, 赤瀬太地, 橋本陽太, 松浦優太, 山﨑翔太, 金子真也, 大野智幸, 相澤康則

    日本遺伝学会第96回大会(高知工科大学)  2024.9 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

    researchmap

  • Transcriptional dynamics of L1 antisense promoters during differentiation of human iPS cells into β-cells. Transposable elements

    Hinata Hashimoto, Kengo Matsuzawa, Nobuaki Shiraki, Yasunori Aizawa

    2024.10 

     More details

    Language:Japanese   Presentation type:Poster presentation  

    researchmap

  • ヒトiPS細胞に対する大規模ゲノムエンジニアリング Invited

    相澤康則

    殿町・羽田再生医療拠点キックオフシンポジウム(Shimadzu Tokyo Innovation Plaza)  2024.9 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    researchmap

  • ヒトuORF由来タンパク質の細胞内安定性を決定する要因の探究

    橋本陽太, 赤瀬太地, 相澤康則

    日本遺伝学会第96回大会(高知工科大学)  2024.9 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

    researchmap

  • TP53第1イントロン内レトロトランスポゾンAluが転写発現を抑制する機序を解明する

    山本歩夢, 大野知幸, 赤瀬太地, 相澤康則

    日本遺伝学会第96回大会(高知工科大学)  2024.9 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

    researchmap

  • ヒト培養細胞におけるDNMTの必須性

    松本篤樹, 伊志嶺桃佳, 赤瀬太地, 相澤康則

    日本遺伝学会第96回大会(高知工科大学)  2024.9 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

    researchmap

  • 大規模ゲノム構築によるゲノム機能研究 Invited

    相澤康則

    第122回醗酵学談話会(アサヒビール株式会社吹田工場)  2024.8 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    researchmap

  • Large-Scale Genome Downsizing in Human Induced Pluripotent Stem Cells.

    2024.8 

     More details

    Language:English   Presentation type:Poster presentation  

    researchmap

  • 独立栄養条件下で高発現する水素酸化細菌遺伝子の機能解析

    山崎翔太, 相澤康則

    日本遺伝学会第96回大会(高知工科大学)  2024.9 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

    researchmap

  • 枯草菌を用いたGap Repair Cloning法

    金子真也, 相澤康則

    令和6年度グラム陽性菌ゲノム機能会議(長野市若里市民文化ホール)  2024.8 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

    researchmap

  • ゲノム「読む」から「書く」 Invited

    相澤康則

     More details

    Presentation type:Media coverage  

    researchmap

  • 高校1年生の時に芽生えたバイオへの三つ子の魂 〜ゲノム構築への道 Invited

    相澤康則

    大学講演セミナー(八王子学園八王子高校)  2024.7 

     More details

    Language:Japanese  

    researchmap

  • ヒトゲノム構築の技術開発とその応用 Invited

    相澤康則

    第3回生物機能化学国際シンポジウム  2024.6 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    researchmap

  • Large-scale human genome engineering for basic science and therapy. Invited

    2025.2 

     More details

    Language:English   Presentation type:Oral presentation (invited, special)  

    researchmap

  • 上流ORFにコードされたMicroproteinの細胞内安定性評価

    橋本陽太, 赤瀬太地, 相澤康則

    第47回日本分子生物学会年会(福岡国際会議場マリンメッセ福岡)  2024.11 

     More details

    Language:Japanese   Presentation type:Poster presentation  

    researchmap

  • 大規模ゲノム構築技術によるゲノム機能探究とその産業展開 Invited

    相澤康則

    福岡大学理学研究科FD講演会  2025.2 

     More details

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    researchmap

  • “技術覚醒“ヒト細胞ゲノム工学技術の最前線 Invited

    相澤康則

    RINKフェスティバル2025(TIAT SKY HALL;羽田空港)  2025.2 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    researchmap

  • 水素酸化細菌の従属栄養・独立栄養スイッチングに必要な遺伝子セットの理解

    山崎翔太, 相澤康則

    第47回日本分子生物学会年会(福岡国際会議場マリンメッセ福岡)  2024.11 

     More details

    Language:Japanese   Presentation type:Poster presentation  

    researchmap

  • ヒトX染色体上にある細胞生存に必須なゲノム領域を探索する方法

    赤瀬 太地, 倉澤 光, 橋本 陽太, 松浦 優太, 山﨑 翔太, 金子 真也, 大野 知幸, 相澤 康則

    第47回日本分子生物学会年会(福岡国際会議場マリンメッセ福岡)  2024.11 

     More details

    Language:Japanese   Presentation type:Poster presentation  

    researchmap

  • 枯草菌でのGap Repair Cloning 法の開発

    金子真也, 相澤康則

    第47回日本分子生物学会年会(福岡国際会議場マリンメッセ福岡)  2024.11 

     More details

    Language:Japanese   Presentation type:Poster presentation  

    researchmap

  • イントロンに存在するレトロトランスポゾンAluの転写抑制能を検証する

    山本歩夢, 大野知幸, 赤瀬太地, 相澤康則

    第47回日本分子生物学会年会(福岡国際会議場マリンメッセ福岡)  2024.11 

     More details

    Language:Japanese   Presentation type:Poster presentation  

    researchmap

▼display all

Research Projects

  • 「次世代合成生物基盤」プロジェクト

    2023.4 - 2027.3

    神奈川県立産業技術総合研究所  有望シーズ展開事業 

      More details

    Authorship:Principal investigator 

    researchmap

  • 先端的植物バイオものづくり基盤の構築

    2023 - 2027

    科学技術振興機構  戦略的な研究開発の推進 革新的GX技術創出事業 GteX 

    大熊 盛也

      More details

    従来のバイオものづくりの原料は農業で生産される糖などのバイオマスであり、直接的なCO2削減に寄与せず、食料との競合等の問題がある。また、大腸菌や酵母等の汎用微生物が用いられ、代謝上の制約により生産化合物の種類は限定されている。そこで、植物を中心とした多様な代謝能を活用し、植物や微細藻類、新規CO2固定微生物を宿主としたCO2を直接的な原料とする工業的な方法でのものづくりのための革新的な基盤を構築する。
    植物や新規微生物の生物情報を収集し、開発途上の植物・微細藻類において、代謝デザイン、人工的なゲノム構築やゲノム大規模改変、遺伝子導入、分化制御等の先端的技術開発を実施する。これらの技術を微細藻類や培養細胞、工業化に近い植物に適用しつつ、これまで困難であった物質への生産拡大と生産性向上に取り組む。

    researchmap

    J-GLOBAL

  • 二酸化炭素資化独立栄養水素酸化細菌を用いた共重合ポリヒドロキシアルカン酸合成技術の開発

    2022 - 2025

    科学技術振興機構  産学が連携した研究開発成果の展開 研究成果展開事業 研究成果最適展開支援プログラム(A-STEP) 産学共同(本格型) 

    柘植 丈治

      More details

    ゲノム編集された独立栄養水素酸化細菌により、二酸化炭素と水素を原料として特定の共重合成分を導入した高純度・高品質の新規共重合型ポリヒドロキシアルカン酸(PHA)を、安全かつ高い生産性で、より大きなスケールで製造する一貫生物合成技術を確立する。この技術により、カーボンニュートラルに寄与し、来るべき水素社会にも親和性が高く、さらに海洋プラスチックごみ問題の解決にもつながる、実用安定性と海洋生分解性を兼ね備えた革新的な海洋生分解性プラスチックを提供する。

    researchmap

    J-GLOBAL

  • ゲノムスケールのDNA設計・合成による細胞制御技術の創出

    2018 - 2025

    戦略的な研究開発の推進 戦略的創造研究推進事業 CREST 

    塩見 春彦

      More details

    本研究領域はゲノムの構造と機能に関する基本原理(ゲノムの動作原理)の解明とその知見に基づく細胞利用の基盤技術の創出を目指すものです。特に、長鎖DNAの活用を通して細胞の制御を目指すことで生命科学、ゲノム科学、細胞工学などのライフサイエンスのフロンティアの開拓と技術基盤の確立を目指します。 近年、世界的に長鎖DNAを活用した研究開発が加速しています。これらはいずれも合成生物学の流れを汲むものであり、米国、中国、英国では複数の拠点が形成され、基礎研究や技術開発、ベンチャー企業の育成など戦略的な投資が行われています。しかしながら、各国の取り組みを見ると、細胞を任意に制御するためのゲノムの設計指針にまで踏み込んだ研究開発は少ないように見受けられます。 そこで、本研究領域では将来的なゲノム設計の基盤技術の構築に向けゲノムの動作原理の解明を目的とした研究開発に取り組みます。ここでは、進展が著しい長鎖DNAの活用を視野に「ゲノムの構造と機能の解明」、「ゲノム設計のための基盤技術」、「ゲノムスケールのDNA合成技術」、「人工細胞の構築」の4つの課題を推進し、ゲノムの複雑な機能と構造に関する知見の創出とゲノム合成や人工細胞に関する新たな技術の構築を目指します。

    researchmap

    J-GLOBAL

  • Screening for functional protein-encoding ORFs located outside coding regions in the human genome

    Grant number:16K15116  2016.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    Aizawa Yasunori, TAKAO KEIZO, TAGUCHI HIDEKI, YAMASHITA HITOYOSHI, SASAKI HIROTAKA, KURASAWA HIKARU

      More details

    Grant amount:\3640000 ( Direct Cost: \2800000 、 Indirect Cost:\840000 )

    This study identified a novel candidate of small ORFs (uORF13) that is located within untranslated regions of human messenger RNAs and encodes functional proteins. The uORF13-encoding protein (uORF13p) is localized at mitochondria and seems to be involved in regulation of the membrane potential. Alanine-scanning mutagenesis allowed us to find two different peptide motifs, which can have opposite roles in the membrane potential control. In addition to our first example of functional protein-encoding small ORF located in noncoding regions, this finding also supports that the human genome encodes more functional proteins which we have yet to discover.

    researchmap

  • ドメイン構造をもたない天然変性タンパク質群に対する構造機能相関解析

    Grant number:24113706  2012.4 - 2014.3

    日本学術振興会  科学研究費助成事業  新学術領域研究(研究領域提案型)

    相澤 康則

      More details

    Grant amount:\11830000 ( Direct Cost: \9100000 、 Indirect Cost:\2730000 )

    天然変性タンパク質での構造機能相関性を理解するためには、ドメイン構造をもたない、全長にわたって天然変性なタンパク質(以下、全長IDP)を研究対象とする必要性がある。本研究課題では細胞内で機能を発揮する新規全長IDPの同定と、その機能発現メカニズムの解明を研究目的とした。本年度は3種類の新規全長IDPの機能解析に大きな進展があった。これら全ての研究成果は現在論文投稿中あるいは発表準備である。
    昨年度までにイオンチャネルを活性化させることが明らかになっていた膜貫通型IDP(以下IDP1)の作用機序が本年度の研究で明らかになった。これまで知られているイオンチャネル活性化機構のいずれとも異なる、新しい分子機構であった。2つめの全長IDPは、4種類あるプロテインキナーゼA(PKA)ホモログのうち、2種類に選択的に結合し、これらPKAを細胞形質膜に効率よく輸送、局在させることを我々は見いだした。3つめの全長IDPは、ノンコーディングゲノム領域、すなわち現在の遺伝子学に照らし合わせると遺伝子は存在しないと考えられているゲノム領域から同定された。このIDPは、IDP1と同様に膜貫通型IDPであり、小胞体機能に関与することなどが明らかになっている。以上、新たに同定されたこれら全長IDPはそれぞれ、異なる細胞内シグナル伝達経路を調節している。この結果は、細胞内シグナル伝達における分子機構を理解する上で、「鍵と鍵穴」を例にこれまで考えられてきた、劇的な構造変化を伴わないタンパク質間相互作用だけではなく、ドメインをもたない全長IDP間の相互作用原理を解き明かす重要性を強く示しているといえる。
    また、全長IDPの細胞内安定に関する新しい知見も得た。現在、IDPはプロテアソーム分解系にその細胞内寿命を支配されていると考えられているが、この概念に反する実験結果を得ている。これも現在公表準備中である。

    researchmap

  • ドメイン構造をもたない天然変性タンパク質群における構造機能相関解析

    Grant number:22113505  2010 - 2011

    日本学術振興会  科学研究費助成事業  新学術領域研究(研究領域提案型)

    相澤 康則

      More details

    Grant amount:\11700000 ( Direct Cost: \9000000 、 Indirect Cost:\2700000 )

    本研究では、天然変性タンパク質での「配列-構造-機能の対応関係」を追究するために、部分的にもドメイン構造を取り得ない、すなわちタンパク質全体が生理的条件下でランダムコイル状態にある"完全"天然変性タンパク質(NEDP(Naturally and Entirely Denatured protein))に対象を絞って、構造機能解析を進めた。23年度の構造解析として、22年度にクローニングした7種類の新規NEDP候補の二次構造を評価し、予想通り全長にわたって天然変性であるかどうかを検証した。具体的には、大腸菌内で組換えタンパク質としてタグ付き発現させた後、アフィニティーカラムで精製し、円二色分散計およびNMR(HSQC解析)を用いて二次構造を評価した。その結果、4種類のNEDPが生理的溶液条件下で全長にわたって天然変性であることが分かった。そこで次にこれら4種類の新規NEDPが細胞内で相互作用するタンパク質の同定を目指した。具体的には、各NEDPコード配列のN末端およびC末端に各種タグ配列が融合したタンパク質をヒト培養細胞内で発現させ、タグに対する抗体で免疫沈降後、質量分析を行った。得られた質量分析の結果をもとに変異体解析を進めたところ、主要な細胞内シグナル伝達の活性化制御に関わっているNEDPと、ミトコンドリア機能に関与するNEDPをそれぞれ発見することができた。本研究により、ドメインを持たないタンパク質の機能発現を研究する上で格好の事例を提示することができた。さらに上記とは別に新規NEDP候補42種類を、ヒトゲノムのヒトコーディング領域からクローニングし、機能性NEDPのさらなる探索のリソース構築を行った。

    researchmap

  • ヒトレトロポゾンL1タンバク質と宿主細胞機能とのクロストーク

    Grant number:18710167  2006 - 2007

    日本学術振興会  科学研究費助成事業  若手研究(B)

    相澤 康則

      More details

    Grant amount:\3500000 ( Direct Cost: \3500000 )

    本研究計画実施前の予備実験から、ORF1pの過剰発現がヒト細胞(Hela)で宿主遺伝子の1つ、インターロイキン8(以下、IL8)の細胞内mRNA量を上昇させることが分かっていた。そこで本研究プロジェクトでは、ヒトレトロトランスポソンL1にコードされているタンパク質のひとつ、ORF1pの細胞機能の同定を目指した。
    平成18年度の研究により、ORF1pはIL8のプロモーター活性を上昇させないことがルシフェラーゼ・レポーターアッセイから明らかになっている。そこで平成19年度は、IL8遺伝子の3'UTRをルシフェラーゼ下流に挿入したレポータープラスミドを用いて、ORF1pによるIL8 mRNA安定化の可能性を検討した。これまでのところ、IL8 3'UTR においてORF1p過剰発現によるレポーターmRNAの安定化に寄与している配列部位は同定されなかった。以上の結果から、ORF1pによる内在性IL8遺伝子の発現上昇は、一般的に見られる転写開始あるいはmRNA安定化によるものではなく、例外的な分子メカニズムによって誘発されていることが強く示唆された。そこで、クロマチン構造との関連性を調べるために、レポータープラスミドを染色体に組み込んだ細胞株を作成した。
    さらに本年度は、ORF1pの機能を解明することを最終目的として、ORF1pと細胞内で結合するタンパク質を同定するために、ORF1pにFLAGタグをつけた融合タンパク質を発現するプラスミドの作成を行った。

    researchmap

▼display all