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Development of programmable small molecules capable of switching ON the transcriptional machinery of pluripotency genes.

Research Project

Project/Area Number 24710261
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Chemical biology
Research InstitutionKyoto University

Principal Investigator

NAMASIVAYAM Ganesh Pandian  京都大学, 物質-細胞統合システム拠点, 特定拠点助教 (20625446)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Hiroshi  京都大学, 理学研究科, 教授 (50183843)
BANDO Toshikazu  京都大学, 理学研究科, 准教授 (20345284)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords人工遺伝子スイッチ / 細胞リプログラミング / 小分子 / 合成生物学 / iPS細胞 / 人口遺伝子スイッチ
Research Abstract

Artificial transcriptional activators with epigenetic activity can retain the capability of their natural equivalents to rewire transcriptional machinery within a cell. During this tenure, we have demonstrated the potential of our novel small molecules for genome engineering termed `SAHA-PIP` containing sequence-specific pyrrole-imidazole polyamides (PIPs) and SAHA, a histone deacetylase inhibitor. We tailored SAHA-PIPs to distinctively activate the pluripotency genes by triggering transcriptionally permissive chromatin in mouse fibroblasts. We have generated PIP conjugates with fluorescent dyes and those targeting different epigenetic enzymes. In human fibroblasts, a SAHA-PIP got characterized as germ cell gene switch and genome-wide gene analysis revealed the capability of thirty-two distinct small molecules to trigger the transcriptional activation of exclusive developmental genes. Our results contribute to the development of novel chemical approach for controlling cell fate.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (40 results)

All 2014 2013 2012 Other

All Journal Article (15 results) (of which Peer Reviewed: 4 results) Presentation (8 results) Book (1 results) Remarks (16 results)

  • [Journal Article] Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts2014

    • Author(s)
      Ganesh N. Pandian et al.
    • Journal Title

      Sci. Rep

      Volume: 4

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cellular reprogramming for pancreatic beta cell regeneration : clinical potential of small molecule control2014

    • Author(s)
      Ganesh N. Pandian et al.
    • Journal Title

      Clin. Transl. Med

      Volume: 3 Pages: 6-6

    • Related Report
      2013 Final Research Report
  • [Journal Article] Distinct DNA-based epigenetic switches trigger differential transcriptional activation in human dermal fibroblasts2014

    • Author(s)
      Pandian GN, Nagase H
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 3843-3843

    • DOI

      10.1038/srep03843

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A synthetic small molecule for targeted transcriptional activation of germ cell genes in a human somatic cell2013

    • Author(s)
      L. Han, Ganesh N. Pandian et al.
    • Journal Title

      Angew. Chem. Int. Ed., HOT PAPER

      Volume: 125 Pages: 13652-13655

    • Related Report
      2013 Final Research Report
  • [Journal Article] Pandian et al., Clinical-Grade iPS Cells : Need For versatile small molecules and optimal cell sources2013

    • Author(s)
      Y-L. Wu, Ganesh N. Pandian et al.
    • Journal Title

      Chem. Biol

      Volume: 20 Pages: 1311-1322

    • Related Report
      2013 Final Research Report
  • [Journal Article] Chemically induced pluripotent stem cells (CiPSCs) : A transgene-free approach2013

    • Author(s)
      S. Masuda, J. Wu, T. Hishida, Ganesh N. Pandian, et al.
    • Journal Title

      J. Mol. Cell Biol

      Volume: 5 Pages: 354-355

    • Related Report
      2013 Final Research Report
  • [Journal Article] Design of a new fluorescent probe : Pyrrole/Imidazole hairpin polyamides with pyrene conjugation at theirγ-turn2013

    • Author(s)
      T. Vaijayanthi, T. Bando, K. Hashiya, Ganesh N. Pandian, et al.
    • Journal Title

      Bioorg. Med. Chem

      Volume: 21 Pages: 852-855

    • NAID

      120005241442

    • Related Report
      2013 Final Research Report
  • [Journal Article] Strategies to modulate heritable epigenetic defects in cellular machinery : Lessons from nature2013

    • Author(s)
      Ganesh N Pandian and H. Sugiyama
    • Journal Title

      Pharmaceuticals

      Volume: 6 Pages: 1-24

    • NAID

      120005241367

    • Related Report
      2013 Final Research Report
  • [Journal Article] Synthesis and biological evaluation of a targeted DNA-binding transcriptional activator with HDAC8 inhibitory activity2013

    • Author(s)
      A. Saha, Ganesh N Pandian et al.
    • Journal Title

      Bioorg. Med. Chem

      Volume: 21 Pages: 4201-4209

    • Related Report
      2013 Final Research Report
  • [Journal Article] A Synthetic Small Molecule Enforces Targeted Transcriptional Activation of Germ Cell Genes in a Human Somatic Cell.2013

    • Author(s)
      Han L, Pandian GN, Junetha S, Sato S, Anandhakumar C, Taniguchi J, Saha A, Bando T, Nagase H and Sugiyama H.
    • Journal Title

      Angewandte Chemie

      Volume: 52 Issue: 50 Pages: 13410-13413

    • DOI

      10.1002/anie.201306766

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Strategies to Tinker with Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature2013

    • Author(s)
      Pandian, G. N.; Sugiyama, H.
    • Journal Title

      Pharmaceuticals

      Volume: 6 Issue: 1 Pages: 1-24

    • DOI

      10.3390/ph6010001

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A synthetic small molecule for rapid induction of multiple pluripotency genes in mouse embryonic fibroblast2012

    • Author(s)
      Ganesh N Pandian et al.
    • Journal Title

      Sci. Rep

      Volume: 2

    • Related Report
      2013 Final Research Report
  • [Journal Article] Progress and prospects of pyrrole-imidazole polyamide-fluorophore conjugate as sequence-selective DNA probes2012

    • Author(s)
      T. Vaijayanthi, T. Bando, Ganesh N. Pandian et al.
    • Journal Title

      ChemBioChem

      Volume: 13 Pages: 2170-2185

    • Related Report
      2013 Final Research Report
  • [Journal Article] Development of programmable small DNA-binding molecules with epigenetic activity for induction of core pluripotency genes, Bioorg2012

    • Author(s)
      Ganesh N. Pandian et al.
    • Journal Title

      Med. Chem

      Volume: 20 Pages: 2656-2660

    • Related Report
      2013 Final Research Report
  • [Journal Article] A synthetic small molecule for rapid induction of multiple pluripotency genes in mouse embryonic fibroblasts2012

    • Author(s)
      Pandian GN, Nakano Y, Sato S, Morinaga H, Bando T, Nagase H, Sugiyama H
    • Journal Title

      Sci Rep

      Volume: 2:544 Issue: 1 Pages: 544-544

    • DOI

      10.1038/srep00544

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Synthetic small molecules to distinctively trigger transcriptional activation of pluripotency and germ-cell genes in a somatic cell2014

    • Author(s)
      Ganesh N. Pandian et al.
    • Organizer
      Poster presentation in iPS cells in drug discovery and development/ CiRA international symposium
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] DNA-based Epigenetic Switches to Control Cell Fate2013

    • Author(s)
      Ganesh N. Pandian et al.
    • Organizer
      Poster presentation in 40th International Symposium on Nucleic Acid Chemistry
    • Place of Presentation
      Yokohama, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Novel chemical approach for cellular reprograming2013

    • Author(s)
      Ganesh N. Pandian et al.
    • Organizer
      Oral presentation in 8th Annual Meeting of the Japanese Society for Chemical Biology
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Targeting small molecules as transcriptional activators for selective induction of pluripotency genes in somatic fibroblasts2013

    • Author(s)
      Ganesh N. Pandian et al.
    • Organizer
      Won Biomater ials Science Poster Award (First Prize) in RSC-iCeMS Joint International Symposium : Cell-Material Integration and Biomaterials Science
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] DNA-based Epigenetic Switches to Control Cell Fate2013

    • Author(s)
      Ganesh N. Pandian
    • Organizer
      40th International Symposium on Nucleic Acid Chemistry
    • Place of Presentation
      Yokohama, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Artificial epigenetic switches to selectively reprogram the transcriptional machinery conferring to cell fate2012

    • Author(s)
      Ganesh N. Pandian et al.
    • Organizer
      World Stem Cell Summit2012
    • Place of Presentation
      Palm Beach, FL, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Synthetic genetic switches for selective induction of pluripotency in mouse and human fibroblasts2012

    • Author(s)
      Ganesh N. Pandian et al.
    • Organizer
      SPO TLIGHT TALK and won CROSS - DISCIPLINARY RESEARCH PRIZE at 4th annual symposium of Institute for integrated cell-material sciences (iCeMS)
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Artificial epigenetic switches to selectively reprogram the transcriptional machinery conferring to cell fate2012

    • Author(s)
      Ganesh N Pandian
    • Organizer
      World Stem Cell Summit
    • Place of Presentation
      West Palm Beach, Florida (USA)
    • Related Report
      2012 Research-status Report
  • [Book] Targeted editing of therapeutic genes using DNA-based transcriptional activators: Scope and challenges in Chemical Biology of Nucleic Acids: Fundamentals and Clinical Applications ed. by Volker A. Erdmann, Wojciech T. Markiewicz, and Jan Barciszewski REFEREED2014

    • Author(s)
      Ganesh N Pandian and H. Sugiyama
    • Related Report
      2013 Final Research Report
  • [Remarks] Ganesh N. Pandian, Induced pluripotent stem cells and Genetic switches, Stem Cell Research Laboratory, Government Stanley Hospital, Tamil Nadu, India, 21 Sep. 2013

    • Related Report
      2013 Final Research Report
  • [Remarks] Ganesh N. Pandian, Cellular reprogramming–A chemical approach, Madurai Kamraj University, Tamil Nadu, India, 18 Sep. 2013

    • Related Report
      2013 Final Research Report
  • [Remarks] Ganesh N. Pandian, Cellular time machine : Back to the future, Kalasalingam University, Tamil Nadu, India, 17 Sep. 2013

    • Related Report
      2013 Final Research Report
  • [Remarks] Ganesh N. Pandian, Genetic switches to control cellular time machine, Lady Doak College, Tamil Nadu, India, 13 Sep. 2013

    • Related Report
      2013 Final Research Report
  • [Remarks] 日刊工業新聞「京大、"人工スイッチ"開発−細胞の遺伝子発現を制御」(2014年2月3日17面)

    • Related Report
      2013 Final Research Report
  • [Remarks] GEN News「遺伝子発現スイッチ、眠ったDNAの目覚ましに」(2014年1月31日[ウェブ])

    • Related Report
      2013 Final Research Report
  • [Remarks] マイナビニュース| Yahoo!Japanニュース「京大、狙ったDNAに結合する化合物で細胞の遺伝子発現の制御に成功」(2014年1月28日)

    • Related Report
      2013 Final Research Report
  • [Remarks] nano.com「iCeMS研究者ら、DNAに基づく化合物を作製、細胞の遺伝子発現コントロール」(2014年1月27日[ウェブ])•朝日新聞「遺伝子のスイッチ、直接入れることに成功京大グループ」(2014年1月25日8面)

    • Related Report
      2013 Final Research Report
  • [Remarks] 中日新聞「遺伝子使わずiPSか、京大、化合物加え似た細胞」(2014年1月25日3面)

    • Related Report
      2013 Final Research Report
  • [Remarks] 京都新聞「狙った遺伝子制御、京大グループ成功」(2014年1月25日28面)

    • Related Report
      2013 Final Research Report
  • [Remarks] 日本経済新聞「眠れる遺伝子働かせる、京大が化合物、iPS応用も。」(2014年1月25日42面)

    • Related Report
      2013 Final Research Report
  • [Remarks] 産経新聞「皮膚に化合物加えiPSに似た細胞京大チーム作製」(2014年1月25日28面)

    • Related Report
      2013 Final Research Report
  • [Remarks] 読売新聞「特定遺伝子スイッチON、化合物で活性」(2014年1月25日34面)

    • Related Report
      2013 Final Research Report
  • [Remarks] 47 News「皮膚に化合物加えiPSに似た細胞京大チーム作製」(2014年1月24日)

    • Related Report
      2013 Final Research Report
  • [Remarks] iCeMS ホームページ

    • URL

      http://www.icems.kyoto-u.ac.jp/j/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 京都大学 理学研究科 化学専攻 杉山研究室 ホームページ

    • URL

      http://kuchem.kyoto-u.ac.jp/chembio/

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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