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2021 年度 実施状況報告書

Development of a patient-personalized synapse proteomics technology for advancing precision diagnosis of mental disorders.

研究課題

研究課題/領域番号 21K07554
研究機関沖縄科学技術大学院大学

研究代表者

TAOUFIQ Zacharie  沖縄科学技術大学院大学, 細胞分子シナプス機能ユニット, スタッフサイエンティスト (10549348)

研究期間 (年度) 2021-04-01 – 2024-03-31
キーワードiPSC-derived neurons / Synapse / proteomics / psychiatry / Schizophrenia / diagnosis / biomarkers
研究実績の概要

Brain sampling on living psychiatric patient is key but unethical. Here, we have developed a way to perform: a noninvasive/harmless dissection of brain synapses from living psychiatric patients. We combined stem cell reprogramming technology and our powerful UD proteomics approach (Taoufiq et al PNAS 2020). We called this new technology: ‘Personalized Synapse Proteomics’ (PSP). In this year, we validated the concept of a PSP. The primary endpoint was to determine whether we could see alterations of brain synaptic proteins from a living psychiatric patient versus his healthy sibling. 1 we successfully generated iPS cells from blood sample of a local patient suffering from schizophrenia and his healthy sibling. 2 we successfully differentiated of the cells into neurons. 3 we managed to purify enough intact synapses from patient-derived neurons. 4 Using UD proteomics, we could have identified and quantified proteome alterations in brain synapses from a living patient with schizophrenia versus his healthy sibling. These included known schizophrenia disease biomarkers and may encompass dozens of novel and previously invisible ones. Therefore, we concluded that PSP technology prototype worked as predicted. We also filed a patent on a new culture medium recipe that makes psychiatric patients neurons much healthier and more connected.

現在までの達成度 (区分)
現在までの達成度 (区分)

1: 当初の計画以上に進展している

理由

We already validated the concept and protocol of PSP.
We have now yet to perform the final step which is to use PSP on all the patient samples.

今後の研究の推進方策

We have now performing the final step which is to compare synaptic proteomics of all other patient samples.
We have in total 4 patients for this project,
However we will use PSP on samples received from another funding source.

次年度使用額が生じた理由

Reduced activity due to Corona period (shipment delays of products).

  • 研究成果

    (4件)

すべて 2022 2021

すべて 雑誌論文 (1件) (うち国際共著 1件、 査読あり 1件、 オープンアクセス 1件) 学会発表 (2件) (うち国際学会 2件) 産業財産権 (1件)

  • [雑誌論文] Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer's disease synapse model2022

    • 著者名/発表者名
      Tetsuya Hori, Kohgaku Eguchi, Han-Ying Wang, Tomohiro Miyasaka, Laurent Guillaud, Zacharie Taoufiq, Satyajit Mahapatra, Hiroshi Yamada, Kohji Takei, Tomoyuki Takahashi
    • 雑誌名

      Elife

      巻: e73542 ページ: 1, 20

    • DOI

      10.7554/eLife.73542.

    • 査読あり / オープンアクセス / 国際共著
  • [学会発表] Molecular anatomy of brain synapses from living psychiatric patients.2021

    • 著者名/発表者名
      Zacharie Taoufiq
    • 学会等名
      NIPS Synapse Research meeting, シナプスの理解深化からの神経回路動態の再考
    • 国際学会
  • [学会発表] Molecular anatomy of brain synapses from living psychiatric patients’2021

    • 著者名/発表者名
      Zacharie Taoufiq
    • 学会等名
      OIST-RIKEN Joint Symposium, Kinds of Minds -What is thinking?-
    • 国際学会
  • [産業財産権] Proteomics-based receptor-ligand matching for optimizing human iPS cell reprogramming2021

    • 発明者名
      Taoufiq Z et al
    • 権利者名
      OIST
    • 産業財産権種類
      特許
    • 産業財産権番号
      2021-194719

URL: 

公開日: 2023-12-25  

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