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2021 Fiscal Year Research-status Report

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

Research Project

Project/Area Number 21K07554
Research InstitutionOkinawa Institute of Science and Technology Graduate University

Principal Investigator

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)

Project Period (FY) 2021-04-01 – 2024-03-31
KeywordsiPSC-derived neurons / Synapse / proteomics / psychiatry / Schizophrenia / diagnosis / biomarkers
Outline of Annual Research Achievements

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.

Current Status of Research Progress
Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

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.

Strategy for Future Research Activity

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.

Causes of Carryover

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

  • Research Products

    (4 results)

All 2022 2021

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 2 results) Patent(Industrial Property Rights) (1 results)

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

    • Author(s)
      Tetsuya Hori, Kohgaku Eguchi, Han-Ying Wang, Tomohiro Miyasaka, Laurent Guillaud, Zacharie Taoufiq, Satyajit Mahapatra, Hiroshi Yamada, Kohji Takei, Tomoyuki Takahashi
    • Journal Title

      Elife

      Volume: e73542 Pages: 1, 20

    • DOI

      10.7554/eLife.73542.

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Molecular anatomy of brain synapses from living psychiatric patients.2021

    • Author(s)
      Zacharie Taoufiq
    • Organizer
      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
    • Int'l Joint Research
  • [Presentation] Molecular anatomy of brain synapses from living psychiatric patients’2021

    • Author(s)
      Zacharie Taoufiq
    • Organizer
      OIST-RIKEN Joint Symposium, Kinds of Minds -What is thinking?-
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] Proteomics-based receptor-ligand matching for optimizing human iPS cell reprogramming2021

    • Inventor(s)
      Taoufiq Z et al
    • Industrial Property Rights Holder
      OIST
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-194719

URL: 

Published: 2023-12-25  

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