Transcriptional Regulation Assessed in Neuronal Subtypes in three major interrelated Psychiatric disorders

Informations projet

TRANS-PSYCH

N° de convention de subvention: 101078437

DOI

10.3030/101078437

Date de signature de la CE 8 Mai 2023

Date de début 1 Août 2023

Date de fin 30 Septembre 2028

Financé au titre de

• European Research Council (ERC)

Coût total

€ 1 499 999,00

Contribution de l’UE

€ 1 499 999,00

Coordonné par

ACADEMISCH ZIEKENHUIS GRONINGEN
Netherlands

Periodic Reporting for period 1 - TRANS-PSYCH (Transcriptional Regulation Assessed in Neuronal Subtypes in three major interrelated Psychiatric disorders)

Période du rapport: 2023-08-01 au 2026-01-31

Résumé du contexte et des objectifs généraux du projet

Schizophrenia, bipolar disorder, and major depressive disorder are interconnected psychiatric conditions with shared neurobiology. However, their underlying mechanisms remain poorly understood. Existing testing models face significant limitations, highlighting the need for new approaches. The ERC-funded TRANS-PSYCH project aims to develop organoid models for these psychiatric disorders by targeting upstream transcription factors critical for cell type differentiation and neuronal network formation. The central hypothesis is that these transcription factors can serve as targets for modelling these disorders in brain organoids. The project will leverage multi-omics profiling on a high-quality collection of psychiatric human brain tissue to identify key transcription factors, which will then be targeted in brain organoid systems to create neurobiological models of psychiatric disorders.

The neuronal transcriptional regulators that mediate these psychiatric disorders are currently unknown, and difficult to identify and validate. Novel genomics technologies allow for an unbiased characterization of the brain in order to detect cell types and genes that are dysregulated in disease, and can be used to identify putative upstream transcription factors. Therefore, our research objectives are outlined as follows:
1) deep molecular characterization of brain tissue,
2) identification of genetic risk mechanisms, and
3) generation of brain organoid models.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

1) We have processed high-quality tissue of brain donors diagnosed with psychiatric disorders of interest and are performing multi-omic analyses.
2) We have generated a library of prioritized genetic risk factors for downstream investigation using in vitro models.
3) We are establishing a brain organoid platform to investigate genetic risk factors relevant to psychiatric disorders.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Our efforts to integrate phenotypic (clinical) and genetic data, in order to interpret our transcriptomic signatures have been received positively by bioinformaticians at the BioSB 2025 conference. This integration strategy is advancing the research field of psychiatric disease studies beyond the state-of-the-art. We envision that upon transcriptome profiling, this comprehensive analysis will significantly advance the field when shared with the broader scientific community (e.g. preprint release and manuscript publication

Holtman Lab

ERC Project Overview