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Psy-hiPSC microglia

Financiado

Functional impact of the psychiatric risk gene CACNA1C in human iPSC-derived mic...

Psychiatric disorders such as major depression, bipolar disorder, schizophrenia, and autism are highly prevalent chronic diseases. However, their underlying pathophysiology is still largely unknown. Genomic studies have identified... ver más

31/08/2026

UNIVERSITY OF EAST...

200K€

Presupuesto del proyecto: 200K€

Líder del proyecto

ITASUOMEN YLIOPISTO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-26

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

HORIZON-MSCA-2022-PF-01-01: MSCA Postdoctoral Fellowships 2022

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1 Participantes

UNIVERSITY OF EASTERN FINLAN...

199.69K€ | Lider

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Últimas noticias

30-11-2024: Cataluña Gestión For... Se ha cerrado la línea de ayuda pública: Gestión Forestal Sostenible para Inversiones Forestales Productivas para el organismo:

29-11-2024: IDAE En las últimas 48 horas el Organismo IDAE ha otorgado 4 concesiones

29-11-2024: ECE En las últimas 48 horas el Organismo ECE ha otorgado 2 concesiones

Duración del proyecto: 40 meses Fecha Inicio: 2023-04-26
Fecha Fin: 2026-08-31

Líder del proyecto

ITASUOMEN YLIOPISTO

TRL 4-5

Presupuesto del proyecto 200K€

Descripción del proyecto Psychiatric disorders such as major depression, bipolar disorder, schizophrenia, and autism are highly prevalent chronic diseases. However, their underlying pathophysiology is still largely unknown. Genomic studies have identified single nucleotide polymorphisms (SNPs) in the CACNA1C gene that are robustly associated with all of these major psychoses. Among these is the main non-coding risk SNP rs1006737. Beyond that, a gain-of-function mutation in CACNA1C has been described, which causes a multiorgan phenotype including severe cardiac arrhythmias, immune deficiency, cognitive abnormalities, and autism, named Timothy syndrome (TS). Immune alterations plus the involvement of their primary mediators in the brain, the microglia, have also been reported for psychiatric disorders. Based on this, we aim to introduce the risk A-allele of the CACNA1C SNP rs1006737 as well as the TS mutation G406R into human iPSC control lines using CRISPR base editing. The generated isogenic lines are then differentiated into iPSC-derived microglia cells (iMGs) and undergo a systematic functional characterization, including the analysis of transcriptomic profile, intracellular calcium levels, motility, phagocytic activity, cytokine release, cellular bioenergetics, and mitochondrial parameters. Furthermore, the newly created iMG cultures are tested in brain organoid systems to assess their effects on neuronal activity and function via multielectrode array recordings and single nuclei sequencing. The obtained results will contribute significantly to elucidating whether microglial function is causally affected by the selected CACNA1C risk variants, what underlying checkpoint mechanisms are involved, and whether these changes compromise microglia-neuron interactions, thereby impairing neuronal activity and function. Overall, this study will add to a better understanding of the role microglia play in the pathogenesis and/or progression of CACNA1C-associated psychiatric disorders.

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