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The role of transposable elements in human brain evolution

The human brain is the largest and most complex of all primates possessing unique cognitive functions but also suffering from neurological disorders. However, little is known about primate brain development and the modifications e... ver más

30/09/2025

LUNDS UNIVERSITET

207K€

Presupuesto del proyecto: 207K€

Líder del proyecto

LUNDS UNIVERSITET 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 2023-04-19

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

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1 Participantes

LUNDS UNIVERSITET

206.89K€ | Lider

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Duración del proyecto: 29 meses Fecha Inicio: 2023-04-19
Fecha Fin: 2025-09-30

Líder del proyecto

LUNDS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 207K€

Descripción del proyecto The human brain is the largest and most complex of all primates possessing unique cognitive functions but also suffering from neurological disorders. However, little is known about primate brain development and the modifications enabling brain enlargement as primate tissues are not available at early developmental time points. Only few changes occurred in protein-coding genes; thus, significant differences must be present in gene regulatory processes. It is essential to analyse primate models to identify and understand molecular features unique to the human brain. Transposable elements (TEs) are mobile pieces of DNA comprising 50% of primate genomes. They can contribute to genome evolution as they carry regulatory sequences and have been found to serve for example, as enhancers and alternative promoters. Moreover, TEs are insertional mutagens leading to genetic disease. They are silenced by repressive marks including DNA methylation. Interestingly, methylation can sometimes spread and impact adjacent regions making TEs noteworthy candidates for methylome evolution. Due to their challenging analysis and lack of primate material, the role of TEs in primate brain development and human brain evolution has not been investigated thoroughly. Here, I propose that human-specific TE insertions have the capacity to act as repressors and silence genes in brain development. Exploiting human and non-human primate cerebral organoids as a model for brain development, and Oxford Nanopore Technologies long-read DNA sequencing to detect DNA methylation, I will analyse locus-specific TE methylation spread to nearby genes. Using differential expression analysis and CRISPR-Cas9 genome editing, I will assess the effect of putative repressor TEs on gene expression revealing if the repression of specific loci contributed to human brain enlargement and gain of cognitive functions.

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