brainTEaser
Financiado
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...
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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Duración del proyecto: 29 meses
Fecha Inicio: 2023-04-19
Fecha Fin: 2025-09-30
Fecha Fin: 2025-09-30
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-19
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2022-PF-01-01:
MSCA Postdoctoral Fellowships 2022
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
207K€
Líder del proyecto
LUNDS UNIVERSITET
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5