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The role of transposable elements in human brain evolution

Objective

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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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

LUNDS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 210 187,68
Address
Paradisgatan 5c
22100 Lund
Sweden

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Region
Södra Sverige Sydsverige Skåne län
Activity type
Higher or Secondary Education Establishments
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Total cost

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