Project description
Transposable elements and human brain evolution
The human brain is unusually large and complex, enabling advanced cognitive abilities. However, because early primate brain tissues are inaccessible, we lack complete understanding of how the human brain evolved. With the support of the Marie Skłodowska-Curie Actions programme, the brainTEaser project is working under the hypothesis that changes in gene regulation play a key role in brain evolution. The work will focus on transposable elements (TEs), mobile DNA sequences that make up half of primate genomes and can influence gene activity. Using human and non-human primate brain organoids, the study will examine whether human-specific TEs silence nearby genes through DNA methylation. Collectively, brainTEaser will provide fundamental insight into human brain enlargement and cognitive 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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology cognitive neuroscience
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics genomes
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2022-PF-01
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22100 Lund
Sweden
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