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Functions and evolutionary impact of transcriptomic novelties in the vertebrate brain

Objective

Alternative splicing (AS) is the largest contributor to transcriptomic diversification in metazoans. In particular, mirroring their unparalleled morphological and cellular complexity, vertebrate brains show the highest levels of regulated AS known in nature. However, the functions of most of these alternative transcripts, and the evolutionary impact that the increased transcriptional complexity has had on the evolution of the vertebrate brain are still widely unexplored.
In this project, we will investigate the functions and evolutionary impact of neural AS in vertebrates. We will focus on neural-specific alternative exons that are highly conserved across vertebrate groups (suggesting functional importance), but that are not conserved in invertebrates, and are thus vertebrate-specific genomic novelties. We will term these exons Vertebrate- and Neural-specific Alternatively Spliced (VN-AS) exons.
Through a combination of bioinformatics, experimental manipulation in models species, and systems-level network analysis, we aim to: (i) Comprehensively identify VN-AS exons, and study their regulation during vertebrate neurogenesis and nervous system development, using RNA-seq and comparative genomics; (ii) Probe the phenotypic impact of VN-AS exons on vertebrate nervous systems, using the CRISPR-Cas technology for genome editing; and (iii) Investigate how VN-AS exons rewire protein-protein interaction networks in vertebrate neurons – an emergent molecular function for AS –, and whether this rewiring underlies novel functions of VN-AS exons in the vertebrate brains.
This project will thus deliver fundamental insight into two major unanswered questions: (i) what are the functions of transcriptomic diversification, and (ii) how does transcriptomic diversification impact organismal evolution. Our results will fill a large gap of knowledge in our current understanding of brain evolution and development, providing a complementary angle to traditional gene expression studies.

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ERC-STG - Starting Grant

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(opens in new window) ERC-2014-STG

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Host institution

FUNDACIO CENTRE DE REGULACIO GENOMICA
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.

€ 1 498 852,00
Address
CARRER DOCTOR AIGUADER 88
08003 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 498 852,00

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