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Deep representational learning of the evolutionary DNA code in the vertebrate pallium

Project description

A closer look at cell identity in vertebrate genomes

The complexity of vertebrate genomes presents a challenge: despite having tens of thousands of genes, only a few stable cell types are produced. Understanding how these cell types are encoded remains a puzzle. Gene regulatory elements, which control gene expression, play a crucial role but are less conserved than genes and can be far from their target genes. Supported by the Marie Skłodowska-Curie Actions programme, the EvoDCode project explores how genomic sequences dictate cell identity in the pallium across vertebrates. Using cutting-edge single-cell sequencing and machine learning models, the project aims to map regulatory elements and their role in species-specific and conserved cell types, providing new insights for evolutionary biology and therapeutic applications.

Objective

Vertebrate genomes consist of tens of thousands of genes and yet they produce only a limited number of stable cell types. Our understanding of how cell types are encoded in the genome is still lacking. The expression of genes is controlled by gene regulatory elements, which are evolutionarily much less conserved than genes are and can be located far away in the genome. My main goal is to better understand how the genomic sequence underlies cell identity in the pallium across vertebrate species and I hypothesize that gene regulatory logic can be directly learned from the genomic sequence and used to predict cell types. Recent advances in the field of single cell sequencing have made the generation of large epigenomic datasets possible, while novel machine learning models like DNA language models are providing unprecedented insights into the regulatory logic of the genome. In addition, for many non-model species high quality reference genomes are becoming available as there is an increased awareness for the need to preserve biodiversity.
I will conduct single cell multiome sequencing, supplemented with low-cost single-cell ATAC-seq using the HyDrop platform - developed in the host-lab - to profile regulatory elements across cell types in the pallium from multiple species, including mammals, birds, lizards and fish. My experience in generating and annotating single cell data from the brain will aid in the analysis and alignment of the generated datasets. Next, I will use this data to study the relationships between the genome of a species and the identified cell types by training species-aware DNA language models and using these models to identify species-specific and conserved regulatory logic. These models will not only be interesting from an evolutionary perspective, but also aid in ongoing efforts to develop synthetic enhancers used to target highly specific cell types, which can be applied in many therapeutic applications.

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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-2024-PF-01

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Coordinator

VIB VZW
Net EU contribution

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€ 200 400,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
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