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4D Development

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Measuring all cells of Drosophila development to reconstruct differentiation tra...

Measuring all cells of Drosophila development to reconstruct differentiation trajectories and understand the language of the genome How the genome regulates the differentiation trajectories that instruct a single fertilised egg to develop into an adult organism is a longstanding question in biology. Here, high-throughput spatial transcriptomics will be leverag... ver más

31/08/2027

VLAAMS INSTITUUT...

192K€

Presupuesto del proyecto: 192K€

Líder del proyecto

VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-04-29

HORIZON-MSCA-2023-PF-01-01: MSCA Postdoctoral Fellowships 2023 Expected Outcome:Project results are expected to contribute to the following outcomes:

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1 Participantes

VLAAMS INSTITUUT BIOTECHNOL...

191.76K€ | Lider

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Duración del proyecto: 40 meses Fecha Inicio: 2024-04-29
Fecha Fin: 2027-08-31

Líder del proyecto

VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 192K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto How the genome regulates the differentiation trajectories that instruct a single fertilised egg to develop into an adult organism is a longstanding question in biology. Here, high-throughput spatial transcriptomics will be leveraged to virtually measure all cellular states of the Drosophila melanogaster. The entire ten-day development of the fruit fly will be sampled with a four-hour interval, where the spatial gene expression of 1,600 genes will be measured in a serially sectioned fly at single cell resolution. The sections will subsequently be reconstructed into 3D models. This approach enables whole-body-biology where a complex measurement is taken of all cells of an entire individual and is here used to densely sample development. In order to reconstruct differentiation trajectories, the 3D fly models will be anatomically aligned between timepoints so that cellular states can be linked and transitions in transcriptional profiles can be studied. The spatial information will substantially simplify this challenge because progenitors and putative progeny will be in the same anatomical compartment. This will generate a 4D developmental model of the fruit fly that links cells, cell types, anatomy and differentiation in space and time. The 4D developmental fly and the cell type trajectories will serve as the manifold onto which single cell transcriptomics (RNA-seq) and chromatin accessibility (ATAC-seq) data will be integrated. Then, Gene Regulatory Network inference tools can be used to identify transcription factors and enhancer sequences that drive lineage decisions. Investigating the enhancer sequences will reveal how cell type specificity is encoded and how the arising complexity is regulated during development. This project will give a unique insight into development, patterning and the emergence of cellular diversity from the genome, and will form an important proof of concept to approach development in other larger organisms such as mice and humans.

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