Project description
A 4D model of development
Development is an intriguing process whereby a whole organism emerges from a single cell. Despite comprehensive research, we do not fully understand how such an extensive cellular diversity emerges from the genome. Funded by the Marie Skłodowska-Curie Actions programme, the 4D Development project aims to provide answers to this key question in biology by measuring cell transcription in Drosophila melanogaster during its ten-day development. Researchers will measure the spatial gene expression of 1 600 genes at single-cell resolution every 4 hours and use this data to reconstruct 3D and 4D models. This promises to uncover the gene regulatory networks driving development of Drosphila and lead to an understanding of more complex animals including mice and humans.
Objective
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.
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesbasic medicineanatomy and morphology
- agricultural sciencesagriculture, forestry, and fisheriesagriculturehorticulturefruit growing
- natural sciencesbiological sciencesgeneticsgenomes
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Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
9052 ZWIJNAARDE - GENT
Belgium