RESEARCH
Within each of our cells we have 2 meters of DNA material that need to fit inside a 10 μm nucleus. To achieve this, our genome folds upon itself forming an incredibly complex and intertwined structure.
Spread throughout the genome humans have around 25.000 genes that need to be turned on and off in specific cells at precise times by coming in physical proximity with small regulatory sequences named enhancers.
Our lab aim is to understand how the 3D genome facilitates the correct enhancer-gene interactions in space and time to ensure precise and robust gene expression patterns in health and development.
To disentangle the 3D regulatory genome we focus on the following main questions:
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- How is regulatory specificity between enhancers and genes achieved within the Topologically Associating Domains (TADs) that compartmentalize the genome?
- How does the molecular machinery that mediate the establishment of enhancers -promoter communication interact with the proteins responsible for the folding of the genome?
- How does the spatial arrangement of the different genome regulatory elements influence gene activity and transcription dynamics.
Tools and models
The laboratory uses the fly Drosophila melanogaster as its main model organism. Our research is focused on the first 3h of embryogenesis, when the main gene regulatory networks that pattern the fly body plan are specified. We use a combination of CRISPR-cas9 genome editing and single-cell transcription live-imaging tools to visualize and quantify transcriptional dynamics of endogenous genes in living embryos. To measure the genome’s 3D structure, we use high-resolution chromosome conformation capture assays (Micro-C). In addition, a set of varied molecular biology and functional genomic tools are used to determine how the 3D genome impacts gene regulation.
Quantitative single-cell transcription live-imaging
High-resolution genome-wide chromosome conformation capture
