In our lab, we use the developing mouse limb as a model to gain fundamental knowledge into the cellular and molecular mechanisms that control organogenesis. To do so, we combine the strengths of genetic analysis in the mouse with the use of functional genomics to get mechanistic insight into these developmental processes.
Currently, our main areas of interest are:
1) Transcriptional integration of SHH signaling. The SHH ligand is essential for the formation of the distal limb. We are trying to understand how limb mesenchymal cells integrate the concentration and timing of SHH exposure and elaborate accordingly a transcriptional response. To do so, we are functionally dissecting the regulatory landscapes of SHH-responding genes in the mouse limb using CRISPR-Cas9 technologies and transgenic reporter assays.
2) Evolutionary diversification of the limb. Tetrapods have conquered all habitats on Earth thanks to the specialization of their limb anatomy for running, flying, burrowing, swimming, etc. These adaptations involve all sorts of anatomical alterations of the limb, including the gain/loss of digits, changes in the size and shape of bones, etc.
In the lab we combine quantitative gene expression analysis and functional epigenomics (ATAC-seq, ChIP-seq, 4C-seq) in mouse, chicken and pig embryos to identify divergent regulatory strategies in the genomic landscapes of genes with essential functions in limb development. The functional relevance of the candidate alterations is later addressed by modification (deletion, replacement, etc.) of the selected regulatory region in the mouse genome using CRISPR/Cas9 methods.
3) In addition, we are interested in deciphering the mechanisms that specify the different populations of skeletal stromal cells. To do so, we take advantage of genetic lineage tracing and single cell functional genomics. In particular, we are interested in the therapeutical use of these cells, given their strong immunoregulatory properties.
These are exciting times to study how form is encoded in the genome and which are the mechanisms behind morphological evolution! If you are interested in joining the lab for your PhD/Master thesis or as a postdoctoral fellow, please send your CV and motivation letter to firstname.lastname@example.org