Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023)

My research program will investigate how the three-dimensional architecture of the DNA - how the genome is "packaged" - determines the identity of a cell. This research question will deepen our understanding of how cells that make up different tissues and organs in our bodies have different functions (they can be skin cells, or muscle cells, or neurons, etc) although they all share the same genome. Our work will build on our recent findings that a class of proteins called histone variants have a role in packaging the DNA in different ways in cells that have different functions. With NSERC funding, my research group will identify the histone variants that are responsible for differences in DNA packaging between stem cells and their progeny (neurons, astrocytes and oligodendrocytes) in the human brain. Our studies will decipher the code that links a specific DNA architecture with cellular function. The implications of this research for the natural sciences are far reaching. First, we will develop the new concept of DNA packaging programming specific cell functions. We will therefore generate new knowledge and tools that will be readily adapted to scientists working with other developmental systems or with disease models, thereby our work has the potential to seed discoveries in other fields as well. Second, there has been significant emphasis in recent years on regenerative medicine initiatives to convert a given cell into another cell type, for instance differentiating skin cells from a patient affected by a neurological disease into healthy neurons that can be retransplanted into the same patient. Such efforts have been hampered by differentiation barriers erected by the DNA structure of a given cell, which prevents conversion into other cell types. By significantly improving our understanding of the relationship between genome architecture and cell function, our work will open new opportunities to aid regenerative medicine efforts to obtain properly differentiated cells that can be used for clinical purposes. Third, altering chromatin architecture is becoming increasingly easy because of the growing arsenal of compounds that target chromatin remodelling enzymes, some of which have already been approved for use in human subjects. The knowledge generated by our studies will inform targeted approaches that combine specific chromatin remodelling compounds to engineer the desired changes in 3D genome architecture and obtain specific cell types. Fourth, our studies will generate DNA architecture "fingerprints" that will distinguish between cell types. Given our emerging understanding of the tight correlation between DNA architecture and cell function, our research program will offer an unprecedented view of the functional properties of human cells.