Lipodystrophic laminopathies, genome organization and adipose stem cell function
The nuclear envelope regulates genome function by interacting with chromatin. The nuclear envelope consists of a double nuclear membrane and the nuclear lamina, a meshwork of intermediate filaments called lamins. Mutations in A-type lamins cause diseases called laminopathies; these include partial lipodystrophies, muscle dystrophies and premature aging. Laminopathies mainly affect mesodermal tissues, suggesting metabolic and differentiation defects in mesenchymal stem cells (MSCs).
We use patient cells and engineered adipose stem cells, in combination with biochemical, genomics and imaging approaches to address the impact of lipodystrophic LMNA mutations on genome organization and adipose tissue function (Oldenburg et al 2014 Hum Mol Genet; Oldenburg et al. in revision).
- Dr. Nolwenn Briand
Funded by the Research Council of Norway, the University of Oslo and the Norwegian Center for Stem Cell Research.
Function of histone variant H3.3 in pediatric glioblastomas
Around 80% of a form of pediatric gliomas (DIPGs) correlate with mutations in H3.3, the most prominent being H3.3K27M. H3.3K27M expression results in a global reduction in H3K27me3. Using patient cells and various cellular models and experimental approaches, we are unveiling pathways of H3.3 deposition in chromatin (Delbarre et al. 2013 Genome Res; Ivanauskiene et al 2014 Genome Res; Delbarre et al 2017 Genome Res).
We also work to determine how mutated H3.3 influence global chromatin architecture, gene positioning and function in glioblastoma multiform.
- Dr. Erwan Delbarre
Funded by the Cancer Society.
Computational modeling of the 3D genome
The 3-dimensional (3D) layout of the genome influences cell- and time-specific blueprints of gene expression. We are developing integrated pipelines for analysis and representation of various epigenetic datasets, chromosome conformation capture data (4C, Hi-C) and gene expression patterns in human cells. Our recent platform, Chrom3D, integrates Hi-C and nuclear lamin ChIP-seq datasets to generate 3D models of chromatin taking into account interactions between topologically-associated domains (TADs) and lamin-associated domains (LADs) to provide radial positioning information (Paulsen et al. 2017, Genome Biol).
- Dr. Jonas Paulsen
Funded by the Research Council of Norway and the University of Oslo.