Gene regulation and morphogenesis

We have identified multiple nuclear pore proteins (nucleoporins) as regulators of nuclear envelope formation, and we have linked several nucleoporins to the mitotic spindle apparatus that is responsible for segregation of the chromosomes to the daughter cells during cell division. Searching for proteins involved in nuclear envelope breakdown, we also identified the protein kinase VRK1 as an essential regulator of nuclear envelope dynamics and demonstrated that it controls interactions between chromosomes and the nuclear envelope.

Proper gene expression correlates often with positioning of chromosomes within the nucleus. Interactions between chromosomes and proteins at the nuclear envelope is important for correct chromatin organization and gene transcription in a tissue-specific manner. For instance, we identified two histone H3 lysine 9 (H3K9) methyl transferases as being responsible for recruitment of heterochromatin to the nuclear periphery in embryonic cells, whereas a H3K36-binding protein is required in differentiated cells. Moreover, we found that the nuclear envelope proteins emerin is specifically involved in both chromatin organization and regulation of neuromuscular junction activity, which may contribute to Emery-Dreifuss muscular dystrophy in humans.

Finally, we are interested in understanding the links between nuclear organization and aging. We have described how nuclear morphology becomes highly irregular in old individuals of the model organism Caenorhabditis elegans, which is reminiscent of the changes observed in humans suffering from progeria syndromes. We discovered that a mutation in Barrier to Autointegration Factor (BAF) affects gene expression and how this may induce premature aging. Importantly, we identified several genes as potential drug targets for future studies.