Project I.) Nuclear Organization
Nuclear architecture is not only important for the efficient compaction and decompaction of the genome during cell division, but has important functions in coordinating gene regulatory networks and orchestrating cellular identity. Changes in nuclear organization are considered an important complement to epigenetic mechanisms contributing to robust and stable gene silencing. Recruitment of Polycomb Group (PcG) proteins to their target genes not only modulates local chromatin structure but also mediates distant interactions between regulatory sequences and shapes the global nuclear architecture, thereby regulation gene silencing at multiple scales. However, how the multiple layers of Polycomb regulation interconnect mechanistically to reinforce each other’s activity remains unclear. In our group we address the cause-consequence relationship Polycomb-mediated gene regulation and subnuclear chromatin organization?
Project II.) Transcription traffic control:
Gene transcription is fundamental to all life. The recent developments in genomics and bioinformatics have unveiled an unexpected complexity of the eukaryotic transcriptome. A surprise that emerged is the prevalence of transcription on antisense orientation of protein-coding genes. While the genome-wide role for antisense transcription is subject of obvious interest, its sheer existence can come at a cost for genome integrity. RNA Polymerases (RNAPII) transcribing opposite strands cannot bypass each other and head-to-head RNAPII collisions are likely to be harmful for the cells leading to gene blockage, backtracking or DNA damage. . In our group, we combine cell biology, molecular biology, biochemistry, mathematical modelling and single-molecule approaches to understand how transcription of sense/antisense gene pairs is coordinated at the single locus level to avoid transcriptional conflicts, such as RNA polymerase II head-to-head collisions.