I am interested in the molecular function and regulatory mechanisms of transcription in eukaryotic species. Current projects in my research group revolve around RNA polymerase I (Pol I) that produces ribosomal RNA – building blocks of cell’s protein factories, ribosomes. The synthesis of ribosomal RNA by Pol I accounts for >60% of total transcription in growing eukaryotic cells and constitutes the rate-limiting step of ribosome biogenesis. Oversupply of ribosomes tightly links with accelerated cellular proliferation, while shortage induces cell cycle arrest, senescence or apoptosis in different cell types. To balance the capacity and demand of protein synthesis, many signaling networks that control cell cycle regulate Pol I. Importantly, dysregulation of Pol I activity is linked to the etiology of many human cancers and hereditary disorders.

To understand on the molecular level how the function of RNA polymerase I is regulated in normal and sick cells, we aim to elucidate the identity and sequence of molecular events that take place at the beginning of Pol I mediated production of ribosomal RNA. Our research approach depends on sophisticated biochemical, enzyme kinetic and single-molecule biophysics tools that we develop to monitor the function of Pol I in real-time. The molecular mechanisms that we will uncover pave the way for the development of new drugs that specifically constrain the function of Pol I and hence potentially slow down the progress of cancer and other diseases.