The laboratory investigates various aspects of mitochondrial molecular genetics. A major focus of our work is mitochondrial transcription and how this process is regulated in response to the overall respiratory needs of the eukaryotic cell. Much of the work is performed using in vitro biochemistry and a reconstituted system for mammalian mtDNA transcription. We also work to develop small molecular compounds that can be used to direct mitochondrial gene expression.
Recently, we have begun analysing the molecular basis for mtDNA separation. In living cells, mitochondrial morphology is far from static. Instead, mitochondria form a dynamic network, the shape of which is constantly changed by the combined actions of fission, fusion, and motility. mtDNA molecules are evenly distributed within the mitochondrial network and mitochondrial division is linked to mtDNA synthesis. We have recently demonstrated that Topoisomerase 3 alpha is required to resolve a hemicatenane structure that links newly replicated mtDNA molecules together. In future work, we aim to elucidate how these hemicatenane structures are formed and how Topoisomerase 3 alpha activity is regulated in mammalian mitochondria.
We collaborate extensively with the Maria Falkenberg group at the University of Gothenburg. In this work, we analyse the link between mitochondrial transcription and DNA replication. We also have a long-standing collaboration with the Nils-Göran Larsson laboratory at the Max Planck Institute for the Biology of Ageing in Köln and the Karolinska Institutet, Stockholm, which has world-leading expertise in mouse genetics and cell biology. In drug development, we have nice collaborations with the Lead Discovery Center (LDC) in Dortmund, Germany.