Research Group "Structure and Dynamics of Molecular Machines"
The survival of all organisms depends on the faithful transmission of genetic material from one generation to the next. In cells, this process is conducted by large, multi-subunit assemblies, termed replisomes, that couple the unpackaging of DNA within the parental chromosomes with the synthesis of new DNA strands. Karl Duderstadt and his Research Group “Structure and Dynamics of Molecular Machines” seek to define the operating principles that guide replisome function and ensure efficient chromosome duplication.
The figure shows a structural model of the bateriophage T7 replisome in operation. Parental duplex DNA (gray) is unwound by a helicase (blue) which generates two single-stranded templates for the synthesis of new daughter strands (orange) by several DNA polymerases (green/yellow). In the model shown, one strand is copied continuously while a single-stranded loop bound by proteins (red) forms on the other prior to synthesis.
A particular focus of the group is to understand how daughter-strand synthesis is coordinated and the molecular events that trigger loss of coordination. Thereby they want to understand the molecular origins of duplication errors that underlie many serious human diseases. The scientists employ a combination of structural, biochemical, and cutting-edge single-molecule methods to study these processes with the highest spacial and temporal resolution.
The long-term vision is to use these studies to develop a general framework for understanding how interaction networks can evolve to guide dynamics events within multiprotein complexes.