Dynamics of Single DNA Molecules
With the advent of single-molecule techniques, new routes to study the structure, dynamics, and function of biological macromolecules have opened. We are interested in experimentally investigating the dynamics of single DNA molecules with these techniques. Our emphasis is on understanding how the topology of a DNA molecule, manifested in e.g. a linear, circular, knotted or super coiled conformation, affects the dynamics of the molecule, its interaction with other molecules like regulatory proteins, and ultimately its biological functions.
For this aim, we are using laser-trapping techniques that allow us to directly manipulate a single DNA molecule and study its dynamics. In particular, a novel optical-tweezer based force measurement technique - femtonewton force spectroscopy - enables us to measure ultra-small force fluctuations with millisecond time resolution and thus gives us unprecedented insight into the dynamics of the molecule.
We are combining these optical methods with modern micro fabrication techniques, such as micro fluidic chips made of silicon elastomers. This will greatly enhance our capabilities to study a wide range of DNA-protein interactions and shed more light on fundamental biological processes such as the transcriptional regulation of gene expression.
We are also using this microfluidic platform to develop in collaboration with the Walter group a single-molecule biosensor for the ultra-sensitive detection of small organic molecules. We hope that such a biosensor will have a multitude of applications ranging from medical diagnostics to the search for life on Mars.