Molecular Biophysics

- DNA passing through a nanopore

- Top-view of a G-quadruplex
In Vitro studies
The group will provide a unique capability of single-molecule studies in vitro, which will directly probe the basic processes on the single-chain protein/DNA/RNA level. The techniques involve optical micromanipulation and Atomic Force Microscopy, and the use of nanopores to detect and analyse individual molecules either by voltage-driven transport or diffusion.
Questions to be addressed include the characteristics of biological macromolecules on the single molecule level in aqueous solutions, and their interaction with specific environments. Nanopores, both biological and solid-state based, allow acquisition of thousands of single molecule events in a few hours and thus are interesting for drug screening or sequencing. Techniques for supported lipid bilayers will be developed, providing new approaches for sensory applications and in vitro studies of biological nanopores like the nuclear nanopore complex.
Nucleic Acids
The double helix is not all there is; other structural forms are important for regulating gene activity. In particular, guanine-rich sequences can form four-stranded structures. These structures can be studied biophysically, using ultraviolet and Circular Dichroism spectroscopy as well as fluorescence techniques like Fluorescence Resonance Energy Transfer. Bioinformatics can then be used to predict where the sequences form in the human genome, and hence predict their function. These G-Quadruplexes can control gene transcription and translation - especially in cancers. By testing quadruplex-binding ligands, specific drugs can be developed. Evolutionary studies tell us about the history of these structures.

