The clarification of biomolecular architecture responsible for disease images and their treatment via optical and non-optical superresolution microscopy and spectroscopy techniques.

A combination of nanoresolution microscopy techniques, such as atomic force microscopy (AFM) Fluorescence Imaging with One Nanometer Accuracy (FIONA) and tip enhanced Raman spectroscopy (TERS), will be used to study the biomolecular interactions of ligands with DNA and the impact of this interaction on the DNA structure. At first the binding of lens epithelium derived growth factor (LEDGF/p75) with chromatine will be studied. The information that will be obtained with this study is crucial to understand the tethering of IN to DNA/chromatine by LEDGF/p75, which will be studied in the second part. Finally, the effect of compounds which are known to inhibit the IN LEGF/p75 binding on the tethering process will beinvestigated. Rutheniumcomplexes are promising new antineoplasic drugs.They can be photoactivated and thereby affect the DNA structure. Some of them are also shown to induce a kink in DNA molecules. This kinking, together with their possible sequence selectivity for binding, will also be investigated. Finnaly, the effect of histone proteins in chromatine on binding will be studied.