Projects in Chemical Biology
- Project 1
- Project 2
About half a century ago G. E. Moore (cofounder of Intel) predicted an exponential growth of the transistor density in integrated circuits. While the empiric 'law' still holds amazingly well it is becoming more and more difficult to build even smaller objects: In the majority of cases photolithographic methods are applied and the wave length of the light which is used represents a natural lower limit for the smallest possible feature. In a complementary 'bottom up' approach it should be possible to build up functional architectures with molecules. Among all possible solutions to realize this DNA is a very interesting candidate: It can be easily synthesized and manipulated, its structure is well known and architectures can be "programmed" using the Watson-Crick interaction. One problem, however, is that DNA is a linear polymer. This resembles the task of building objects with cooked spaghetti. To facilitate the assembly of DNA architectures we are using molecules that can sequence-specifically bind to DNA – like for example Dervan-type polyamides. In the simplest approach two of these polyamides are connected to form a 'DNA-strut' which can act as second, orthogonal structural element (besides the Watson-Crick interaction). In a figurative sense these DNA-struts can be seen as sequence-selective glue for DNA origami.
This project is currently dormant.
Regulation of Biological Activity
One of our research interests is the spatiotemporal control of the activity of biologically active compounds and in the current studies we want to put DNA- and RNA-based applications under the control of light as trigger signal. Nucleic acids and their derivatives and analogues can be used for a variety of applications ranging from gene regulation (RNA interference, antisense strategy etc.) over the modulation of protein function (for example with aptamers) to molecular diagnostics and beyond. On the other hand light is an ideal trigger signal which can be used for addressing single cells in thin tissues or small organisms. With (confocal) microscopes it is possible to both visualize the sample of interest and irradiate certain areas with spatiotemporal and dosage control. Thus, one of our goals is for example to address questions in developmental biology via the spatiotemporal gene regulation with light.
By modification of the nucleobases the nucleic acid of which it is part becomes temporarily inactive. The derivatives shown below have for example been synthesized and incorporated in DNA. It could be shown that it is possible to control transcription with light, as well as regulate the activity of an aptamer, induce conformational changes in nucleic acids and construct an anticoagulant with light-triggered antidote activity.
Thus our research is located right at the interface between chemistry and biology/medicine as well as physics with organic synthesis as our central element. The methods we use range from the entire repertoire of organic synthesis on "flask-scale" over automated and manual solid phase synthesis, MPLC, HPLC, the full scale of characterization methods (2D-NMR, HPLC-MS, etc.) to biochemical and molecular biological procedures (electrophoresis, PCR, cloning, surface Plasmon resonance, FCS, etc.), cell culture (pro- and eukaryotic) and microscopy including nonlinear optics as well as atomic force microscopy.