Research interests

Our research aims at understanding how proteins achieve their unique functional properties. We study ligand binding and catalysis in model systems, in particular heme and flavin containing proteins. Both cofactors allow for a plethora of different reactions, yet, most of the enzymes are highly specific catalysts. Thus, an important question is how does the protein fine-tune the reactivity of the cofactor and of the intermediates occurring during the reaction? Crystal structures combined with kinetic data provide a blueprint and suggest possible reaction mechanisms that may be tested using molecular biology and biochemistry. Key insight is obtained from crystal structures of reaction intermediates. Their determination is rather difficult due to the fleeting existence of the species investigated and require development of appropriate experimental schemes.

Light is an important environmental variable and many organisms have evolved sensors to respond to it, e.g. by blue-light-sensitive flavoproteins. Ultimately, we want to understand the flow of events that starts with the absorption of a blue light photon by the isoalloxazine ring to generate an excited singlet or triplet state followed by a photochemical reaction that can further trigger large scale structural changes of the protein which are linked to (in)activation of other domains involed in signaling cascades. We are mainly studying proteins containing LOV or BLUF sensing domains. The potential for remodelling the systems for practical applications (e.g. neurophotonics) is actively persued.

A recent interest is the application of X-ray Free Electron Lasers (FELs) or flash-imaging biological samples. An important aspect of any method development is the availability of suitable test samples. We are identifying, designing, and generating samples with the appropriate symmetry, size and modularity, adapted to the decreasing wavelengths of the FEL radiation available, to probe the limits of diffractive coherent imaging approaches, including the influence of radiation damage on the resolution and "meaning" of the structure (identity of electronic states being imaged). This highly exploratory branch of our research is part of a big international collaboration.

 

Methods applied

Static and dynamic X-ray diffraction and scattering, Biophysics, Biochemistry, Molecular Biology, Diffractive Imaging