Structural biology, and in particular scattering based techniques making use of X-rays and electrons, has provided high-resolution insight in the structure and function of molecules, molecular assemblies, and cells. Despite a lot of advances in instrumentation, radiation damage limits high resolution imaging of biological material using conventional X-ray or electron based approaches. X-ray free-electron lasers (FELs) exceed the peak brilliance of conventional synchrotrons by almost 10 billion times. They promise to break the nexus between radiation damage, sample size, and resolution by providing extremely intense femtosecond X-ray pulses that pass the sample before the onset of significant radiation damage.
Since light is an important environmental variable, many organisms have evolved signalling pathways that transmit and thereby translate this stimulus into various biochemical activities. Recently, new classes of blue light photoreceptors have been identified that use flavin based photosensors. The photosensor domains are coupled to an array of other domains, including kinases and transcription factors. We are mainly studying proteins containing LOV and BLUF domains as photosensors using structural (diffraction, scattering), biochemical and in collaboration quantum chemical approaches. Together with spectroscopic data, their combination allows to understand on a molecular level how absorption of a blue light photon results in a specific structural change of the protein that triggers a secondary signal resulting in a biological event (see e.g. Nature 459: 1015-1018 (2009)). We aim to exploit this knowledge to design new photoreceptors for application in cell biology (see e.g. Nature 461: 104-108 (2009)).
RNA is the exclusive messenger that forwards genetic information for protein synthesis to the ribosome. In eucaryotic organisms, genes are transcribed into messenger RNA (mRNA) by RNA polymerase II in the nucleus. The pre mRNA resides in the nucleus and becomes processed until the mature mRNA can shuttle into the cytosol via the Nuclear Pore Complex. RNA processing conveys protecting attributes to the RNA that makes the RNA more stable but it also ensures protein diversity. For instance, the cap structure protects RNA from 5' - 3' degradation, and different splicoforms of one gene are transcribed, respectively. Thus, mRNA processing is a basic important event in the nucleus that heavily influences gene expression and gene diversity.
The performance of instrumentation for the precise biochemical characterization of proteins has increased dramitically in recent years, primarily as a result of improvements in computer hardware. This is particularly obvious in the field of mass spectrometry, where newer instruments show increases in resolution and sensitivty of more than 1000-fold over instruments dating from the year 2000, and in robotics, where sophisticated as well as dedicated instruments have become affordable and usable, even for small groups of users.
The discovery of anammox bacteria in the 1990's has dramatically changed our understanding of the global nitrogen cycle. These bacteria perform ANaerobic AMMonium Oxidation (ANAMMOX), combining ammonium with nitrite into molecular dinitrogen (N2) and water, yielding energy for the cell. This process relies on highly unusual intermediates such as hydrazine. We are studying the molecular mechanism of the ANAMMOX process using structural biology.[mehr]