The Department explores fundamental and applied research topics in the area of biomaterials, biophysics and biomedicine. Its focus are novel functions and phenomema based on the self-organization of molecules, proteins, nanoparticles, bacteria, and cells as well as their chemical and physical manipulation. In this context we are developing new devices and biomaterial systems (e.g. photoswitchable molecules and proteins, structured interfaces for bio- and optically active interfaces as well as fiber systems for cell matrices) and shedding light on fundamental issues such as individual and collective cell migration, cellular interactions with their environment (cell-cell and cell-matrix adhesion) and, its influence on higher biological functions like immune responses, tissue development and regeneration, wound healing and tumor development.[more]
The visualization and characterization of biologically relevant molecules and activities inside living cells continues to transform cell biology into a truly quantitative science. However, despite the spectacular achievements in some areas of cell biology, the majority of cellular processes still operate invisibly. Further progress will therefore depend increasingly on the development of new (fluorescent) sensors and chemical probes to target and characterize these activities. Our research addresses this need by developing and applying chemical approaches to observe and manipulate protein function in living cells.
ACTIVITIES. Bruce Doak and his group invent and develop novel methods of sample delivery for use at advanced X-ray sources, including X-ray Free-Electron Lasers (XFEL) and fourth generation synchrotrons. Based on their research and development, they design and fabricate well-engineered sample injectors for X-ray scattering facilities worldwide.
Attaining a well defined three dimensional structure and thus functionality can be a serious challenge in the early life of many proteins. Although the final structure is energetically favored, many side reactions can occur mostly leading to aggregation that prevent the formation of the native protein structure. Molecular chaperones are ubiquitous in prokarytic/eukaryotic organisms and form cellular networks which assist protein folding in the cell.[more]
The very detailed behavioral and physiological analyses of our mice with altered GluA1 expression revealed, for the first time, that AMPA receptor plasticity is also critically involved in hippocampus-based learning and memory, thus illuminating the endogenous regulation of AMPA receptors. Several studies from us and our collaborators showed, with no doubt, that AMPA receptors with the GluA1 subunit are not essential for spatial reference memory - the gold standard for spatial learning -, but are critically involved in behavioral tasks for the spatial working memory; a learning deficiency which we could correlate with lack of some forms of long-term potentiation at CA3-to-CA1 hippocampal connections[more]
Following conventional wisdom, the resolution of light microscopy is limited by diffraction to about half the wavelength of light, which is why conventional light microscopes fail to distinguish object details that are closer together than ~200 nanometers. Stefan Hell and co-workers have broken this century-old barrier by developing, since the early 1990's, novel fluorescence microscopes featuring diffraction-unlimited spatial resolution. Thus, they also laid the foundation of a new scientific field: super-resolution fluorescence microscopy, also known as nanoscopy[more]
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 studying proteins containing LOV and BLUF domains as photosensors using crystallographic, biochemical, and 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.
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[more]
Giant viruses and virophages are two groups of DNA viruses that infect single-celled eukaryotes (protists). Encoding hundreds of proteins and featuring particles that are visible by light microscopy, giant viruses are the largest known viruses. Their enormous coding potential renders them host-independent for many biochemical pathways, such as transcription, glycosylation, DNA replication and repair, and allows certain giant viruses to replicate entirely in the cytoplasm. Virophages are smaller DNA viruses that parasitize upon the enzymatic complexity of giant viruses. In co-infected host populations, the virophage inhibits replication of the giant virus and increases host survival. We are interested in the underlying mechanisms of virophage-virus-host interactions and in the diversity and evolutionary history of these viruses.
Structural biology, and in particular scattering-based techniques making use of X-rays and electrons, have 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 and can change in particular redox sensitive cofactors, compromising chemical insight in reaction mechanisms. X-ray free-electron lasers (XFELs) 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.