Synthetic Biology and Biomolecular Systems
This research area focuses on understanding the basic mechanisms of biomolecular systems for applications in biomolecular physics, biological chemistry, and molecular medicine. To achieve these goals 3D transmission electron microscopy, single molecule methods such as optical trapping and fluorescence microscopy, bio-analytics and proteomics, and nano-bio-technologies are used.
The following selected research topics list some examples of current activities that are pursued by the MSB principal investigators.
Molecular Devices and Machines
Inspired by the rich functionalities of natural macromolecular assemblies such as enzymes, molecular motors, and viruses, we investigate how to build increasingly complex molecular structures. Our goal is to build molecular devices and machines that can execute user-defined tasks. Molecular self-assembly with DNA is an attractive route toward achieving this goal. DNA origami in particular enables building nanodevices that can already be employed for making new discoveries in biomolecular physics and protein science.
Website of the lab
Proteomics and Bioanalytics
This research focuses on proteomics, chemical biology and biomarker discovery and a range of questions relating to how proteins interact with each other and with active pharmaceutical ingredients, which molecular mechanisms play a role in cancer and how these can be used for individual approaches to clinical treatment. It uses chemical and biochemical methods as well as spectroscopic and bioinformatic high throughput technologies.
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Mammalian cell engineering
It is of growing interest to decipher the patterns of cell-circuit signaling for understanding the (patho)physiology of living organisms. There is also a progression in biomedicine from applying small molecules and proteins to deploying genetically engineered cells as therapeutic agents in patients. Monitoring and controlling genetically defined cells in living organisms is thus of substantial importance. Our research program, therefore, focuses on bioengineering of next-generation molecular sensors and actuators for functional imaging and remote spatiotemporal control of cellular processes with whole‑organ(ism) coverage. We are, in particular, concentrated on gaining genetic control over key logistic processes in mammalian cells such as compartmentalization. In this way, we can install new metabolic pathways and generate self-assembling biomaterials with new, e.g., biomagnetic properties. These genetically controlled biophysical interfaces allow us to establish two-way communication with specific cells that we will bring to bear on future imaging-controlled tissue engineering and cell therapies.
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Integrative Structural Biology
Our research elucidates molecular mechanisms of the functions of biological macromolecules using integrative structural biology. Combining solution NMR, small angle X-ray and neutron scatterning (SAXS, SANS), crystallography and fluorescence methods (FRET, in collaboration) we study dynamic conformations of proteins and RNAs that are essential for their functional activity, in cellular signaling and disease pathways. For these studies we employ protein and RNA engineering tools, for example, to incorporate isotopes and spin labels by segmental ligation. NMR fragment-screening and structure-based approaches are used to develop small molecule inhibitors of drug targets. Researchers at BNMRZ develop new methods and probes for medical MRI imaging (Steffen Glaser), novel NMR methods to study amyloid fibrils linked to neurodegeneration and Diabetes (Bernd Reif), nanodiscs to study dynamics of membrane proteins and associated complexes (Franz Hagn), and structural mechanisms of Hepatitis B Virus (Anne Schütz).
Creation of Synthetic Biological Systems
The remarkable properties of biological systems are the result of complex interactions between multiple components, and thus emerge at the systems level. Biological systems are thus able to respond to their environment, compute, move, reconfigure and evolve. We aim at the construction of synthetic molecular and cellular systems, which generate and display similar behaviors. Our work involves the engineering and study of synthetic gene circuits, the creation of artificial cellular systems and the development of cell-scale robots.
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