LBR research topics and support activities
Biomolecular ComplexesProteins and their interaction networks are at the heart of life. Understanding how diverse proteins come together spatially and temporally and how their specific complexes translate into cellular functions is important to understand health and disease but represents a major challenge. Microtubules are filamentous structures fundamentally involved in diverse cellular processes ranging from cell division, motility and polarity to signaling and intracellular transport. They are also key to form centrioles of centrosomes and axonemes of cilia and flagella. Because of their important role for cell survival, the malfunctioning of the microtubule cytoskeleton is associated with several severe human pathologies including cancer and various forms of ciliopathies as well as cardiovascular, infectious and brain diseases. We use X-ray crystallography in combination with biochemical and biophysical methods to investigate how proteins and drugs regulate the structure, function and dynamics of the microtubule cytoskeleton.
Michel Steinmetz, Laboratory head and group leader
Regulation of microtubule structure, function and dynamics
Andrea Prota, Scientist
Molecular mechanisms of microtubule-targeting agents
Natacha Olieric, Scientist
Microtubule cytoskeleton of parasites
In memory of Guido Capitani (1970 – 2017)
Structural Biology of Membrane ProteinsClass A G protein-coupled receptor (GPCRs) transduce extracellular signals across the cell membrane by activating cytoplasmic-bound heterotrimeric GTP binding proteins (G proteins), which, in turn, modulate the activity of downstream effector proteins. Despite the physiological and pharmacological relevance of GPCRs, the structural basis of ligand efficacy and receptor activation, and how these elements translate into cytoplasmic trafficking and cellular response still remain elusive. In the Laboratory for Biomolecular Research we integrate data from structural biology, molecular biology, cellular biology and structural bioinformatics to study the molecular basis of GPCR function. Specifically, we aim to obtain the crystal structure of the complexes between GPCRs and their cytoplasmic partners, the centerpieces that connect extracellular stimuli to intracellular signals. In addition, we plan to compare the profile of activated signaling molecules with their dynamic intracellular localization pattern to learn how receptor activation translates into specific pathways of cellular signaling. Combination of the data resulting from the study of different Class A GPCRs will allow us to obtain a global picture of GPCR signaling. Our goal is to link receptor structure, cellular biological data and pharmacological results to physiological function.
Gebhard Schertler, Division head and group leader
G protein-coupled receptors (GPCRs)
Valerie Paneels, Scientist
Rhodopsin dynamics and retina tissue imaging
Ching-Ju Tsai, Scientist
Signalling through membrane proteins
Xavier Deupi, Scientist
Molecular basis of activation in G protein-coupled receptors
Applied Molecular BiologyThe availability of recombinant proteins in a high quality and quantity has a profound impact on basic and applied research. We produce milligram amounts of crystallization-grade samples of soluble and membrane proteins in pro- and eukaryotic cells. Using our expertise in recombinant protein production combined with protein-engineering, biochemical, biophysical and structural characterization by X-ray crystallography and cryo-electron microscopy, we currently focus on two main areas:
- We collaborate with industrial and academic partners on applied research projects that are critically dependent on the availability of high-quality recombinant proteins.
- We work on proteins that are of medical relevance and therefore are of interest for applied research. They include botulinum neurotoxins and their receptors, G protein-coupled receptors (GPCRs), and several bacterial/eukaryotic membrane proteins.
Botulinum Neurotoxins and GPCR crystallization Tools
Xiaodan Li, Scientist
Time-Resolved CrystallographyProtein function is critically dependent on coordinated motions induced by interactions with ligands, other proteins or changes in environment. Insights into the complex structures of proteins and knowledge of protein motions throughout their conformational landscape have tremendous impact on biology. The dynamic interaction between ligands and their protein partners is the molecular basis for pharmacological intervention in human disease.
We are using cutting edge X-ray technologies to track ligand-protein interactions over time and resolve conformational states important for protein function. To achieve this aim we firmly establish time-resolved serial crystallography at the Swiss Light Source (SLS) and the Swiss Free Electron Laser (SwissFEL). Structural snapshots over time are complemented with spectroscopy and computational simulations to provide clear cause-and-effect descriptions of stepwise structural rearrangements in a range of protein targets including membrane pumps and G protein-coupled receptors.
Jörg Standfuss, Group leader
Serial crystallography using synchrotron radiation and free electron lasers
Tobias Weinert, Scientist
Mechanisms of Signal TransductionInteractions between the cell and its environment, as well as between cellular compartments, occur at the biological membranes. A variety of membrane proteins and protein complexes perform tasks associated with the reception of the extracellular signals and conversion of those signals into biochemical responses inside the cell. We are using protein biochemistry, biophysics and structural biology (X-ray crystallography and cryo-EM) to investigate the structure and function of membrane proteins involved in signal transduction and cholesterol recognition.
Volodymyr Korkhov, Group leader
Structure and function of membrane proteins involved in cholesterol recognition and signal transduction
Vocational Training and Chemical ManagementThe Vocational Training and Chemical Management group has its focus on following three topics:
- Vocational training for technicians in chemistry
- Chemical Management (PSI wide)
- Laboratory Support for LBR and LNB