Biomolecular Complexes
Proteins 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, Head of PSI Center Life Sciences and Group leader
Regulation of microtubule structure, function and dynamics
Andrea Prota, Scientist
Molecular mechanisms of microtubule-targeting agents
In memory of Guido Capitani (1970 – 2017)
Structural Biology of Membrane Proteins
Class 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. We integrate data from structural biology, molecular biology, cellular biology and structural bioinformatics to study the molecular basis of GPCR function. In addition, we 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. Our overreaching goal is to link receptor structure, cellular biological data and pharmacological results to physiological function.
Gebhard Schertler, Group leader
G protein-coupled receptors (GPCRs)
Valerie Panneels, 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
Protein Engineering
Microbial pathogens cause billions of infections and millions of deaths per year. Detailed knowledge of host-pathogen interactions is therefore fundamental to develop measures to treat infectious diseases caused by microbial pathogens. Using X-ray crystallography and cryo-electron microscopy combined with biochemical and biophysical methods, we study proteins that are relevant for infectious diseases, including botulinum neurotoxin, their receptors and the oxaloactetate decarboxylase complex. Furthermore, we collaborate with industrial and academic partners on microbial pathogen-related research projects that are critically dependent on the availability of high-quality recombinant proteins and their biophysical and structural characterization.
Richard Kammerer, Group leader
Botulinum Neurotoxins and Receptors
Xiaodan Li, Senior Scientist
Structure and function of Membrane proteins related to ion transport
Time-Resolved Structural Biology
Protein 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 establish time-resolved serial crystallography at the Swiss Light Source (SLS) and the Swiss Free Electron Laser (SwissFEL). Structural snapshots 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, Laboratory Head and Group leader
Integrative structural biology of dynamic systems
Tobias Weinert, Scientist
Serial crystallography
Mechanisms of Signal Transduction
Interactions 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.
Volodymyr Korkhov, Group leader
Structure and function of membrane proteins involved in cholesterol recognition and signal transduction
Vocational Training and Chemical Management
The Vocational Training and Chemical Management group has its focus on the following three topics: (i) Vocational training for technicians in chemistry; (ii) PSI wide chemical management; (iii) Laboratory support for the LBR and the LNB.
Thomas Rohrbach, Group leader