Stefan Raunser, from the Max Planck Institute of Molecular Physiology in Dortmund, Dirk Görlich from the Max Planck Institute for Biophysical Chemistry in Göttingen, Mathias Gautel from King's College London and Frank Schnorrer from the IBDM in Marseille have teamed up to elucidate the molecular details of muscle formation and function.
This european consortium intends to use its unparalleled expertise and state-of-the-art technologies to address fundamental questions concerning the structure and the function of the sarcomere, the basic contractile unit of skeletal and heart muscle cells. Together, it pursues an innovative, interdisciplinary concept that combines quantitative proteomics and nanoantibody engineering (Görlich) with super-resolution light microscopy (Schnorrer, Gautel), electron cryo-tomography (Raunser), and biochemical as well as functional genetic analyses of sarcomere dynamics in Drosophila flies (Schnorrer), but also in zebrafish and mouse (Gautel).
Prof. Dr. Stefan Raunser, Max Planck Institute of Molecular Physiology, Dortmund
Our research concentrates on the molecular understanding of fundamental cellular processes. Firstly, we are interested in membrane homeostasis in eukaryotic cells and secondly we want to understand the molecular details of muscle contraction. Another focus is on the molecular understanding of the mechanism of action of bacterial toxin complexes.
Our overarching goal is to understand the mechanisms underlying these processes in the healthy and diseased organism in molecular detail. To achieve this, it is essential to elucidate the structure and thus the function of the involved proteins and protein complexes.
We perform structural analyses by single particle cryo-EM and X-ray crystallography, fluorescence-based assays and site-directed mutagenesis to determine the structures and functions of these complexes. For their biophysical characterization we employ isothermal titration calorimetry, ESI-MS, bio-layer interferometry, thermophoresis and CD spectroscopy.
Prof. Dr. Mathias Gautel, King's College London
The laboratory of Mathias Gautel uses molecular genetic, cell biophysical and biophysical, biochemical, structural, and physiological methods to study the biological principles that underpin sarcomere assembly, signaling, and controlled proteolytic turnover. Current areas of interest include mechanosignalling by muscle cytoskeletal proteins, their cross-talk with the proteolytic systems of muscle and gene expression regulation, and the perturbation of these processes in acquired and inherited muscle diseases.
“Each of us alone would not have been able to achieve what has now become possible through the interactions of our network. The awarding of Synergy Grants is a smart strategy by the European Research Council to enable the collaboration of leading teams that can complement each other’s research endeavours in a joint project.“
Dr. Frank Schnorrer, Developmental Biology Institute (IBDM) in Marseille
The Schnorrer group uses the Drosophila adult muscles, in particular the flight muscles to image muscle-tendon attachment and myofibrillogenesis in intact developing animals. The scientists have found that myotubes first attach to tendon cells at both myotube tips and only after being stably attached, myofibrillogenesis is triggered throughout the entire muscle. Using in vivo laser cutting experiments the group has discovered that mechanical tension is generated after muscles have attached to tendons. Interestingly, this tension build-up is required for ordered myofibrillogenesis. Novel high-resolution microscopy techniques are applied to monitor myofibril assembly at the nanoscale.
Prof. Dr. Dirk Görlich, Max Planck Institute for Biophysical Chemistry, Göttingen
Using molecular biology and biochemistry methods the group of Dirk Görlich has done pioneering work in the field of nucleocytoplasmic transport with discoveries of importins, exportins, and deciphering the mechanism of nuclear pore transport selectivity. Over the last years, his lab established a highly efficient nanobody discovery workflow and developed nanobodies as imaging tools, crystallization chaperones, intracellular inhibitors, and for therapeutic purposes such as treatment of Covid-19.