Prof. Dr. Enrico Klotzsch

Prof. Klotzsch erforscht, wie mechanische Kräfte und physikalische Belastung neurodegenerative Erkrankungen auslösen oder verschärfen — konkret untersucht er, wie Varianten des Proteins FUS unter mechanischem Stress ihr Verhalten in der Zelle verändern, sich fehlerhaft ansammeln und die Kernporen-Komplexe stören. Dazu nutzt er hochauflösende Mikroskopie und automatisierte Bildanalyse, um diese Prozesse auf Ebene einzelner Zellen und Moleküle sichtbar zu machen. Die Erkenntnisse könnten Ansätze für Diagnostik und Therapie neurodegenerativer Erkrankungen wie ALS eröffnen, wo mechanische Faktoren bislang unterschätzt werden.

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• Der Einfluss von Mechanischen Kräften in Neurodegenerativen Krankheiten

  Quelle ↗

  We will use live-cell and super-resolution microscopy combined with automated image processing to determine the impact of large numbers of FUS variants on the sub-cellular distribution, nuclear re-localisation and aggregate formation at a single cell and molecule level under the impact of shock and external forces. The changed interaction between nuclear pore complex and FUS variants will be evaluated, therefore we aim to use 2 color super-resolution microscopy for structural changes and fluorescence resonance energy transfer (FRET) to study temporal changes in FUS transport across the nuclear membrane. Bioinformatic analysis will integrate findings across FUS variants and experiments.

• NMR and EPR reveal a compaction of the RNA-binding protein FUS upon droplet formation

  2021

  Nature Chemical Biology · DOI

• Temporal analysis of T-cell receptor-imposed forces via quantitative single molecule FRET measurements

  2021

  Nature Communications · DOI

  Mechanical forces acting on ligand-engaged T-cell receptors (TCRs) have previously been implicated in T-cell antigen recognition, yet their magnitude, spread, and temporal behavior are still poorly defined. We here report a FRET-based sensor equipped either with a TCR-reactive single chain antibody fragment or peptide-loaded MHC, the physiological TCR-ligand. The sensor was tethered to planar glass-supported lipid bilayers (SLBs) and informed most directly on the magnitude and kinetics of TCR-imposed forces at the single molecule level. When confronting T-cells with gel-phase SLBs we observed both prior and upon T-cell activation a single, well-resolvable force-peak of approximately 5 pN and force loading rates on the TCR of 1.5 pN per second. When facing fluid-phase SLBs instead, T-cells still exerted tensile forces yet of threefold reduced magnitude and only prior to but not upon activation.

• Localized detection of ions and biomolecules with a force-controlled scanning nanopore microscope

  2019

  Nature Nanotechnology