Laserscanning Mikroskop für Temperatursprung-Experimente

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 423465882

The Ebbinghaus group is interested in studying how cells keep their biomolecules folded in space (i.e. spatially inside mammalian cells) and time (i.e. age-dependent changes). The group investigates how physicochemical factors (such as crowding, confinement, hydration) or biological factors (such as chaperones, cell stresses) modulate biomolecular fold and function. Therefore, the group studies biomolecules in different environments ranging from the test tube to the organism. The requested instrument combines high-speed confocal imaging and infrared laser-induced temperature jumps to spatio-temporally resolve biomolecular stability and kinetics directly in cellular environments. To build the instrument, a confocal microscope will be acquired and equipped with an infrared laser to allow for fast and spatially resolved heating of the sample. The instrument will be used in three research projects. In the first project, different biosensors based on specific mutants of the protein barnase are used to quantify the capacity of cells to keep their proteome folded over space and time. In the second project, the requested instrument is used to measure the localization and folding of pathogenic mutants of the protein SOD1 in cells. Further, the effect of intracellular targeted chemical chaperones as new therapeutics against ALS is tested. The third research objective is to extend the current view of how proteins unfold, misfold and aggregate in cells to include liquid-liquid phase separation processes. The insights will potentially redefine the functional role of LLPS in cells in health and disease conditions.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Laser scanning microscope for fast relaxation imaging
• Instrumentation Group: 5090 Spezialmikroskope
• Applicant Institution: Technische Universität Braunschweig
• Leader: Professor Dr. Simon Ebbinghaus