Confocal microscope

• Subject Area: Medicine
• Term: Funded in 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 450557679

Cystic fibrosis (CF) caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains the most common fatal genetic disease in Caucasian populations. In the Cystic fibrosis lung, CFTR dysfunction causes dehydration and acidification of airway surfaces, leading to abnormal viscoelastic properties of the mucus and impairs important airway defence functions such as mucociliary clearance and bacterial killing. These defects trigger a pathogenetic cascade of mucus plugging, chronic neutrophilic inflammation, infection and progressive structural lung damage that that remains the main cause of death in patients with CF.In the context of our research on CF and other chronic progressive lung diseases, we will use confocal microscopy to visualize the architecture of the airway mucus and the differential expression of mucins as well as to measure mucus permeability by tracking the motion of fluorescently tagged model particles. Confocal microscopy is the standard method to measure airway surface liquid height. Furthermore, confocal microscopy will allow us to track the diffusion of drugs and particles into and within mucus layers as well as to measure protease activity using fluorescence resonance energy transfer sensors. Therefore, the requested confocal microscope will be vitally important for our basic and translational work on understanding the pathogenesis of CF and the development of novel therapies for this severe genetic condition. The microscope will be integrated in the research infrastructure of the Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin. Additionally, the microscope will be used in research collaborations at the Charité - Universitätsmedizin Berlin and with other partners of the Berlin University Alliance, many of whom participate in the Collaborative Research Centre “Dynamic Hydrogels at Biointerfaces”.The requested instrument is a versatile high-end confocal microscope additionally equipped with standard wide-field fluorescence, providing a flexible assay platform for fast, precise, high-resolution imaging in confocal and in wide-field mode. The performance class of the requested instrument is tailored toward multiple research needs, including environmental control, a white light laser for multi-channel imaging and super-sensitive detectors allowing for flexible spectral environment, as well as enabling fluorescence recovery after photobleaching and fluorescence correlation spectroscopy imaging. It is equipped with a high precision scanning stage, autofocus and high-frequency camera to screen samples rapidly in wide-field or in confocal mode, or even combining the two imaging methods.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Konfokalmikroskop
• Instrumentation Group: 5090 Spezialmikroskope
• Applicant Institution: Charité - Universitätsmedizin Berlin
• Leader: Professor Dr. Marcus Mall