Optical tweezers coupled to a confocal fluorescence microscope and microfluidic Flow Cell

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The Rudolf Virchow Center at the University of Würzburg harbors state of the art infrastructure for imaging of biological samples. We can resolve samples ranging from Å resolution, seamlessly moving into the nm range and finally going up into the entire organism. To achieve this highly dynamic resolution range we harbor techniques like x-ray crystallography, cryo-EM, super resolution fluorescence microscopy, atomic force microscopy and confocal microscopy just to name a few. The proposed ultra-high-resolution optical tweezers coupled to a high-performance confocal fluorescence microscope and a 4-way microfluidics laminar flow cell instrument is a unique device that is capable of combining force microscopy using optical tweezers with confocal fluorescence microscopy which is ideal for single molecule analysis and manipulation in real time. It will provide an important new and powerful technique to study the function and mechanisms of proteins/nucleic acid complexes at single molecule resolution in real time and bring our imaging capabilities to the next level. In this proposal we envision to tackle and address several important research projects at the University of Wuerzburg that comprise the processes of RNA metabolism, G4 quadruplexes and nucleotide excision DNA repair. The data delivered by the proposed instrument will significantly enhance our understanding of molecular processes in these different research areas which could otherwise not be realized.