81 80 Principal Scientist Profiles Christian Franke Christian Franke Principal Scientist Profiles JUNIOR-PROFESSOR (WITH TENURED TRACK) FOR DIGITIZED EXPERIMENTAL MICROSCOPY Christian Franke holds a PhD from the University of Würzburg working with Prof. Markus Sauer on the development of methods for quantitative superresolution microscopy (SRM). In 2017 he joined the MPI of Molecular Cell Biology and Genetics in Dresden as a postdoctoral fellow in the department of Prof. Marino Zerial, focusing on the application of SRM to cell biological questions, specifically endosomal trafficking. End of 2020, he started his own research group at FSU as a Professor for Digitized Experimental Microscopy. He is a member of the Abbe Center and School of Photonics, the Jena Center of Soft Matter, member of the Studies Affairs Committee and Board of Examiners of the international“Medical Photonics”Master program and the Co-Organizer of the “Physikalisches Kolloquium”. CHRISTIAN FRANKE RESEARCH AREAS • Super-Resolution Microscopy methods development (Localization Microscopy for highest spatial resolution, Structured Illumination Microscopy for in vivo imaging) • Super-Resolution Microscopy application in life and material sciences • Computational Microscopy • Application to cellular trafficking (e.g. endocytosis) • High-Fidelity optical 3D Scanning with Structured Illumination • High-Resolution multi-scale optical measurement of living systems TEACHING FIELDS Main teaching activities lay in the international Master of Medical Photonics program lectures & according seminars in Physical Optics and Optical Engineering – these lectures are also open to Master students in Physics and Photonics. Additionally, Prof. Franke established an advanced practical module in “Applied Super-Resolution Microscopy” for Master of Physics students. Since 2024, he is also active in teaching physics to students of medicine & dentistry in lectures and practical courses. RESEARCH METHODS • Quantitative Single-Molecule Localization Microscopy, e.g. dSTORM, PALM, (DNA-) PAINT • Random Pattern Structured Illumination (Speckle-SIM) • 3D super-resolution microscopy by PSF engineering, wave-field measurements & computational approaches • AI-based data & image analysis (ML-based image segmentation & multiplexing, Computational Phenotyping) • Various applications of SRM to cell biology & clinical research, as well as nanoparticles-based drug delivery • Quantitative 3D stereophotogrammetry for scanning of whole animals (e.g. mouse models) RECENT RESEARCH RESULTS Seeing is believing. The newly established Franke research group is focused on the development of advanced optical and computational tools for the quantitative study of biological and clinical questions. On one side, we work to advance super-resolution microscopy methods like single-molecule localization microscopy (SMLM, e.g. dSTORM, PALM) and random structured illumination microscopy (nanoSpeck3D) to quantitatively study the structure-function relationship of sub-cellular (trafficking) organelles, e.g. endosomes, with three-dimensional nanometer resolution. Fpr this, we create novel hard- and software tools. Recent efforts to push the limits of 3D volume, colour and time resolution, include the development of quantitative tools for novel 3D SMLM approaches [1-3], correlative multi-colour SMLM and volumetric electron tomography (superCLEM)[4] and their application to cell-biological questions [3, 4-6]. For example, we could visualize for the first time the molecular escape of mRNA molecules, delivered by lipid nanoparticles from endosomal recycling tubules at the nanometer scale with multi-colour dSTORM [5] and help to understand part of the fine-structure in developing liver tissue [6]. Led by our excellent postdoctoral researcher, Dr. Andreas Stark, we recently branched out into macroscopic measurements of 3D volumes by high-fidelity stereophotogrammetry also utilizing structured illumination, with which we can now measure objects on the centimeter to micrometer scale, thus bridging dimensions between the macro- and nanoscopic world. Using this approach, we contributed identifying the intricate relationship between the visual and tactile cortex of mice [7]. We also found a novel way of performing macroscopic 3D measurements with a monocular, miniaturized structured-illumination system [8], which completes our array of optical tools to probe life across 9 orders of magnitude. SINGLE-MOLECULE LOCALIZATION MICROSCOPY AS TOOL IN DRUG DEVELOPMENT In recent years, nanoparticles (NPs) as delivery vehicles for therapeutic cargo, such as small sized DNAs and RNAs, amongst others, have emerged as potentially powerful therapeutics. An increasing number of RNA-based therapeutics have proven effective for clinical treatment. More recently, optimization of chemical and physical properties of NPs have focused the attention on mRNA-based therapeutics, e.g. in the context of vaccines. Major improvements towards clinical application have come from chemical modifications of therapeutics that increase stability and reduce immunogenicity. Nevertheless, efficacy remains a crucial challenge due to limited or poor delivery. Using multi-colour dSTORM we investigated how lipid nanoparticles (LNPs, magenta) are trafficked inside cells and how they deliver their cargo, e.g. mRNA or pharmaceuticals, with nanometer resolution. For the first time, we could visualize their intracellular fate in never-seen detail and could unravel a new way of cargo delivery/ escape via transferrin-positive recycling tubules (green), pointing towards optimized designs for future NPs. [1] Franke et al., Nat. Methods 14, 41-44, (2017). [2] Franke et al., Nat. Methods 15, 990-992 (2018). [3] Franke et al., Commun. Biol. 5, 218 (2022). [4] Franke et al., Traffic 20, 601– 617 (2019). [5] Paramasivam et al. , J. Cell Biol. 221, e202110137 (2022). [6] Belicova et al., J. Cell Biol. 220, e202103003 (2021). [7] Weiler et al., bioRxiv11.04.515161 (2022). [8] Stark et al., Light: Advanced Manufacturing 3, 34(2022). Contact: Phone: + 49 3641 9-47112 Email: christian.franke@uni-jena.de
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