2D/3D STED microscope (renewal))

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 576998009

The requested renewal of the 2D/3D STED microscope is essential to meet current and future scientific demands across a broad spectrum of biomedical and interdisciplinary research. Numerous projects rely on lateral resolution below 30 nm and isotropic 3D reso-lution down to 50 nm to resolve subcellular and sub-organelle structures such as dendritic spines (~100 nm), synaptic clefts (~50 nm), active zones in presynaptic terminals, t-tubules in cardiac myocytes, and intra-protein domains. These structures are either inac-cessible or only partially resolved using diffraction-limited microscopy, making state-of-the-art STED indispensable. High-performance adaptive optics are essential for maintaining super-resolution in thick, optically heterogeneous tissues such as adult brain slices, cardiac muscle, and organoids. Aberrations caused by light scattering significantly impair image quality; real-time correc-tion ensures that imaging can be performed reliably across a wide range of biological contexts—including studies of extracellular matrix (ECM) structure, cardiac fibrosis, and synaptic organisation in neurodevelopmental disorders. Live-cell super-resolution imaging is another critical requirement. Advanced illumination strategies that dynamically adjust excitation and depletion doses help minimise photo-bleaching and phototoxicity, enabling long-term observations of dynamic cellular pro-cesses. This is particularly critical for experiments involving sensitive specimens such as neurons, epithelial monolayers, organoids, and immune cells. These functions are indis-pensable for tracking synaptic plasticity, actin dynamics, vesicle trafficking, and matrix remodelling in real time. Advanced fluorescence lifetime imaging (FLIM) capabilities are also essential. Several pro-jects require lifetime-based quantification of membrane tension, molecular crowding, con-formational changes, or metabolic shifts (e.g. NAD+/NADH ratios). This adds a functional dimension to the structural information provided by super-resolution microscopy and is crucial for addressing key questions in neurobiology, immunology, and mechanobiology. Collectively, the eight scientific supplements outline over twenty research projects—ranging from neuroscience and cardiology to infection biology and tissue engineering—that depend on a multi-laser, multi-colour, deep-penetration super-resolution microscope with integrated live-cell and lifetime imaging capabilities. Many of these projects involve thick tissue, multi-parameter imaging, or dynamic measurements that are not possible with standard confocal systems or older-generation STED setups. The proposed upgrade is essential to support the current user base and fully realise the scientific potential of these diverse projects.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: 2D / 3D STED Mikroskop (Erneuerung)
• Instrumentation Group: 5090 Spezialmikroskope
• Applicant Institution: Friedrich-Alexander-Universität Erlangen-Nürnberg
• Leader: Dr. Ralf Palmisano