From DNA Nanotechnology to biomedical insight: Towards single-molecule spatial omics

Super-resolution fluorescence microscopy is a powerful tool for biophysical and biological research. The transient binding of short fluorescently labeled oligonucleotides (DNA-PAINT) can be leveraged for easy-to-implement multiplexed super-resolution imaging that achieves molecular-scale resolution across large fields of view. This seminar will introduce recent technical advancements in DNA-PAINT including approaches that achieve sub-10-nm spatial resolution and spectrally unlimited multiplexing in whole cells followed by recent developments in novel protein labeling probes that have the potential to facilitate DNA-barcoded labeling of much of the proteome within intact cellular environments. Applications of these new approaches will be discussed in cell surface receptor imaging and neuroscience. Visualization and quantification of cell surface receptors at thus far elusive spatial resolutions and levels of multiplexing yield fundamental insights into the molecular architecture of surface receptor interactions thus enabling the future development of more refined “pattern”-based therapeutics. A key approach in implementing these methods has been to leverage standard off-the-shelf fluorescence microscopy hardware as a tool for spatial omics, thus democratizing the ability to visualize most biomolecules and probe their network-wide interactions in single cells, tissues, and beyond with single-molecule-based "Localizomics”.