Research

Molecular Imaging and Bionanotechnology

Visualizing Molecular Complexity with Single-Molecule Precision

Cells are densely packed molecular environments where thousands of proteins, RNAs, and other biomolecules interact in highly organized and dynamic ways. Unraveling this complexity requires imaging tools that combine nanometer-scale resolution with molecular specificity and high multiplexing capacity. Our research group, Molecular Imaging and Bionanotechnology, develops and applies precisely such tools, with the goal of revealing biological systems at unprecedented spatial detail.

At the core of our efforts is DNA-PAINT, a super-resolution microscopy technique we developed that enables quantitative, single-molecule localization of target molecules in cells. DNA-PAINT relies on the transient binding of dye-labeled “imager” strands to complementary “docking” strands conjugated to the target of interest. This interaction is programmable through DNA sequence design, allowing us to fine-tune binding kinetics and systematically exchange imagers in a process we call Exchange-PAINT. This approach enables multiplexed imaging of dozens to hundreds of targets within the same specimen.

Building on this foundation, we introduced RESI (Resolution Enhancement by Sequential Imaging), a breakthrough strategy that pushes the spatial resolution of fluorescence microscopy into the Ångström regime. By imaging the same protein multiple times with uniquely barcoded antibodies and computationally combining localizations, RESI achieves sub-nanometer precision in situ, bridging the gap between structural biology and cell biology.

In parallel, we developed SUM-PAINT, which enables imaging of a large number of targets in a single sample by leveraging speed improvements in multiplexing. Together, these innovations make DNA-PAINT a powerful and scalable platform for spatial proteomics, capable of mapping the nanoscale architecture of molecular networks in intact cells and tissues.

Our research spans both fundamental and translational applications. We use DNA-PAINT to investigate how membrane receptors – such as immune checkpoint molecules – are spatially organized and how this organization relates to cellular function and therapeutic response. We also apply our methods to profile molecular patterns in disease contexts, including cancer and neurodegeneration, and explore their use in biomarker discovery and diagnostic imaging.

Beyond imaging, we harness the programmability of DNA Nanotechnology to create self-assembling scaffolds, standardized barcodes, and modular reagents that facilitate probe design, signal amplification, and quantitative readout.

Altogether, our vision is to provide the tools and frameworks needed to generate comprehensive molecular maps of cells – with single-molecule precision, high multiplexing, and direct biomedical relevance.