Achieving Ångström-resolution fluorescence microscopy with off-the-shelf hardware and reagents

November 7, 2024
2:00 PM ET / 1:00 PM CT / 11:00 AM PT / 7:00 PM GMT

Duration: 1 hour

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Summary

This webinar will demonstrate a DNA-barcoding method, resolution enhancement by sequential imaging (RESI), that improves the resolution of fluorescence microscopy down to the Ångström scale using off-the-shelf fluorescence microscopy hardware and reagents. By sequentially imaging sparse target subsets at moderate spatial resolutions of >15 nm, we show that single-protein resolution can be achieved for biomolecules in whole intact cells.

Furthermore, we experimentally resolve the DNA backbone distance of single bases in DNA origami with Ångström resolution. We use our method in a proof-of-principle demonstration to map the molecular arrangement of the immunotherapy target CD20 in situ in untreated and drug-treated cells, which opens possibilities for assessing the molecular mechanisms of targeted immunotherapy.

These observations demonstrate that, by enabling intramolecular imaging under ambient conditions in whole intact cells, RESI closes the gap between super-resolution microscopy and structural biology studies and thus delivers information critical to understanding complex biological systems.

Speakers:

Ralf Jungmann
Title: Professor and Chair, Molecular Physics of Life at Ludwig Maximilian University, and
Max Planck Fellow, the Max Planck Institute of Biochemistry

Ralf Jungmann holds the chair for Molecular Physics of Life at LMU and is a Max Planck Fellow at the MPI of Biochemistry. Jungmann studied physics at Saarland University and received a PhD from TUM and was a postdoc at Harvard University. Jungmann is recognized for his developments and applications of DNA-PAINT and DNA Nanotechnology. DNA-PAINT is a super-resolution microscopy technique that uses short, transient DNA-DNA interactions to provide unrivaled resolution and multiplexing.

The method has unlocked potentials in diverse realms, from unraveling intricate biological processes at the molecular level to aiding advancements in material science and biomedicine. In two of their latest studies, Jungmann and his team achieved Ångström-resolution fluorescence microscopy and spatial proteomics at single protein resolution in neurons, unravel the Mode of Action of antibodies in cancer in the first study and uncovering a novel type of synapse in the latter. Jungmann is also co-founder of two startup companies (Ultivue and Massive Photonics).

Achieving Ångström-resolution fluorescence microscopy with off-the-shelf hardware and reagents

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