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Visualizing the Architectures of Beta-Sheet Assemblies and Biomolecular Condensates using Single-Fluorogen Orientation-Localization Microscopy

by Micron School of Materials Science & Engineering

Academic Seminar

Wed, Apr 2, 2025

3 PM – 4 PM MDT (GMT-6)

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Join the Quantum DNA group within the Micron School of Materials Science and Engineering as they welcome Matthew Lew from the University of Washington. Lew will discuss Single-molecule orientation-localization microscopy (SMOLM) combines super-resolved localization microscopy (SMLM) with blinking fluorescent molecules to measure fluorophores’ 3D positions and 3D orientations simultaneously with nanoscale resolution. Lew's group has pioneered the use of fluorogenic probes, i.e., fluorophores light up in suitable chemical and viscoelastic environments, with SMOLM to characterize the organization of biomolecular assemblies without covalently modifying the molecules themselves. We used the transient binding and blinking of Nile red to quantify the helical structure of fibrils of the designed amphipathic peptide KFE8 and the pathological amyloid-beta peptide Aβ42. They have also deployed Nile blue, Nile red, and merocyanine 540 to study environmental and structural
features within biomolecular condensates formed by proteins with intrinsically disordered regions. Our experiments show that fluorogenic probes are a powerful complement to conventional labeling techniques for elucidating the dynamic architectures of biomolecular assemblies.

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Matthew Lew

Washington University

Matthew Lew joined Washington University in 2015. Before arriving in St. Louis, he was a postdoctoral fellow in the de la Zerda Group at the Stanford University School of Medicine. He earned his PhD in Electrical Engineering working in the laboratory of W. E. Moerner, a co-recipient of the Nobel Prize in Chemistry 2014 for “the development of super-resolved fluorescence microscopy.” Professor Lew is a recipient of a 2017 NSF CAREER Award, an Excellence in Teaching Award from Emerson Electric Co. and an Outstanding Faculty Award from the WashU Graduate Student Senate. Professor Lew is a senior member of Optica (formerly OSA) and the faculty advisor of Washington University SPECTRA, a student chapter of Optica and SPIE.

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Co-hosted with: College of Arts and Sciences

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