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Optical superresolution microscopy of molecular mechanisms of disease

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Key Words: nanoscopy, live cell imaging, neurodegeneration, protein self-assembly reactions

The self-assembly of proteins into ordered macromolecular structures is fundamental to a variety of diseases, for example in neurodegeneration, where misfolded proteins aggregate into toxic fibrillar shapes, or during virus replication, where the assembly of functional virions in the host cell is a tightly organized process. In this talk, I will give an overview of optical imaging techniques (1-3) that allow us to gain insights into protein self-assembly reactions in vitro (4 – 7), in cells (8 – 10), and in live model organisms of disease (11). In particular, we wish to understand how proteins nucleate to form functional or toxic structures and to correlate such information with biological phenotypes. I will show how single molecule localization microscopy, and developments in high speed structured illumination microscopy are capable of tracking the aggregation of proteins in vitro and in vivo, and how such data are interpreted in the context of disease (11-17).

References: (1) F. Stroehl and C.F. Kaminski, Optica (2016) (2) M. Fantham and C.F. Kaminski, Nat. Phot. (2016) (3) F. Stroehl et al., Sci. Rep. (2016) (4) G.S. Kaminski Schierle, et al, JACS (2011) (5) D. Pinotsi et al, Nano Letters (2013) (6) R. Laine et al, Nat. Comms (2018) (7) R. Laine et al, eLife (2018) (8) E. Avezov et al., Nat. Cell Biol.(2018) (9) D. Pinotsi et al, PNAS (2016) (10) M. Lu et al, JBC (2019) (11) G.S. Kaminski Schierle et al, ChemPhysChem (2011) (12) C. Michel, et al, JBC (2014) (13) T. Murakami, et al, Neuron (2015) (14) H. Wong, et al, Neuron (2017) (15) G. Fusco, et al, Nat. Comms. (2016) (16) S. Qamar, et al, Cell (2018) (17) J. Lautenschlaeger et al., Nat. Comms. (2018)

This talk is part of the Engineering - Mechanics and Materials Seminar Series series.

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