Venue: Centre Broca
Henning Stahlberg
Henning Stahlberg, Laboratory of Biological Electron Microscopy, Institute of Physics, School of Basic Sciences, Federal Institute of Technology Lausanne (EPFL),
Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Switzerland.
Invited by François Ichas
Title
Investigating Neurodegeneration in alpha-Synucleinopathies with Cryo-Electron Microscopy
Abstract
Cryo-transmission electron microscopy (cryo-EM) or tomography (cryo-ET) of frozen hydrated specimens is an efficient technique for analyzing the structure of proteins or tissue sections. We study human brain tissue from patients who died from Parkinson’s disease or Alzheimer’s disease, using high-pressure freezing, sectioning and cryo-ET, as well as correlative light and electron microscopy (CLEM). We also study alpha-synuclein fibrils, which is the protein underlying Parkinson’s disease, multiple system atrophy (MSA) and Dementia with Lewy bodies (DLB). Different fibril polymorphs will be presented and their potential impact on intracellular neurodegeneration mechanisms discussed.
Cryo-EM and cryo-ET suffer from a signal-to-noise ratio or recorded images. Contrast of cryo-EM can be improved through diffractive imaging. We employ a 4D-scanning transmission electron microscopy approach with parallax or ptychography data processing, using an aberration-corrected Titan Krios. This 4D-STEM approach shows improved contrast of cryo-EM images.
- Burger et al., 1.94 Å structure of synthetic α-synuclein fibrils seeding MSA neuropathology, bioRxiv 2024.07.01.601498;
doi: https://doi.org/10.1101/2024.07.01.601498 - Shahmoradian et al., Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes. Nature Neuroscience 22, 1099-1109 (2019)
https://www.nature.com/articles/s41593-019-0423-2 - Küçükoğlu et al., Low-dose cryo-electron ptychography of proteins at sub-nanometer resolution. Nature Commun. 15, 8062 (2024).
https://doi.org/10.1038/s41467-024-52403-5
Biosketch
Prof. Henning Stahlberg’s research focuses on high-resolution cryo-electron microscopy techniques to study neurodegenerative diseases and other protein systems. He has contributed to the development of electron microscopy hardware and applications, sample preparation, data collection schemes, and data analysis software systems. His team uses cryo-electron microscopy including 4D-STEM to study brain tissue from patients with Parkinson’s disease and other neurodegenerative conditions, as well as the molecules involved in these diseases.