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Untangling Neurodegenerative Diseases using Cryo-Electron Microscopy  

Wednesday, February 7, 2018


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Protein aggregation is a hallmark of many neurodegenerative diseases, including Alzheimer’s and Parkinson’s. However, the mechanisms linking aggregation to neurotoxicity remain poorly understood, partly because only limited information is available on the structure of these aggregates. Determining the atomic structures of these aggregates is crucial to understanding their formation, clearance and spread in the human body.

Furthermore, very little is known about the native structure of protein aggregates inside cells. This challenge is addressed utilizing the latest developments in cryo-electron tomography (cryo-ET). Thin lamellas of vitrified cells containing protein aggregates are prepared by cryo-focused ion beam (cryo-FIB) and subsequently imaged in three dimensions by cryo-ET.

During this webcast, we will explain how using cryo-EM to solve the structures to 3.4 Angstrom resolution of amyloid fibrils isolated from post-mortem brain tissue of patients with a range of neurological disorders can elucidate the molecular and structural basis of neurodegeneration. Additionally, we will show how cryo-ET allows for the analysis of aggregate structures within pristinely preserved cellular environments at molecular resolution to shed new light on the cellular mechanisms of neurodegeneration.

In this webcast, attendees will learn:

  • About advances in cryo-TEM single particle analysis (SPA) for structure determination of protein complexes.
  • How cryo-EM/SPA was applied to determine the first near-atomic resolution of filaments.
  • The importance of atomic cryo-EM filament structure for drug design and the development of biomarkers for early detection.
  • The technological developments that allow high-resolution imaging of the cell interior by cryo-ET.
  • The importance of determining the structure of protein aggregates in situ, i.e. within an intact cellular environment.
  • How cryo-ET imaging of protein aggregates within cells illuminates their mechanisms of cytotoxicity.

This webcast has been produced on behalf of the sponsor who retains sole responsibility for content. About this content

Anthony Fitzpatrick
Assistant Professor of Biochemistry and Molecular Biophysics
Zuckerman Institute, Columbia University
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Rubén Fernández-Busnadiego
Project Group Leader
Max Planck Institute of Biochemistry in Martinsried, Germany
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Dr. Jayshan Carpen
Springer Nature
View Biography

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