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Related Concept Videos

Cryo-electron Microscopy01:28

Cryo-electron Microscopy

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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
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Industrial cryo-EM facility setup and management.

Kasim Sader1, Rishi Matadeen1, Pablo Castro Hartmann1

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Summary
This summary is machine-generated.

The Cambridge Pharmaceutical Cryo-EM Consortium shares lessons learned establishing cryo-electron microscopy (cryo-EM) facilities for drug discovery. Key insights cover site selection, installation, operation, and maintenance of advanced cryo-EM instruments.

Keywords:
cryo-EMfacility managementfacility setupindustry

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Area of Science:

  • Structural Biology
  • Biophysics
  • Drug Discovery

Background:

  • Cryo-electron microscopy (cryo-EM) adoption by industry, especially for structure-based drug design, demands enhanced reliability, reproducibility, and throughput.
  • Technological advancements like direct electron detectors and improved software have accelerated cryo-EM capabilities.
  • The Cambridge Pharmaceutical Cryo-EM Consortium was formed to mitigate risks in exploring cryo-EM for early-stage drug discovery.

Purpose of the Study:

  • To document and share practical lessons learned from establishing multiple high-resolution cryo-electron microscopy facilities.
  • To provide guidance on the critical aspects of setting up and operating cryo-EM infrastructure for industrial applications.
  • To inform future endeavors in building and managing cryo-EM facilities for pharmaceutical research.

Main Methods:

  • The study details experiences from setting up two Thermo Scientific Krios Cryo-EM microscopes for the Consortium and additional Glacios microscopes at member sites.
  • It includes the establishment of a comprehensive cryo-EM facility (eBIC for Industry) at Diamond Light Source, featuring both Krios and Glacios instruments.
  • Lessons learned encompass site evaluation, installation, scheduling, operational procedures, and maintenance of microscopes and preparation labs.

Main Results:

  • Successful establishment of multiple cryo-EM facilities, including Consortium Krios microscopes and industry-focused eBIC for Industry.
  • Identification of critical factors for successful site selection and installation of high-resolution cryo-EM instruments.
  • Development of operational and maintenance strategies to ensure reliability and reproducibility in an industrial setting.

Conclusions:

  • Establishing industrial cryo-EM facilities requires careful planning regarding site infrastructure, instrument installation, and operational workflows.
  • Collaboration, as demonstrated by the Consortium, is vital for sharing risks and expertise in adopting cutting-edge technologies like cryo-EM.
  • Best practices in operation, maintenance, and image processing are essential for maximizing the impact of cryo-EM in drug discovery.