Postdoctoral Researcher in Cryo-EM Method Development for Drug Discovery

Postdoctoral Researcher in Cryo-EM Method Development for Drug Discovery

SOLEIL Synchrotron

Saint-Aubin, France

Position Description:

We are seeking a highly motivated and skilled postdoctoral researcher to join our collaborative project between Servier and the Synchrotron SOLEIL. The successful candidate will focus on advancing cryo-electron microscopy (cryo-EM) technology for drug discovery applications by developing new enabling technology approaches to tackle size limitation in cryo-electron microscopy (cryo-EM). The successful candidate will also develop workflows for optimized sample preparation and data acquisition, utilizing a state-of-the-art Titan Krios G4 microscope equipped with a Falcon 4i and Selectris X energy filter, and Glacios 2. This project involves both methodological advancements in sample preparation and data analysis, and will make targets, with significant pharmaceutical relevance and unmet patients need, accessible for SBDD. The project will be structured around two major research areas with the goal of producing publishable research results:

Cryo-EM Technology Development:

The postdoc will contribute to the development and implementation of workflows aimed at overcoming protein size limitations in cryo-EM by rigidified modular protein imaging scaffolds that bind specifically to drug discovery targets of interest which are unsuitable for X-ray crystallography or too small for traditional high-resolution cryo-EM. These scaffolds form higher molecular weight complexes, improving visibility in cryo-EM and aiding in particle alignment during image processing.

Sample Preparation and Data Collection Optimization:

This research area focuses on optimizing grid preparation strategies to improve sample quality and data acquisition efficiency. This includes refining freezing techniques, minimizing surface effects, and automating data collection processes.

Required Skills & Qualifications:

  • PhD in structural biology, biophysics, biochemistry, or a related field;
  • Demonstrated expertise in single-particle cryo-EM, including grid preparation, sample optimization, and data acquisition;
  • Proficiency with cryo-EM software for data processing and analysis;
  • Experience working with challenging protein targets, such as membrane proteins and protein complexes, experience with antibody-antigen interaction advantageous;
  • Ability to work both independently and collaboratively within an interdisciplinary team;
  • Excellent communication, problem-solving, and collaboration skills.

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