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[Summer series] Pierre-Damien Coureux - Frozen in time

Within École Polytechnique’s Biochemistry Laboratory, Pierre-Damien Coureux uses X-ray crystallography to highlight the flagship role of a protein in the translation of DNA.

©Silvère Leprovost

Cryo-electron cryomicroscopy is going through a period of spectacular growth. This technique serves to preserve macromolecular complexes for observation and study using cold rather than crystallization to fix the specimens. Anticipating the development of this specialty, ten years ago the scientists at École Polytechnique’s Biochemistry Laboratory included the project in their research activities and recruited Pierre-Damien Coureux to direct the research.

An essential discovery in the understanding of the control of cellular processes

Bringing to bear his expertise in structural biology, X-ray crystallography, and transmission cryo-electron microscopy, Pierre-Damien Coureux has evidenced the role of the protein called “aIF2” in the mechanism of translation of the genetic message carried by the DNA. Indeed, DNA is not translated in a single step in the cells; it is initially duplicated in the form of copies called messenger RNAs (mRNAs). The latter are then translated to produce the corresponding proteins. This translation step is itself divided into three steps: initiation, elongation, and termination. Using X-ray crystallography, in 2012 Pierre-Damien Coureux and the researchers at the Biochemistry Laboratory demonstrated the central role of the aIF2 protein in the translation of the genetic message. Since then, their research, relying this time on cryo-electron microscopy, has yielded a detailed description of the role of aIF2 in initiating the synthesis of a protein from the mRNA. The findings were published in 2016 in the journal Nature Communications. Understanding the molecular mechanisms governing this step is particularly important because numerous studies have shown that it is a critical step in controlling many cellular processes: nutrient deprivation response, cell differentiation, synaptic response, or cancerization.

Long and complex results processing

To achieve these results, the researcher has had to adapt to constant refinements in cryo-electron cryomicroscopy techniques. Although the method allows for a thorough preparation of samples, experimenting on international state-of-the-art instruments is not always readily accessible, and processing the results is time-consuming and complex. “None of which is insurmountable,” says Pierre-Damien Coureux. “Our research is constantly progressing but we must be patient and obstinate. Six years elapsed between the preparation of our samples and the publication of our first research findings.” In the future, Pierre-Damien Coureux intends to use the published results to continue a detailed study of this fundamental biological mechanism.

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Find all the portraits of researchers of our summer series, here.

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