Structural Biology and Chemistry

Observing life at atomic level because chemistry is the motor of life. Researchers in the Department of Structural Biology and Chemistry study the three-dimensional organization and properties of molecules of biological interest.

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The structure of a molecule is intricately linked to its function. The 11 laboratories in the Department of Structural Biology and Chemistry focus their research on the three-dimensional organization, properties, synthesis and molecular action of molecules of biological interest, especially those that play a role in human diseases. This research reveals information that is vital for developing strategies to interfere with these processes and to develop new therapeutic, diagnostic and vaccine strategies.

 

The 7 biology research units of the department study the proteins and nucleic acids playing a key role in human pathology by using structural, analytical, biophysical, proteomics, and bioinformatics approaches. The 4 chemistry units focus on the synthesis of molecules of biological interest and chemical probes to study and interfere with the molecular mechanisms aberrant in disease. The chemists have expertise in nucleosides and nucleic acids chemistry and applications, in peptides, glycans and bioconjugates, medicinal chemistry and drug design, and in chemical biology (fluorescent and bio-orthogonal probes). In collaboration with the other departments and the Institut Pasteur International Network, the Department of Structural Biology and Chemistry works on bacterial, parasite and viral infections, on neurological diseases and cancer.

Cross-disciplinary expertise on the campus

The projects specifically focus on the characterization at the molecular level of biological molecules and their interactions by using cross-disciplinary expertise and complementary approaches spanning organic chemistry, chemical biology, biophysics, biochemistry, cell biology and structural biology. The objects of this research are at the level of the individual molecules, protein complexes, the cell organelles, the proteomes and the entire cell. Structural studies are conducted to characterize proteins and nucleic acids, their interactions in the biological context or in cells, the mechanisms of action of drugs and their targets. The technologies employed for this aim include X-ray crystallography, electron cryo-microscopy, NMR, and mass spectrometry. The experimental approaches are complemented by a range of computational approaches to simulate and predict the function of complex biological systems.

Titan KriosTM, the centerpiece of the nanoimaging initiative

The most impressive tool in the department is the Titan KriosTM 300 kV electron microscope, delivered in 2017. This microscope, the most powerful in the world, could be purchased by the Institut Pasteur with the help of major government funding and the generosity of the general public. Its purpose is the determination of atomic resolution 3D structures of proteins and complexes without crystallization, and, with unprecedented detail the characterization of the structure of cellular components in the cell. The Titan KriosTM is the centerpiece of the nanoimaging initiative, a core facility with three additional electron microscopes that are being installed during 2019, used for sample preparation and screening of conditions.

 

The research projects of laboratories in all departments are supported by technological platforms and core facilities for protein production, antibody engineering, proteomics, biophysics, NMR, X-ray, and cryoEM. Their role is not limited to providing service, but they form an active part of the scientific life of the department.

 

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Michael Nilges,

Director of the Department of Structural Biology and Chemistry

The structure of a molecule is intricately linked to its function. This is why, by observing molecules at atomic level, we can explain the bases of life and understand the interactions between cells. Thanks to this in-depth knowledge, it becomes possible to rationally design drugs.

 

 

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