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Molecular Basis for Protein Synthesis by the Ribosome

Molecular Basis for Protein Synthesis by the Ribosome

DEPARTMENT

Integrated structural biology

TEAM LEADERS

Gulnara YUSUPOVA

Marat YUSUPOV

The ribosome is a giant ribonucleoprotein cellular assembly that translates genetic code into protein in all living organisms. Alterations in diverse range of translational machinery cause an extensive and growing catalogue of human diseases. Given the central role of the ribosome in the cell, living organisms have elaborated defense strategies producing chemical substances as for example antibiotics in case of bacteria, to impair ribosome functions in other organism by inhibiting different stages of protein biosynthesis. That is why the ribosome is one of the main antibiotic targets in the cell. More than 40% of clinically useful antibiotics target the ribosome apparatus. Similarly, the eukaryotic ribosome is a major target for small-molecules inhibitors produced as secondary metabolites by bacteria, fungi and plants.


The overall goal of our research is to gain structural insights into the mechanism of protein synthesis by the ribosome, and the mode of action of ribosome-targeting inhibitors. For this, our group are working with both X-ray crystallography as well as cryo Electron Microscopy. We have developed methods for studying the bacterial 70S ribosome from the extreme thermophilic microorganism Thermus thermophilus as well as for the 80S ribosome from the yeasts Saccharomyces cerevisiae and Candida albicans, which we trap at different steps of protein biosynthesis or in complex with inhibitors/antibiotics and determine their structures.

Current projects

  • High-resolution structures of the prokaryotic 70S and eukaryotic 80S ribosome trapped at different stages of protein synthesis.
  • High-resolution structures of prokaryotic and eukaryotic  ribosomes, including the ribosomes from pathogenic organisms, in complex with antibiotics
  • Structure determination of the human ribosome and its functional complexes.

Research subgroup(s)

Members

Researchers

Post-doctoral fellows

Collaborations and networks

  • Christopher D. Vanderwal, Department of Chemistry, University of California, Irvine, USA
  • Scott Blanchard, Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, USA
  • Armin Wagner, Dimond Light Source, UK - the long-wavelength MX beamline, UK
  • Albert Guskov, Biomolecular X-ray Crystallography Lab, University of Groningen, Netherlands
  • Greg Challis, Department of Chemistry, University of Warwick, UK
  • Konstantin Usachev,Laboratory of Structural Biology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia. 
  • Shamil Validov, Institute of Biology, Russian Academy of Sciences, Kazan, Russia

Funding and partners

  • FRM grant: ”Mechanism of readthrough and stop codon recognition and its failures”, 2019-2021
  • NIH grant: “X-ray study of the lissoclimide family anticancer drugs on the ribosome, 2019-2022

News

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Nemanja Milicevic, winner of "les Grandes Avancées Françaises en Biologie" award from the Academy of Sciences

This award aims to highlight young researchers, who are the first authors of published articles, by offering them the opportunity to be presented by…

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Awards and recognitions

  • Gulnara YUSUPOVA - Chevalier de la Légion d'honneur - Etat français - 2017
  • Gulnara Yusupova - Member of the European Molecular Biology Organization (EMBO) - EMBO - 2016
  • Gulnara YUSUPOVA - Research prize - INSERM - 2013
  • Gulnara YUSUPOVA - Gregori Aminoff Prize - Académie royale suédoise des sciences - 2012
  • Gulnara YUSUPOVA - Newcomb Cleveland prize - The American Association for the Advancement of Science – 2001
  • Marat YUSUPOV - Silver medal - CNRS - 2012
  • Marat YUSUPOV - Program grant - Human Frontier Science Program (HFSP) - 2012
  • Marat YUSUPOV - Gregori Aminoff Prize - Académie royale suédoise des sciences - 2012
  • Marat YUSUPOV - Emile Jungfleisch Prize - Institut de France de l'Académie des Sciences - 2011
  • Marat YUSUPOV - ERC Advanced grant - European Research Council (ERC) - 2011
  • Marat YUSUPOV - Member of the European Molecular Biology Organization (EMBO) - EMBO – 2009
  • Marat YUSUPOV - Prix Newcomb Cleveland - The American Association for the Advancement of Science – 2001

Publications

Integrated structural biology