Marat Yusupov
Biography
Marat Yusupov is an Emeritus research director at the CNRS (French National Centre for Scientific Research) and is based at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) in Strasbourg, France. With over 40 years of experience in molecular biology, his research focuses on protein translation and ribosome structure, particularly using structural biology methods to uncover the mechanisms of translation across different domains of life.
He received his higher education diploma from Kazan State University (Russia), followed by a PhD under the supervision of Professor Alexander Spirin at the Institute of Protein Research and Moscow State University. His postdoctoral research was conducted at the same institute in the groups of Professor Spirin and Dr. M. Garber, as well as at the University of California, Santa Cruz (USA), and in France at the Institute for Molecular and Cellular Biology (IBMC) of the University of Strasbourg. After several positions in France and the United States, he was appointed as CNRS research director in 2000 and became a member of the French Academy of Sciences in 2023.
Dr. Yusupov’s scientific achievements include over 100 publications and major contributions to the structural understanding of ribosomes from bacteria1, 2, yeast3, and human pathogens4, as well as higher eukaryotes 5. In recent years, he has led a research group at IGBMC focused on structural biology approaches, including X-ray crystallography and cryo-electron microscopy. His current work explores large ribosomal complexes with a new focus on cryo-electron tomography. This USIAS project exemplifies a shift towards more interdisciplinary collaboration to understand the molecular mechanisms of hibernation.
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1. Khusainov I, et al. (2020) Mechanism of ribosome shutdown by RsfS in Staphylococcus aureus revealed by integrative structural biology approach. Nat Commun 11(1):1656.
2. Yusupov MM, et al. (2001) Crystal structure of the ribosome at 5.5 A resolution. Science 292(5518):883-896.
3. Ben-Shem A, et al. (2011) The structure of the eukaryotic ribosome at 3.0 A resolution. Science 334(6062):1524-1529.
4. Zgadzay Y, et al. (2022) E-site drug specificity of the human pathogen Candida albicans ribosome. Sci Adv 8(21):eabn1062.
5. Nurullina L, Terrosu S, Myasnikov AG, Jenner LB, & Yusupov M (2024) Cryo-EM structure of the inactive ribosome complex accumulated in chick embryo cells in cold-stress conditions. Febs Lett 598(5):537-547.
Fellowship 2025
Dates - 01/12/2025-30/11/2027
Project summary
RIBOSOME TETRAMERS IN CHICK EMBRYOS: A STUDY OF THE FUNDAMENTAL MECHANISMS OF HIBERNATION
Protein synthesis is one of the most energy-demanding cellular processes, and its regulation is essential during stress and developmental transitions. One key mechanism is ribosome hibernation, where ribosomes enter a dormant state to conserve resources. While well-characterized in bacteria and yeast, the structural basis of ribosome hibernation in higher organisms remains poorly understood. This project focuses on Gallus gallus embryos, where ribosomes have been observed forming tetrameric assemblies in response to cold stress.
These ribosome tetramers, arranged into crystalline sheets, most likely play a role in protecting the protein synthesis machinery during unfavorable conditions. However, the molecular mechanisms stabilizing these assemblies—and their biological significance—are unknown. This project aims to resolve the structure of ribosome tetramers and identify the RNA and protein components involved in their formation.
To achieve this, the project will combine cryo-electron tomography (cryo-ET), XFEL crystallography, and SHAPE probing. Cryo-ET will be used to determine the three-dimensional structure of ribosome tetramers both in vitro and in situ. XFEL crystallography may allow structure determination of ordered tetramers at near-atomic resolution. SHAPE (Selective 2’-Hydroxyl Acylation analyzed by Primer Extension) will provide complementary information on rRNA flexibility and inter-ribosomal contacts. Additional techniques—such as 2D gel electrophoresis and mass spectrometry—will identify associated protein factors.
The project is organized into two phases: [1] high-resolution structural analysis of isolated tetramers, and [2] cellular tomography to observe ribosome aggregation in their native environment. Advanced instrumentation and data processing, including deep learning-based software for particle detection, will be employed to maximize structural insight.
The expected outcome is a comprehensive structural and molecular model of ribosome hibernation in a chick embryo. Understanding how ribosome tetramers form and function could reveal fundamental aspects of translation regulation during stress and development. Moreover, these findings may have broader applications in regenerative medicine, stem cell therapy, and organ preservation, where energy conservation and cellular resilience are critical.
