Aznauryan Team Molecular biophysics of disordered proteins

Single-molecule spectroscopy of disordered protein dynamics and interactions

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Aznauryan Team Molecular biophysics of disordered proteins

We are interested in molecular understanding of the behavior of intrinsically disordered proteins (IDPs) and the mechanisms of their interactions with nucleic acids and proteins.

For this purpose we use a large bouquet of state-of-the-art techniques, among which the central role is attributed to single-molecule spectroscopy in combination with Förster resonance energy transfer (single-molecule FRET), both in vitro and in live cells.

 

Selected publications:

Swain B.C., Sarkis P., Ung V., Rousseau S., Fernandez L., Meltonyan A., Aho V.E., Mercadante D., Mackereth C.D. & Aznauryan M. Disordered regions of human eIF4B orchestrate a dynamic self-association landscape, Nature Communications 15, 8766 (2024)

Mondal S, Rousseau S, Talenton V, Thiam CAB, Aznauryan M, Mackereth CD, Backbone resonance assignments of the C-terminal region of human translation initiation factor eIF4B, Biomol NMR Assign. 17, 199–203 (2023)

Aznauryan M. and Birkedal V. Dynamics of G-Quadruplex Formation under Molecular Crowding, J. Phys. Chem. Lett. 14, 10354–10360 (2023)

Team Leader

  • AZNAURYAN Mikayel
  • INSERM researcher
  • 0540002537
  • %6d%2e%61%7a%6e%61%75%72%79%61%6e%40%69%65%63%62%2e%75%2d%62%6f%72%64%65%61%75%78%2e%66%72
AZNAURYAN Mikayel

Mikayel Aznauryan earned his PhD from Yerevan State University in Armenia (2008-2011). He then moved to Switzerland (2012-2014) as a postdoctoral researcher in the Department of Biochemistry at the University of Zurich (under Prof. B. Schuler), where he focused on protein folding and dynamics using single-molecule FRET spectroscopy. Following this, he continued his postdoctoral research (2014-2018) at the Department of Chemistry and the Interdisciplinary Nanoscience Center at Aarhus University in Denmark (under Prof. V. Birkedal), where he employed single-molecule fluorescence microscopy to study the dynamics of nucleic acid structures.

In late 2018, Mikayel Aznauryan joined IECB and the ARNA Laboratory as a new group leader. Since 2019, he has been an INSERM senior researcher (CRCN). He has been awarded FRM start-up, IdEx Chair of Excellence, and ANR Young Investigator grants to establish his group.

Intrinsically disordered proteins (IDPs) or proteins containing intrinsically disordered regions (IDRs) are ubiquitous in eukaryotic proteome. They are largely involved in various biological processes that ensure normal cellular physiology and are also implicated in various pathologies, including cancers and neurodegenerative diseases. These proteins typically lack persistent structure in their native form and do not necessarily require defined structure for molecular recognition and specific function. They are frequently involved in phase separation-driven assembly of various cellular condensates. 

The key expertise of the group is centered on in vitro and in-cell single-molecule FRET spectroscopy, which is our main tool to probe disordered proteins and their interactions. For this purpose, we also use a variety of other state-of-the-art biochemical and biophysical techniques, such as biomolecular nuclear magnetic resonance (NMR) spectroscopy, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), live-cell imaging and molecular simulations, to obtain a comprehensive picture of disordered protein behavior and mechanisms of their interactions with nucleic acids and other proteins, with a goal of revealing the basis of their specific function.

Currently, the main axes of our research are focused on the following topics:

- investigation of the behavior and interactions of disordered translation initiation factors and uncovering the mechanistic principles of their function in eukaryotic translation;

- investigation of the self-association properties of disordered translation initiation factors and molecular mechanisms of their condensation, with a goal of understanding their function in cellular stress response and assembly biomolecular condensates.

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