Host Research Group
FR21_Single-molecule Biophysics group_Mikayel Aznauryan-Carmelo Di Primo
Mikayel Aznauryan / Carmelo Di Primo
+33 5 40 00 30 46
https://www.aznauryan-lab.com/
Group description
The group is working on the following main research projects:
- investigation of intrinsically disordered proteins (in particular those involved in eukaryotic translation initiation process) and their interactions with nucleic acids,
- understanding the molecular mechanisms of function of disordered RNA-binding proteins in liquid-liquid phase separation and cellular condensates,
- measuring biomolecular binding kinetics, including ternary complexes, fragile targets, strong non-specific binding, thanks to original methodological developments in SPR for instance for measuring the active concentration of anti-HLA antibodies from transplanted patients (collaboration with the CHU Bordeaux-Pellegrin), identifying molecules, aptamers, that could be used to detect viruses.
Keywords
- Intrinsically disordered proteins
- Single-molecule FRET
- Liquid-Liquid Phase Separation
- Molecular interactions
- Nucleic acids
- Molecular biophysics
- Surface Plasmon Resonance
- Isothermal Titration Calorimetry
- NMR
- Fluorescence and UV-Visible spectroscopy
Team Description
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Mikayel Aznauryan (Principle Investigator)
ORCID: 0000-0002-5395-3441
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Carmelo Di Primo (Research staff)
ORCID: 0000-0002-0509-8399
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Sabrina Rousseau (Research staff)
ORCID: -
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Bikash Chandra Swain (Post-Doctoral Researcher)
ORCID: -
Projects
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BioMint Incubator LTC Sarea
Pl: Carmelo Di Primo
Funding Agency*: International
Ongoing: yes
Project reference: -
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FUnctional Nucleic Acids as Versatile SMart BUilding BLocks in Non-ConventIonal SolvenTs
Pl: Carmelo Di Primo
Funding Agency*: EU
Ongoing: yes
Project reference: -
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DISTINCT: Exploring the molecular mechanisms of the function of disordered proteins at the initiation of translation: from in vitro to the cell
Pl: Mikayel Aznauryan
Funding Agency*: National
Ongoing: yes
Project reference: -
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4B4CANCER
Pl: Mikayel Aznauryan
Funding Agency*: Regional
Ongoing: yes
Project reference: -
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IDPRNA
Pl: Mikayel Aznauryan
Funding Agency*: EU
Ongoing: no
Project reference: -
Publications
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Li G, Ko CN, Li D, Yang C, Wang W, Yang GJ, Di Primo C, Wong VKW, Xiang Y, Lin L, Ma DL, Leung CH., = A small molecule HIF-1α stabilizer that accelerates diabetic wound healing., Nat Commun., 2021
10.1038/s41467-021-23448-7. -
Di Primo C., = Surface Plasmon Resonance for Investigating Molecular Interactions with RNA, Methods Mol Biol, 2020
10.1007/978-1-0716-0278-2_6 -
Dausse E, Barré A, Aimé A, Groppi A, Rico A, Ainali C, Salgado G, Palau W, Daguerre E, Nikolski M, Toulmé JJ, Di Primo C, = Aptamer selection by direct microfluidic recovery and surface plasmon resonance evaluation, Biosens Bioelectron, 2016
10.1016/j.bios.2016.02.003 -
Aznauryan M., Noer S.L., Pedersen W.P., Mergny J-L, Teulade-Fichou M-P, Birkedal V., = Ligand binding to dynamically populated G‐quadruplex DNA, ChemBioChem, 2021
10.1002/cbic.202000792 -
Aznauryan M., Delgado L., Soranno A., Nettels D., Huang J-R, Labhardt A.M., Grzesiek S., Schuler B. Comprehensive structural and dynamical view of an unfolded protein from the combination of single-molecule FRET, NMR, and SAXS PNAS 2016 doi: 10.1073/pnas.1607193113, = Aznauryan M., Delgado L., Soranno A., Nettels D., Huang J-R, Labhardt A.M., Grzesiek S., Schuler B. Comprehensive structural and dynamical view of an unfolded protein from the combination of single-molecule FRET, NMR, and SAXS PNAS 2016 doi: 10.1073/pnas.1607193113, Proceedings of the National Academy of Sciences, 2016
10.1073/pnas.1607193113
Research Lines
ADVANCED MATERIALS AND PROCESSES
Molecular sensors for detection
Surface plasmon resonance (SPR) is a gold standard technique for analyzing molecular interactions. Only sensitive to mass changes it allows measuring binding parameters (affinity, kinetics, specificity) which are helpful not to say mandatory to better understand function in relation to the structure of the molecules. In recent years C Di Primo has been involved in the use of SPR for clinical applications in collaboration with the CHU Bordeaux Pellegrin (J. Visentin and JL Taupin). This work, aimed at detecting anti-HLA antibodies from transplanted patients, has been supported for clininal application by the SATT Aquitaine. A new method has been developed, patented, which also lead to publications. C. Di Primo has shown that SPR can be used to detect microRNAs (nucleic acid biomarkers) down to 10 pM. T. Schäfer as a chemical engineer is developing surfaces for detection and separation. Our complementary expertise and our common interest in nucleic acids and molecular interactions has triggered a colloboration that is focused on how to use hybrid materials for sensing biomarkers or emerging contamintants.
INTELLIGENT, FLEXIBLE & EFFICIENT PRODUCTION SYSTEMS
Functional Nucleic Acids as Versatile Smart Building Blocks in Non-Conventional Solvents
The objective of this research line is to create a modular, cross-cutting toolbox for custom fine chemistry that will exploit nucleic acids' chirality, chemical reactivities and molecular recognition properties in non-conventional solvents (ionic liquids and deep eutectic solvents). The approach should open new avenues for the identification of molecules of therapeutic interest in addition to better understanding how nucleic acids behave in such media. Again both expertises, in San Sebastian and in Bordeaux, will be shared in this project together with other European partners.
Carmelo Di Primo (IECB/Univ Bordeaux, Pessac ) and Thomas Schäfer (POLYMAT, Univ Pais Vasco, San Sebastian) have been collaborating in the field of DNA-nanotechnology and characterization of biomolecular interaction phenomena since 2013. Triggered by the COVID-19 pandemic, the collaboration intensified from 2020 on with a project, SARSense, in the frame of the Resilience Covid programme funded by Euskampus, with the goal of identifying nucleic acids (aptamers) which would be able to prevent the entry of the virus within the cells and/or to detect it. This work is still ongoing. After several years sharing expertise with technologies dedicated to analyze molecular interactions for understanding function and developing molecular sensors, we thought of creating a technological cross-border platform between the University of Bordeaux and the Universidad del Pais Vasco to be opened to academic laboratories and private companies in our regions. Understanding molecular interactions through the determination of binding parameters (affinity, kinetic and specificity) is a mandatory step to link biological functions to the three-dimensional structure of the molecules but also to develop molecular probes for detection. In 2022 a cross border laboratory (LTC Incubator) , "Biomolecular Interactions platform: BioMint" has been approved and funded by Euskampus to share these expertises with our communities. One of the instruments of the future platform, which will be purchased next year, is co-funded by the Région Nouvelle Aquitaine, Univ. of Bordeaux (Fédération des plateformes), the DIPC (San Sebastian), 3 private companies (2 in Gironde, one in San Sebastian) and academic laboratories in Bordeaux. We both hope that this is a first step towards a cross-border laboratory with a special focus on molecular interactions. More recently and under the coordination of Thomas Schäfer, C Di Primo is one of the eight partners of an EIC Pathfinder project "FUnctional Nucleic Acids as Versatile SMart BUilding BLocks in Non-ConventIal SolvenTs (FUNAMBULIST) that is now funded by the EU and will start in 2023.