ERC SUMMIT – Site-specific Ultrasensitive Magnetic resonance of Mixtures for Isotopic Tracking

Exploring the potential of fast and hyperpolarized nuclear magnetic resonance methods for “omics” sciences, this project is led by Patrick Giraudeau and the MIMM research team relies on cutting-edge equipments from the CEISAM NMR platform.

6-year project

2019 - 2025

€ 1 999 768

ERC funds

211

person-months effort over the 5 years

7

internal team members

summit erc logo ceisam.png

The SUMMIT team is developing new tools based on nuclear magnetic resonance (NMR) to obtain information on complex biological questions in the areas of life, environmental, food and forensic sciences.

NMR is a cutting-edge technique that provides crucial information on molecules in biological samples at the atomic level. For instance, NMR can help finding new biomarkers of a certain pathology, or provide information on the authenticity of a food sample. In this context, SUMMIT is developing more sensitive and resolutive methods, that will be applied to a variety of biological questions.

 

In more details

Metabolomics, fluxomics and isotopomics show great promises towards tracking the origin of biomarkers in complex biological environments, in the areas of life, environmental, food and forensic sciences. NMR spectroscopy is a major cutting-edge analytical tool for such “omics” sciences thanks to its high quantitative and structure elucidation potential, and to its ability to access site-specific isotope content. 13C NMR plays a central role, but numerous applications are currently out of reach of 13C NMR due to its low sensitivity.

The SUMMIT team is developing a groundbreaking analytical workflow relying on two of the most powerful NMR methods: dissolution dynamic nuclear polarization and ultrafast 2D NMR. This approach will allow the simultaneous measurement of 13C fingerprints from multiple low-concentrated biomarkers molecules in complex mixtures, which is impossible with existing methods. The high potential of this analytical strategy will be demonstrated on a variety of relevant biological studies, through applications in metabolomics, fluxomics and isotopomics.

Project team

Patrick GIRAUDEAU

Professor at the University of Nantes

Project leader

Marine LETERTRE

Associate professor

NMR metabolomics

Jean-Nicolas DUMEZ

CNRS research associate

NMR pulse sequence developments

Victor RIBAY

PhD student
Development in d-DNP and metabolomics
(2021-2024)

Benoît CHARRIER

Engineer

d-DNP instrumentation

Sumit MISHRA

Post-doctoral researcher

(2024-2025)

Past members

Stéphanie TESSIER

Project Manager

Finances, human ressources, management and reporting

Marine PIOU

Engineer
Signal processing
(2021-2022)

Arnab DEY

Post-doctoral research associate
d-DNP developments
(2019-2022)

Clément PRAUD

PhD student
NMR pulse sequence developments
(2020-2023)

Célia LHOSTE

PhD Student
NMR pulse sequence developments
(2020-2023)

Publications

22. Exploring the complementarity of fast multipulse and multidimensional NMR methods for metabolomics: a chemical ecology case study (link)
Auteurs :  A. Michaud, S. Bertrand, S. Akoka, J. Farjon, E. Martineau, N. Ruiz, T. Robiou du Pont, O. Grovel, P. Giraudeau

21. Autonomous reaction self-optimization using in-line high-field NMR spectroscopy (link)
Auteurs : N. El Sabbagh, M. Bazzoni, Y. Horbenko, D. Cortes-Borda, A. Bernard, P. Giraudeau, F.-X. Felpin and J.-N. Dumez

This work shows how in-line detection by high-field NMR combined with a feedback look can be used to drive the autonomous self optimisation of reaction conditions.

20. Non-uniform sampling to enhance the performance of compact NMR for characterizing new psychoactive substances (http://dx.doi.org/10.1002/mrc.5416)
Authors: Thomas Castaing-Cordier, Sélina Crasnier, Damien Dubois, Virginie Ladroue, Audrey Buleté, Cédric Prudhomme, Céline Charvoz, Fabrice Besacier, Denis Jacquemin, Patrick Giraudeau, Jonathan Farjon

19. Optimization of heteronuclear ultrafast 2D NMR for the study of complex mixtures hyperpolarized by dynamic nuclear polarization (link)
Authors: Clément Praud, Victor Ribay, Arnab Dey, Benoît Charrier, Joris Mandral, Jonathan Farjon, Jean-Nicolas Dumez, and Patrick Giraudeau

This work provides a rigorous characterisation of the sensitivity and repeatability of the combination of dissolution dynamic nuclear polarisation and ultrafast 2D NMR, which are important for analytical applications.

18. Hyperpolarized 1H and 13C NMR Spectroscopy in a Single Experiment for Metabolomics (link)
Authors: Arnab Dey, Benoît Charrier, Victor Ribay, Jean-Nicolas Dumez and Patrick Giraudeau

This work shows that hyperpolarised 13C and 1H 1D NMR spectra can be acquired in a single dissolution dynamic nuclear polarisation experiment, with signal enhancements of several orders of magnitude.

17. Solution-state 2D NMR spectroscopy of mixtures hyperpolarized using optically polarized crystals (link)
Authors: Anna J. Parker, Arnab Dey, Mohammed Usman Qureshi, Jakob M. Steiner, John W. Blanchard, Jochen Scheuer, Nikolas Tomek, Stefan Knecht, Felix Josten, Christoph Muller, Patrick Hautle, Ilai Schwartz, Patrick Giraudeau, Tim Eichhorn, Jean-Nicolas Dumez

16. Broadband ultrafast 2D NMR spectroscopy for online monitoring in continuous flow (link)
Authors: Célia Lhoste, Margherita Bazzoni, Justine Bonnet, Aurélie Bernard, François-Xavier Felpin, Patrick Giraudeau, Jean-Nicolas Dumez

15. Scaling-up metabolomics: Current state and perspectives (link)
Authors: Ghina Hajjar, Millena C. Barros Santos, Justine Bertrand-Michel, Cécile Canlet, Florence Castelli, Nicolas Creusot, Sylvain Dechaumet, Binta Diémé, Franck Giacomoni, Patrick Giraudeau,Yann Guitton, Etienne Thévenot, Marie Tremblay-Franco, Christophe Junot, Fabien Jourdan, François Fenaille, Blandine Comte, Pierre Pétriacq, Estelle Pujos-Guillot

14.  NMR metabolite quantification of a synthetic urine sample: an inter-laboratory comparison of processing workflows (link)
Authors: Cécile Canlet, Catherine Deborde, Edern Cahoreau, Grégory Da Costa, Roselyne Gautier, Daniel Jacob, Cyril Jousse, Mélia Lacaze, Inès Le Mao,
Estelle Martineau, Lindsay Peyriga, Tristan Richard, Virginie Silvestre, Mounir Traïkia, Annick Moing, Patrick Giraudeau 

13. Book chapter: Fast 2D NMR for metabolomics (link)
Authors: Clément Praud, Marine P.M. Letertre, Arnab Dey, Jean-Nicolas Dumez, Patrick Giraudeau

12. Book chapter: Fast 2D NMR for reaction and process monitoring (link)
Authors: Margherita Bazzoni, Benjamin Lorandel, Célia Lhoste, Patrick Giraudeau, Jean-Nicolas Dumez

11. Hyperpolarized 13C NMR Spectroscopy of Urine Samples at Natural Abundance by Quantitative Dissolution Dynamic Nuclear Polarization (link)
Authors: Victor Ribay, Arnab Dey, Benoît Charrier, Clément Praud, Joris Mandral, Jean-Nicolas Dumez, Marine P.M. Letertre, and Patrick Giraudeau

10. Quantitative NMR spectroscopy of complex mixtures (link)
Author: Patrick Giraudeau

9. Hyperpolarized NMR metabolomics (link)
Authors: Victor Ribay, Clément Praud, Marine P. M. Letertre, Jean-Nicolas Dumez and Patrick Giraudeau

8. In-line Multidimensional NMR Monitoring of Photochemical Flow Reactions (link)
Authors: Margherita Bazzoni, Célia Lhoste, Justine Bonnet, Kouakou Eric Konan, Aurélie Bernard, Patrick Giraudeau, François-Xavier Felpin and Jean-Nicolas Dumez

This work demonstrates the in-line monitoring of a flow photochemical reaction using 1D and ultrafast 2D NMR methods at high magnetic field.

7. Fine optimization of a dissolution dynamic nuclear polarization experimental setting for 13C NMR of metabolic samples (link)
Authors: Arnab Dey, Benoît Charrier, Karine Lemaitre, Victor Ribay, Dmitry Eshchenko, Marc Schnell, Roberto Melzi, Quentin Stern,
Samuel F. Cousin, James G. Kempf, Sami Jannin, Jean-Nicolas Dumez, and Patrick Giraudeau

6. Ultrafast 2D NMR for the analysis of complex mixtures (link)
Authors: Célia Lhoste, Benjamin Lorandel, Clément Praud, Achille Marchand, Rituraj Mishra, Arnab Dey, Aurélie Bernard, Jean-Nicolas Dumez, Patrick Giraudeau

This review article describes ultrafast 2D NMR and its applications in the fields of monitoring, metabolomics, hyperpolarization and oriented media.

5. Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives (link)
Authors: Marine P. M. Letertre, Patrick Giraudeau and Pascal de Tullio

4. Ultrafast 2D 1H-1H NMR spectroscopy of DNP-hyperpolarised substrates for the analysis of mixtures (link)
Authors: Kawarpal Singh, Corentin Jacquemmoz, Patrick Giraudeau, Lucio Frydman, Jean-Nicolas Dumez

3. Combined Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry Approaches for Metabolomics (link)
Authors: Marine P. M. Letertre, Gaud Dervilly, and Patrick Giraudeau

Graphical abstract

2. Hyperpolarized NMR Metabolomics at Natural 13C Abundance (link)
Authors: Arnab Dey, Benoît Charrier, Estelle Martineau, Catherine Deborde, Elodie Gandriau, Annick Moing, Daniel Jacob, Dmitry Eshchenko, Marc Schnell,
Roberto Melzi, Dennis Kurzbach, Morgan Ceillier, Quentin Chappuis, Samuel F. Cousin, James G. Kempf, Sami Jannin, Jean-Nicolas Dumez, and Patrick Giraudeau

TOC_030620

1. NMR-based metabolomics and fluxomics: developments and future prospects (link)
Author: Patrick GIRAUDEAU

NMR-based metabolomics and fluxomics developments and future prospects