The mass spectrometry team’s main research theme is the gas-phase structural chemistry of natural compounds, with a three-fold perspective: fundamental aspects, methodology and applications. The aim is to offer new tools in analytical chemistry and bioinformatics, in close interaction with academic and industrial specialists in biology, medicine and the environment, for a better understanding of living organisms and fundamental MS processes.
Resources deployed :
- MALDI-TOF/TOF UltrafleXtreme (Bruker Daltonics)
- Liquid chromatographic system 1260Prime (LC) – Q-ToF 6540 (Agilent Technologies)
- Supercritical fluid chromatographic system 1260SFC (SFC) – Q-TOF 6546 (Agilent Technologies)
Nicolas Elie is engineer at CNRS.
Vincent Guérineau is engineer at CNRS
Salomé Poyer is a CNRS Assistant professor (CRCN). Her work focuses on method development to characterize isomeric structures of lipids by mass spectrometry. Since most structural isomeric features are accessible through C-C bond cleavages, her research interests lie in gas-phase reactivity with transition metals and alternative activation techniques to generate radical dissociations. She also develop methods using ion mobility spectrometry to resolve isomeric spatial barriers.
David Touboul is senior scientist (DR2) at CNRS since 2008. Former student of the Ecole Normale Superieur of Cachan, he obtained his Ph.D. in Chemistry at the Paris-Sud University (France) in 2006 under the supervision of Dr. Olivier Laprévote. He developed new methodologies for biological mass spectrometry imaging including MALDI-TOF and TOF-SIMS approaches. Then he moved at ETH Zurich (Switzerland) in the group of Prof. Renato Zenobi to study non-covalent complexes and gas-phase chemistry with the financial support of Novartis (Boston, USA). Back to ICSN since 2008, he first implemented new methodologies for the structural characterization of lipids, including membrane lipids or polyketides such as acetogenins in collaboration with Prof. Pierre Champy. He then moved to the structural characterization of complex natural extracts by the means of supercritical fluid extraction and chromatography (SFE and SFC) coupled to tandem mass spectrometry (MS/MS). He finally developed new software for natural substances annotation in collaboration with the group of Marc Litaudon at ICSN. Since 2019, he is the Head of the Mass Spectrometry Group at ICSN. He authored more than 110 peer reviewed publications and received special prizes (best thesis award from the French MS association in 2007, Journal of Mass Spectrometry prize in 2006, Bronze medal CNRS in 2014 and RCM Beynon prize in 2017).
- Gas-phase reactivity: Structural characterization in MS is often limited by the energy of the bonds between the different molecules to be analyzed. To improve the specificity of natural product dissociation spectra, our team is working on adduction with different metals to induce new reactivity. Gas-phase spectroscopy and ion mobility spectrometry experiments may also be needed to better understand the mechanisms involved in these new fragmentation pathways. The advantage of this alternative is that it can be implemented on other instruments, since the non-covalent interactions required to set it up can be produced at the mass spectrometer ionization source. The specific fragmentation spectra obtained after chromatographic coupling enable further annotation of the different species present in natural product extracts.
- Molecular Network: Modern MS/MS data acquisition techniques (DDA and DIA) have made it increasingly difficult to process these data in a non-automated way. In this context, our team is developing new tools based on molecular networks. The classic approach described on the historical GNPS platform has been improved by using the t-SNE (t-distributed stochastic neighbor embedding) algorithm to organize the dataset. For further information, please visit the dedicated website: https://metgem.github.io/
Thanks to its sensitivity and specificity, mass spectrometry is a particularly effective tool for identifying, detecting and quantifying chemical modifications of DNA and RNA. In this context, we have developed approaches based on oligonucleotide purification by our biological collaborators, followed by MALDI-TOF/TOF mass spectrometry analysis. This enables us to measure the exact mass of modified and unmodified oligonucleotides, and to determine the position of these modifications after partial enzymatic digestion. Studies of RNA methylation kinetics have been undertaken, providing a better understanding of the processes involved in regulating these modifications. Finally, we have set up a workflow for the absolute quantification of canonical or modified nucleosides from RNA or DNA extracts.