Project

Back to overview

NMR 600MHz for metabolomics and biomarker identification for life sciences, chemical biology and medical projects at the University of Geneva

English title NMR 600MHz for metabolomics and biomarker identification for life sciences, chemical biology and medical projects at the University of Geneva
Applicant Wolfender Jean-Luc
Number 164095
Funding scheme R'EQUIP
Research institution Laboratoire de Pharmacognosie et Phytochimie Section des Sciences Pharmaceutiques Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Pharmacology, Pharmacy
Start/End 01.01.2016 - 31.12.2016
Approved amount 809'460.00
Show all

Keywords (10)

body fluids; diabetes; mitochondrial function ; lipid quantification ; nephrology; metabolomics; metabolite profiling; biomarker identification; natural extracts; atherogenesis

Lay Summary (French)

Lead
La résonance magnétique nucléaire (RMN) est un outil indispensable pour la détermination de structures de composés organiques. L’acquisition d’un instrument à 600 MHz, muni d’une cryosonde, assurant une haute sensibilité et résolution permet l’identification de novo de métabolites ou des produits naturels obtenus en très faibles quantités. Le nouvel instrument sera dédié non seulement à l’analyse structurale mais également au profilage de matrices biologiques complexes (extraits naturels issus de plantes ou de microorganismes et fluides biologiques tels que sérum, plasma ou urine) en complément à des approches basées sur la spectrométrie de masse (MS) dans le cadre d’étude métabolomiques ayant pour but l’identification de biomarqueurs au niveau clinique et biologique.
Lay summary

Contenu et objectifs du travail de recherche

Dans le cadre de la recherche de produits naturels bioactifs, la RMN permet notamment l’identification non ambiguë de métabolites secondaires nouveaux, souvent isolés en très faibles quantités. Ceux-ci présentent un grand intérêt pour la recherche de nouveaux principes actifs au niveau préclinique, et sont parfois reconnus comme des biomarqueurs importants en écologie chimique. La RMN est également exploitée pour la caractérisation de métabolites dans les fluides biologiques d’êtres vivants. Le profilage métabolomique par RMN, fournissant des empreintes caractéristiques riches en informations, vise à l’identification de ces métabolites directement au sein des matrices analysées.

Des projets métabolomiques sur des fluides biologiques auront pour but l’identification de biomarqueurs distinctifs de pathologies données permettant ainsi de comprendre au niveau moléculaire et fonctionnel les mécanismes de réponses biologiques bien définies.

D’autres projets auront pour but d’utiliser la RMN pour la caractérisation de principes actifs nouveaux dans le cadre d’isolement ciblé à l’échelle du microgramme. Enfin, l’instrument sera mis à profit pour la quantification de lipides dans le cadre d’études lipidomiques.

Contexte scientifique et social du projet de recherche

Cet instrument sera installé dans les nouveaux laboratoires du Centre Médical Universitaire (CMU5-6) où la Section des Sciences Pharmaceutiques va déménager au printemps 2016. La localisation de cette RMN à haut champ proche d’un milieu hospitalier est une première en Suisse et permettra ainsi la réalisation de nouveaux projets notamment en recherche clinique et en bonne coordination avec les plateformes de protéomique et de spectrométrie de masse existantes à l’UNIGE.

Direct link to Lay Summary Last update: 22.01.2016

Responsible applicant and co-applicants

Publications

Publication
Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi
Brillatz Théo, Lauritano Chiara, Jacmin Maxime, Khamma Supitcha, Marcourt Laurence, Righi Davide, Romano Giovanna, Esposito Francesco, Ianora Adrianna, Queiroz Emerson F., Wolfender Jean-Luc, Crawford Alexander D. (2018), Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi, in PLOS ONE, 13(4), e0196195-e0196195.
Bioactive Natural Products Prioritization Using Massive Multi-informational Molecular Networks
Olivon Florent, Allard Pierre-Marie, Koval Alexey, Righi Davide, Genta-Jouve Gregory, Neyts Johan, Apel Cécile, Pannecouque Christophe, Nothias Louis-Félix, Cachet Xavier, Marcourt Laurence, Roussi Fanny, Katanaev Vladimir L., Touboul David, Wolfender Jean-Luc, Litaudon Marc (2017), Bioactive Natural Products Prioritization Using Massive Multi-informational Molecular Networks, in ACS Chemical Biology, 12(10), 2644-2651.
Deep metabolome annotation in natural products research: towards a virtuous cycle in metabolite identification
Allard Pierre-Marie, Genta-Jouve Grégory, Wolfender Jean-Luc (2017), Deep metabolome annotation in natural products research: towards a virtuous cycle in metabolite identification, in Current Opinion in Chemical Biology, 36, 40-49.

Collaboration

Group / person Country
Types of collaboration
University of Neuchâtel / Institute of Biology Platform of Analytical Chemistry (NPAC) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
University of Geneva / Translational Biomarker Group Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Firmenich SA Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration
University of Geneva / Pharmaceutical Analysis Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
University of Gainesville United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
6th Brazilian Conference on Natural products and XXXII RESEM Talk given at a conference Innovative metabolomics approaches for the efficient search of valuable bioactive natural products 05.11.2017 Vitoria, Brazil Wolfender Jean-Luc;
65th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA) Poster Generation of novel bioactive “unnatural” natural products through biotransformation by the enzymatic secretome of Botrytis cinerea 03.09.2017 Basel, Switzerland Wolfender Jean-Luc;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Journée Inaugurale de l'EPGL Western Switzerland 2017
Talks/events/exhibitions inauguration du CMU 5-6 UNIGE Western Switzerland 2016

Awards

Title Year
Poster award 2017 of the Society for Medicinal Plant and Natural Product Research (GA) for the poster : “Unnatural” natural products obtained by direct halogenation of crude plant extracts: the case study of Arrabidaea brachypoda Awarded to Davide Righi , phD Student Wolfender's lab 2017

Associated projects

Number Title Start Funding scheme
182438 Improving natural products chemical biodiversity for drug discovery by fungal secretome assisted biotransformation 01.04.2019 Project funding (Div. I-III)
147637 Novel avenues in mitochondrial function and diabetes 01.11.2013 Sinergia
124112 Inflammation and acute coronary syndrome (ACS) - novel strategies for prevention and clinical management 01.02.2009 SPUM
163424 Localisation and dynamics of free and bound 12-oxo-phytodienoic acid (OPDA) pools in Arabidopsis 01.07.2016 Project funding (Div. I-III)
159714 Diffusion MRI in chronic kidney patients 01.10.2015 Project funding (Div. I-III)
189921 An in silico and chemo-biological approach to identify anti-infective and pro-metabolic natural products 01.04.2020 Sinergia
171352 Age-related renal function decline: a comprehensive study using metabolomic analysis 01.05.2017 Marie Heim-Voegtlin grants
186203 Age-related renal function decline: a comprehensive study using metabolomic analysis 01.05.2019 Marie Heim-Voegtlin grants
146142 Lipid homeostasis and function 01.04.2013 Project funding (Div. I-III)
146984 Mitochondrial function and tissue specificity of glutamate pathways in metabolic homeostasis and disease 01.04.2013 Project funding (Div. I-III)
152660 Selected topics on the control of seed germination: light, temperature and dormancy 01.01.2015 Project funding (Div. I-III)
143733 Identification of novel modes of action of plant natural products targeting fungal human and phytopathogens 01.01.2013 Interdisciplinary projects
157454 Role of tubular NADPH oxidase type 4 and distal toxicity of proteinuria in chronic kidney disease progression 01.10.2015 SNSF Professorships
149807 Allelochemical arms race in peatlands: the role of polyphenols in aboveground-belowground interactions (SPHAGNOL) 01.01.2015 Project funding (Div. I-III)

Abstract

Characterisation of metabolites is a must to deepen our outstanding of fundamental processes in various fields of life sciences. De novo identification of new bioactive molecules has been and remains the focus of natural product research and this also extends toward chemical biology. With the recent progress in systems biology and metabolomics, the pace of metabolite and biomarker characterisation has exponentially increased. The unambiguous identification of low molecular weight markers however represents still a major bottleneck in the ‘omics’ sciences.In this respect Nuclear Magnetic Resonance (NMR) is the reference method for correctly assessing a metabolites structure and its 3D configuration. It is the mandatory complement to HRMS/MS when databases are lacking for straightforward spectral MS/MS matches and is often mandatory to distinguish various types of isomers. In addition NMR is also now well established for robust profiling of complex mixtures and for de novo identification of key biomarkers. Based on the tremendous advances in NMR technology and sensitivity over the last two decades, the access to a high end high field NMR system (600 MHz) at the University of Geneva is strongly needed to acquire high resolution metabolite profiles of complex biological matrices and perform characterisation of low amounts of metabolites with high throughput.Within the School of Pharmaceutical Sciences the group of Prof. Wolfender has a renowned expertise in the de novo identification of complex natural products by NMR/MS, and metabolite profiling/metabolomics. He is presently sharing this expertise with the researchers involved in Pharmaceutical Sciences and other partners of the UNIGE as well as with researchers of the Lemanic area through various collaborative projects. In particular in the School of Biology important needs exist for complete and unambiguous identification of biomarkers present in low concentrations and isolated in small quantities. Partner at the School of Chemistry and Biochemistry will also need to access the new NMR for in depth structural characterisation and for quantification in lipidomics studies. The researchers of the Faculty of Sciences involved in metabolite profiling and characterisation studies have initiated joint projects with clinicians of the University of Geneva notably in the field of NMR metabolomics which is rapidly expanding at the clinical level. Taking advantage of a move of the School of Pharmaceutical Sciences in 2016 in new high technology laboratories of the CMU, they will have a perfect environment for expanding their interaction.The opportunity to have a new NMR in this medical surrounding will offer the unique possibility in Switzerland to perform NMR metabolomics application for clinicians on site and this will strengthen existing projects in particular in the groups of Prof Maechler, Vuilleumier, Martin and their colleagues. Furthermore this will create new avenues for innovative translational medicine projects integrating the NMR metabolomics aspects in good complementarity and partnership with the strong competences in clinical proteomics of the UNIGE.The proposed NMR acquisition at the University of Geneva will thus strengthen existing lines of research within the School of Pharmaceutical Sciences in natural products research metabolomics and biofluids’ profiling. It will considerably improve and strengthen collaborations with other groups with common needs within the Lemanic area and enable new lines of research in medical sciences between the Faculty of Medicine and the Faculty of Sciences. Various projects of researchers of the UNIGE with needs in complex metabolites profiling and biomarkers identification are described in details in this grant application.
-