Team Leader
François Fenaille

francois.fenaille@cea.fr

Development of metabolomic, lipidomic and glycomic analysis methods by mass spectrometry

The metabolome is the set of organic compounds of low size (metabolites) present in a biological environment. Objective of metabolomic analyzes in biomedical research is to characterize biomarkers by comparing metabolic blots containing several thousands of signals through appropriate statistical analysis tools. This type of approach opens promising perspectives that cover such areas as nutrition, pathology or toxicity labeling, and at a more fundamental level, the comprehensive understanding of living systems.
Relying on various analytical techniques based on high-resolution mass spectrometry, our laboratory develops metabolome exploration tools, but also lipids (lipidomic) and glycans, free or bound to lipids and proteins (glycomic). These latter two classes of biomolecules are closely linked between themselves and to the metabolism, and we use the versatility of mass spectrometry to achieve the most complete possible detection of these molecular species to enhance our chances to characterize biomarkers. Our laboratory is involved in the formation of spectral databases of metabolites and lipids. We have also developed methods of absolute quantification of metabolites in biological fluids.
The main applications relate to biomedical research in the fields of neurology, microbiology, hematology, diabetology, oncology and allergy in collaboration with medical teams, biologists and pharmaceutical and diagnostics companies. This metabolomic analysis activity obtained a IBiSA label (platform Metabolome IDF) in 2010 and has resulted in the creation of the Profilomics company in July 2010. The laboratory is also involved in building of a national infrastructure for metabolomics funded by future investments (National Infrastructures in Biology-Health project MetaboHUB).Finally, collaboration with the MEDday pharmaceuticals company was initiated in 2014 for the research of neurological disease biomarkers.

Mass spectrometry applied to therapeutic proteins, biomarkers or bioterrorism proteins (CEA CBRN-E program)

Through its technology and know-how, the lab is trying to meet the challenges of the pharmaceutical industry in the coming years. First, the advent of so-called recombinant technologies products has led to the development of new therapeutic concepts: recombinant proteins (eg. humanized antibodies), siRNA or antisense oligonucleotides. These developments involve original techniques of structural characterization and quantification that we offer to the pharmaceutical and food industries. As part of this activity, more than a dozen industrial collaborations have been initiated since 2005.
Another application relates in diagnostic activity in the field of biomarkers. To date, references techniques are enzyme immunoassays, ELISA-typed techniques. However, these techniques can sometimes lack specificity and/or reproducibility, and our goal is to offer alternative approaches based on coupling immunoaffinity with mass spectrometry. This research is the subject of collaborations with teams of clinicians and hospital biologists.
Finally, these analytical developments are operated for the benefit of the detection of proteins related to bioterrorism activities. As part of the CBRN program (Chemical Biological Radiological and Nuclear threats) carried by the CEA, our laboratory develops tools for the detection of toxins and bacteria considered as potential threats. A combined approach of immunoextraction and targeted mass spectrometry yielded particularly sensitive methods for detection of agents such as ricin (detection of 100 pg/mL of ricin) or of Bacillus anthracis spores (detection of 7.103 spores/mL).

Mass spectrometry applied to pharmacokinetics and drug metabolism

We develop, validate and use methods to detect, quantify and identify drug candidates and their metabolites in different biological fluids and tissues by liquid chromatography-mass spectrometry (low and high resolution) for partners in the academic and industrial sectors. The laboratory has developed a particular expertise in the field of pharmacokinetics and metabolism of anti-HIV drugs.
We are involved in various projects funded by the ANR, ANRS, the European Union or pharmaceutical industry on issues of monitoring efficiency, simplification and/or treatment modifications, as well as part of exploring new forms of therapy and research of drug candidates directed against rare or neglected diseases.