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

The metabolome refers to the set of small organic compounds (metabolites) present in a biological environment. The objective of metabolomic analysis in biomedical research is to characterize biomarkers by comparing metabolic fingerprints containing several thousand signals using appropriate statistical analysis tools. This type of approach opens promising perspectives, covering for example the areas of nutrition, pathology or toxicity marking, and at a more fundamental level the global understanding of living systems.
Based on various analytical techniques based on high resolution mass spectrometry, our laboratory develops tools to explore metabolome, but also lipids (lipidomics) and free glycans linked to lipids and proteins (glycomic) . These last two classes of biomolecules are closely related to each other and to metabolism and we exploit the versatility of mass spectrometry to achieve the most exhaustive detection possible of all these molecular species in order to enhance our chances of characterizing biomarkers. Our laboratory is involved in the constitution of spectral databases of metabolites and lipids. We also develop methods for the absolute quantification of metabolites in biological fluids.
The main applications concern biomedical research in the fields of neurology, microbiology, hematology, diabetology, cancerology and allergology in collaboration with medical teams, biologists and pharmaceutical manufacturers and diagnosis. This metabolomic analysis activity received an IBiSA (Metabolome IDF) label in 2010 and resulted in the creation of Profilomics in July 2010. The laboratory is involved in the construction of a national metabolomic infrastructure funded by investments for the future(National INfrastructures in Biology and Health, project MetaboHUB). Lastly, a collaboration with the company medDay pharmaceuticals was initiated in 2014 for the research of biomarkers of neurological diseases. 

Mass spectrometry applied to therapeutic, biomarker or bioterroristic proteins (NRBC program)

Through its technology and know-how, our laboratory tries to meet the challenges of the pharmaceutical industry in the coming years. Firstly of all, the advent of products derived from so-called recombinant technologies has led to the development of new therapeutic concepts: recombinant proteins (eg humanized antibodies), siRNAs or antisense oligonucleotides. These developments involve original structural characterization and quantification techniques that we propose to the pharmaceutical and agro-food industry. As part of this activity, more than a dozen industrial collaborations have already been initiated since 2005.
Another application concerns the diagnostic activity in the field of biomarkers. To date, the reference techniques are ELISA-type enzyme immunoassays. However, these techniques may sometimes lack specificity and / or reproducibility and our objective is to propose alternative approaches based on the combination immunoaffinity and mass spectrometry. This  research topic makes collaborations with teams of clinicians and hospital biologists possible.
Finally, these analytical developments are exploited in favor of the detection of proteins related to bioterrorism activities. As part of the CEA's Nuclear Radiological Biological (CBRN) program, our laboratory develops tools for the detection of toxins and bacteria that are considered potential threats. A combined approach of immunoextraction and targeted mass spectrometry yielded particularly sensitive methods for agents such as ricin (detection of 100 μg / ml ricin) or Bacillus anthracis spores (detection of 7.103 spores / mL).

Mass spectrometry applied to pharmacokinetics and drug metabolism

We develop, validate and use methods for detecting, quantifying and identifying drug candidates and their metabolites in different biological fluids and tissues by liquid chromatography coupled with mass spectrometry (low and high resolution) for partners in the academic and industrial sectors . The laboratory has acquired recognized expertise in the field of pharmacokinetics and the metabolism of anti-HIV drugs.
We are involved in various projects funded by the ANR, ANRS, the European Union or pharmaceutical companies on problems of monitoring efficiency, simplification and / or modification of treatments, and also in the exploration of new forms of therapies and the search for drug candidates for rare or neglected diseases.

Alain Pruvost is also responsible for the platform SMArt-MS​ within the SPI.