Proteomics and structural MS represent complementary and powerful approaches for the understanding of complex biological systems. MS is a key technology in proteomic strategies offering various platforms with specific capabilities continuously improving in terms of sensitivity, mass resolution and acquisition speed. Major advances in proteomics and structural MS can also be attributed to the optimization of biochemical protocols and analytical methods for sample preparation before data acquisition, and to the development of sophisticated bioinformatics software for efficient data analysis. Based on our expertise in MS and proteomics, research projects are pursued to characterize several biological systems.

Role of human proteasome complexes

We are interested in understanding the structure/activity relationships of human proteasome, a large multi-catalytic complex in charge of intracellular protein degradation and a therapeutic target for some cancers. We developed integrated strategies using in-vivo crosslinking, affinity-purification and quantitative proteomics to characterize the diversity of proteasome complexes and their dynamics in various cells, physiological and pathological contexts. We also designed an MS-based quantitative method to measure the quantities of several proteasome subtypes in patient samples. We then optimized structural MS approaches to determine the structural features that govern protein-protein interactions and allosteric changes during proteasome association to its regulatory protein complexes.

Immunoproteomics

We developed efficient large-scale quantitative proteomic analyses (interactomics, phosphoproteomics) to obtain a detailed characterization of different cells from the adaptative and innate immune systems. This further permits us to get new insights into the molecular mechanisms of the inflammatory and immune responses. Major efforts have been invested to decipher, at the cellular and molecular levels, the functional mechanisms of T lymphocytes. We analysed in mouse primary T cells the signalosome of several key components of the TCR pathway using optimized interactomics and phosphoproteomics strategies.

Characterization of mycobacterial proteins

We are interested in the characterization of proteins and protein complexes that play a role in the formation of the mycomembrane and in the targeting of proteins to the plasma membrane, mycomembrane and extracellular medium. We also developed an expertise in the analysis of O-mannosylated proteins in mycobacteria to study their implication in the virulence of Mycobacterium tuberculosis.