The research project of our group is translational with the aim to find new biomarkers of left ventricular remodeling post-infarction and heart failure. The team has expertise on coordinating recruitment of patients with cardiac disorders, clearly phenotyped for left ventricular remodeling post-infarction (REVE 1 (n=266) and REVE 2 (n=246) studies) or heart failure (PTHF (n=60) and INCA (n>2000) studies. These clinical studies allow recuperating plasma and serum samples that are used for differential proteomic and transcriptomic (miRNA and lncRNA) analyses. We have developed techniques allowing access and detection of plasma “deep” proteome. We have the expertise in discovery and validation of targets from proteomic (SELDI-TOF, 2D-DIGE, multiplex, ELISA) and miRNAomic (arrays, Q-RT-PCR).

Two approaches are currently developed: 1) a clinical approach with the purpose to develop clinical diagnostic applications for which we analyzed all the data obtained by system biology and; 2)  a molecular approach with the purpose to understand the mechanisms underlying the targets (proteins, post-translational modified proteins, miRNA, lncRNA ) modulation in the pathologies studied. The discovery of new biological factors involved in the different cardiovascular pathologies would help to a better stratification of patients at risk.

Notre unité de recherche étudie les toxines bactériennes protéiques. Ces toxines produites par les bactéries pathogènes sont largement responsables des aspects physiopathologiques qui surviennent lors de la phase aiguë de l’infection. Il est essentiel de définir le mode d’action des toxines et leur fonction pour prédire le potentiel pathogène de souches bactériennes isolées chez le malade ou dans l’environnement ainsi que d’adopter des stratégies de traitement thérapeutique adaptées. L’étude de ces protéines remarquablement puissantes est aussi moteur dans la compréhension des processus biologiques fondamentaux et nous permet d’envisager leur utilisation comme agent thérapeutique. C’est par exemple le cas des neurotoxines de clostridium, un des groupes de toxines étudiées au laboratoire, et qui sont utilisées pour bloquer la transmission nerveuse cholinergique et ainsi bloquer les contractions musculaires involontaires.

Nos études sont centrées sur l’étude du mode d’action des toxines bactériennes en lien avec leur impact sur la fonction de barrière des épithélium et endothélium. Nous déterminons les mécanismes moléculaires intimes qui permettent aux toxines de briser ou franchir ces barrières pour favoriser la dissémination des bactéries et des toxines dans l’organisme, ainsi que les mécanismes autonomes cellulaires de limitation des effets cytotoxiques. Nos modèles d’études comprennent les toxines bactériennes qui ciblent le cytosquelette d’actine et ses régulateurs amont, que nous étudions par des approches multidisciplinaires de Biologie Cellulaire, Biochimie et Physique. Nous étudions un nouveau mode de perturbation de la barrière endothéliale par « démouillage cellulaire » qu’induit la perturbation de la contractilité du cytosquelette d’actomyosine. Nous étudions aussi la régulation des GTPases Rho par dégradation protéasomale médiée par l’ubiquitine et son importance dans l’invasion des tissus et cellules par les bactéries pathogènes. Nos études nous ont permis de développer de nouvelles approches de diagnostic et thérapeutiques en particulier pour les neurotoxines, et de nouvelles stratégies adjuvantes en vaccinologie. L’étude des toxines bactériennes et de leur cibles cellulaires nous renseigne plus généralement sur les processus infectieux mais aussi sur des mécanismes moléculaires dérégulés dans un grand nombre de maladies humaines telles que les maladies inflammatoires et le cancer.

The lab is studying the role and the functioning of the trypanosome flagellum, with perspectives in the field of both parasitology and genetic diseases.

Indeed, trypanosomes are significant parasites of man and cattle in central Africa and there are currently no efficient vaccines against them. Moreover, trypanosomes are also an excellent model to study human genetic diseases due to defects in cilia and flagella.

The lab is a Pasteur full research unit and is affiliated to the Department of Parasites and Insect Vectors (headed by Ken Vernick) but also to the Department of Cell Biology and Infection (headed by Chiara Zurzolo). We also belong to a larger INSERM unit (U1201, headed by Artur Scherf) that involves two other teams working on Plasmodium and on Leishmania. We are also part of the LabEx IBEID, a consortium coordinated by Professors Philippe Sansonetti and Pascale Cossart whose aim is to develop a structure to anticipate and tackle emerging infectious diseases (EIDs).

Finally, the lab is labelled as “équipe FRM” (Fondation pour la Recherche Médicale)

Eukaryotic cells contain extensive internal membranes defining many compartments having each specific functions. However these organelles are constantly moving and reshaping, still retaining their identity. The maintenance of cell compartmentalization in eukaryotes is thus very complex and tightly controlled. Nathalie Sauvonnet’s team deals with intracellular trafficking of eukaryotic cells and how it regulates cell and tissue organization. In particular we study endocytosis and exocytosis pathways and their linked to lipid distribution, cell compartmentalization and host-pathogen interactions. For this purpose we used an array of techniques from high resolution microscopy, single molecules tracking, robust image analysis, statistical classification, crispR-cas9 edition to organ-on-a-chip.

Our research focuses on the control of cell migration in health and disease. Cell migration is essential during development as well as in adult as it contributes to immune responses, tissue renewal, wound healing. In addition, cell migration and invasion is characteristic of highly malignant tumours that spread into the surrounding tissue to eventually metastasize 21,22. Migrating isolated cells but also migrating groups, sheets or chains of cells have been observed during physiological and pathological situations. Initiation of migration first requires cell polarization along a front to rear axis. Extracellular cues guiding polarization and migration include soluble factors such as chemoattractants and repellant as well as biochemical and biophysical properties of the extracellular matrix and of surrounding cells.  These extracellular signals are transduced in intracellular signaling pathways that involve evolutionary conserved polarity proteins. The process of migration relies on the coordinated regulation of different cytoskeletal elements including actin, microtubule and intermediate filaments. This regulation occurs downstream of the polarity proteins to insure that the cytoskeletal networks organized in a polarized manner.