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Séminaires Micalis

2 decembre 2015

Mélanie Hamon

Unité des interactions bactéries-cellulesDpt Biologie Cellulaire et Infection - Institut Pasteur

Upon infection, pathogens reprogram host gene expression. In eukaryotic cells, genetic reprogramming is induced by the concerted activation/repression of transcription factors and various histone modifications that control DNA accessibility in chromatin. Using Listeria monocytogenes as a model organism, we have been able to show that this intracellular pathogen induces specific changes in the levels of modified histones which correlate with a particular transcriptional response. The bacterial and host factors involved in these modifications will be discussed, and the results will be presented in the context of the field of epigenetics.
Mercredi 02 décembre 2015 - 11h
Auditorium - Bât. 442
INRA, Jouy en Josas


Cristel Archambaud

27nov 2015

Meriem El Karoui

University of Edinburgh, SynthSys, Scotland, UK

It has been shown in recent years that even genetically identical cells behave differently because many central processes involve molecules present in small numbers. The inherent randomness of chemical reactions then generates spontaneous fluctuations that can enslave all dependent processes. Double strand breaks are one of the most deleterious types of DNA damage because they lead death if not repaired. In Escherichia coli, the main repair pathway involves the multifunctional RecBCD enzyme, which salvages broken chromosomes by catalyzing the first step of homologous recombination. RecBCD is a heterotrimeric complex that is reportedly present in very low numbers in bacterial cells. This should lead to spontaneous fluctuations in RecBCD levels and non-genetic heterogeneity in the population. Qualitative studies based on population averages show that bacterial cells that do not express RecBCD are barely viable, while over-expression of the RecBCD protein leads to less efficient DNA repair. This suggests that the level of RecBCD expression needs to be tightly controlled, and raises the question of how bacterial cells cope with potentially large cell-to-cell fluctuations in this complex.  We have quantified cell-to-cell variability of RecBCD transcription using chromosomal transcriptional fusions and observed significant fluctuations that are consistent with very low levels of transcription. We developed a microfluidic device, combined with highly inclined illumination using laser excitation, which allows us to detect single molecules of GFP in vivo.  Using translational fusions of RecBCD to GFP we have shown that RecBCD is present in less than 10 molecules per cell. However, the level of fluctuations of each protein of the complex is surprisingly much lower than predicted by stochastic modeling. This suggests that a previously unknown regulatory network is controlling RecBCD expression to avoid potentially harmful fluctuations in RecBCD copy number.
Vendredi 27 novembre 2015 - 14h
Auditorium - Bât. 442
INRA, Jouy en Josas


Alexandra Gruss


Danilo Segovia

Faculté des Sciences de Biochimie et Biologie moléculaire de Montevideo,


The Orf virus is the causal agent of Contagious Echtyma, a pustular dermatitis disease of sheep and goats that occasionally affects humans. Orf disease has a relevant significance in the ovine production because of its highly contagious nature and its elevated rate of reinfections. The understanding of viral mechanisms of immune suppression is of great interest for developing new methods to control the disease.

In the genome of Orf virus, there is an open reading frame coding for a tyrosine phosphatase, with a 40% sequence homology with the VH1 phosphatase of Vaccinia virus. VH1 phosphatase is a virulent factor, crucial for the viability and replication of the viral particle, and the blocking of interferon-ɣ signaling in the host. Recently, it has been shown that the Orf virus phosphatase is also capable to modulate the ɣ-interferon pathway.

The objective of our project is to achieve the recombinant production of the Orf phosphatase and to perform a biochemical and structural characterization. Additionally, our team is developing a cell cultured based approach to study the phosphatase in a cellular environment and in the context of a viral infection.

Vendredi 20 novembre 2015 - 14h
Auditorium - Bât. 442
INRA, Jouy en Josas


Gwenaelle André-Leroux

Séminaire joint Micalis-MaIAGE


Angelika Gründling, Ph.D.

Professor in Molecular MicrobiologySection of Microbiology & MRC Centre for Molecular Bacteriology and InfectionImperial College London

Lundi 07 décembre 2015 - 10h30
Auditorium - Bât. 442
INRA, Jouy en Josas


A. Gruss



Equipe de Recherche en Epidémiologie Nutritionnelle (EREN)

Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS-UMR1153)

U1153 Inserm / U1125 Inra / Cnam / Univ Paris 13

UFR SMBH, Université Paris 13,

74 rue Marcel Cachin, 93017 Bobigny

NutriNet-santé is an observational prospective cohort study conducted on a large sample size (at least 150 000 participants included) followed up for sufficiently long period (10 years).

The primary objectives of the NutriNet-santé study are to study the relationship between food intake, nutrients, dietary behaviour and mortality as well as the incidence of chronic diseases: cancers, CVD, obesity and overweight, type II diabetes, hypertension, hyperlipidemia, metabolic syndromes as well as on ageing and the quality of life.

The secondary objectives are to:

-study the relationship between food intake, nutrients, dietary behaviour, physical activity and other pathologies (diseases such as thyroid, digestive, rhumatism,  skin problems with a significant social and economic impact); 

-study the determinants (sociologic, biologic, economic and cultural), the dietary behaviour, the nutritional status and the health status of French population;

-study the relationship between food intake, nutrients and dietary behaviour and biological and clinical markers;

-evaluate the impact of public health actions, especially in the field of nutrition (in term of perception, efficacy, knowledge).

  The huge amount of the collected information and the big sample size will enable the “NutriNet Santé” study to build a gigantic cohort data base covering the nutrition and health of the French population.

  The comprehensive protocol of the NutriNet-santé study and specific tools are available on line at

Vendredi 06 novembre 2015 - 14h
Auditorium - Bât. 442
INRA, Jouy en Josas


Catherine JUSTE


Satoshi Uematsu

1. Department of Mucosal Immunology, School of Medicine, Chiba University

2. Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo

High-dose ionizing radiation damages DNA and induces various disorders according to the radiation sensitivity of each organ. Above 5 Gy, gastrointestinal tract are severely injured due to DNA damages in crypt cells and develop lethal acute disorders called as gastrointestinal syndrome (GIS). Although the tumour suppressor p53 is a primary factor inducing death of crypt cells with DNA damage, its essential role in maintaining genome stability means inhibiting p53 to prevent GIS is not a viable strategy. Here we show that the innate immune receptor Toll-like receptor 3 (TLR3) is critical for the pathogenesis of GIS. TLR3-deficient mice show substantial resistance to GIS owing to significantly reduced radiation-induced crypt cell death. Despite showing reduced crypt cell death, p53-dependent crypt cell death is not impaired in Tlr3-deficient mice. p53-dependent crypt cell death causes leakage of cellular RNA, which induces extensive cell death via TLR3. An inhibitor of TLR3-RNA binding ameliorates GIS by reducing crypt cell death. Thus, we propose blocking TLR3 activation as a novel approach to treat GIS. In addition to acute radiation injury, cancer patients receiving abdominal irradiation frequently develop small intestinal enteropathy associated with chronic inflammation. Among the complications, fibrosis (radiation-induced intestinal fibrosis; RIF) is the most troublesome adverse effect and can result in severe bowel dysfunctions like dysmotility and obstruction. We show that RIF is mediated by interactions of intestinal eosinophils with resident myofibroblasts. Abdominal irradiation induces small intestinal fibrosis associated with excessive accumulation and degranulation of eosinophils. Following abdominal irradiation, chronic spontaneous crypt cell death causes elevation of extracellular adenosine triphosphate, which in turn activates expression of C-C motif chemokine 11 (CCL11) by resident pericryptal myofibroblasts to induce eosinophil recruitment. Eosinophil-deficient DdblGATA mice show significant attenuation of RIF. Activated myofibroblasts express granulocyte macrophage colony-stimulating factor (GM-CSF). GM-CSF induces transforming growth factor-b1 expression by eosinophils, which in turn promotes collagen expression by myofibroblasts. Upon co-stimulation with GM-CSF and CCL11, eosinophils release granule protein, which up-regulates CCL11 and profibrotic matrix metalloproteinase expression by myofibroblasts, possibly resulting in progression of eosinophil-mediated fibrogenesis. These findings provide an immunopathological mechanism for RIF and clues for developing effective therapeutic strategies.
02 novembre 2015 - 14h30
Auditorium - Bât. 442
INRA, Jouy en Josas


Nicolas Lapaque


Andrew Camilli
By developing a transposon deep sequencing approach, we were able to accurately measure the contribution of all nonessential genes of the pathogen Streptococcus pneumoniae to fitness in 22 different environments, including in the mammalian nasopharynx and lung. Among the many genes found to contribute to virulence are two (murMN) involved in determining peptidoglycan stem peptide composition. We show that their effect is mediated in part through affecting the extent of Pneumolysin (Ply) export. Ply is a cholesterol-dependent pore-forming cytolysin that is the major exported virulence factor of S. pneumoniae. Ply, which lacks a recognizable secretion motif, somehow gets exported where it initially localizes to the cell wall compartment. Using hemolysis assays we show that Ply export beyond the cell wall into the extracellular environment is inhibited by the peptidoglycan layer. By manipulating the peptidoglycan stem peptide composition, we showed that an increase in the ratio of branched to unbranched stem peptides impedes Ply release. Naturally occurring hyperactive alleles of murMN associated with penicillin resistance also impeded Ply release. Finally, we found that an increased Ply release is detrimental to virulence. These results highlight the importance of peptidoglycan composition in pathogenesis.
Vendredi 09 octobre 14h
Auditorium - Bât. 442
INRA, Jouy en Josas


Leyla Slamti


Patrick Veiga


The emergence of molecular tools brought about a revolution in the understanding of the immense diversity and functioning of the gut microbiota in health and disease. Building on these new tools and knowledge, we are dedicated to deciphering the molecular mechanisms underlying the beneficial effects of live bacteria contained in fermented milk products. As an illustration of our research effort, we recently demonstrated that host lysozyme-mediated lysis of Lactococcus lactis CNCM I-1631 facilitates the delivery of colitis-attenuating superoxide dismutase to inflamed colons.

(Ballal, Veiga, Fenn et al., 2015, PNAS)
Vendredi 11 septembre 11h
Amphithéâtre J. Poly Bât. 440
INRA, Jouy en Josas


Saulius Kaulakauskas 

01 34 65 23 82

Andrew Camilli

Rédaction : Tristan
Date de création : 02 Avril 2011
Mise à jour : 23 Novembre 2015