Abstract:
The evolutionary conserved Pif1 helicase is involved in the maintenance of both nuclear and mitochodrial genomes. Our molecular and chemical studies of the instability of the human G-rich CEB1 minisatellite in S. cerevisiae cells suggest that Pif1 play a role in the metabolism of G-quadruplex forming sequences. G-quadruplexes are nucleic acid secondary structures for which many biological roles have been proposed, but whose existence in vivo remained elusive.

Most common forms of short-term synaptic plasticities are associated with non-linear responses to calcium increases in the post-synaptic compartment. Cooperativity, a form of ultra-sensitivity where the effect of a signal increases in a non-linear fashion with the intensity of the signal, is often considered as a mean to implement a thresholding function, resulting in a molecular on-off switch. The "cooperative" nature is due to the existence of several non-independent sites responding to the signal. Those sites are often carried by different identical monomers within a symmetrical assembly, and for half a century the emerging cooperative properties have been successfully explained by the concerted model of Monod, Wyman and Changeux. Calmodulin, one of the main calcium sensors in eukaryotic cells, is a small protein that carries four calcium binding sites with different affinities. One can extend the MWC framework to explain the properties of calmodulin, and in particular the apparent increasing calcium affinity with fractional occupancy, the activity of non-saturated forms of calmodulin, and the increase in calcium affinity once calmodulin is bound to a target. Because calmodulin can bind several targets with different affinities, the allosteric model can explain that it can be used to implement changeover switches, where it can modulate different targets at different calcium concentrations. In particular, allosteric properties of calmodulin may suffice to explain the differential activation of calcineurin, leading to synaptic long-term depression, and calcium/calmodulin kinase II, leading to synaptic long term potentiation, a molecular basis of learning and memory. Because the concentration of calmodulin in neurons is of the same order of magnitude than the dissociation constants for calcium, it is subjected to a phenomenon called "ligand depletion". Amplified in cooperative systems, this phenomenon causes the dynamic range and the cooperativity of response to calcium to be different in different neurons. Ligand-depletion also provide a mechanism to quickly fine-tune the dynamic of response to environmental signals. References: Stefan M.I., Edelstein S.J., Le Novère N. An allosteric model of calmodulin explains differential activation of PP2B and CaMKII. Proc Natl Acad Sci USA (2008), 105: 10 768-10773. Stefan M.I., Edelstein S.J., Le Novère N. Computing phenomenologic Adair-Klotz constants from microscopic MWC parameters. BMC Sys Biol (2009), 3: 68. Edelstein S.J., Stefan M.I, Le Novère N. Ligand depletion in vivo modulates the dynamic range of cooperative signal transduction. PLoS ONE (2010), 5(1): e8449.

Présentation donnée dans le cadre du cours pasteurien «Sécurité Sanitaire des Aliments et Analyse de Risque» co-dirigé par Jean-Christophe Augustin et Régis Pouillot

Résumé
Bacillus cereus est une bactérie pathogène de l’insecte et un pathogène opportuniste émergent pour l’homme. L’approche IVET (In Vivo Expression Technology) a été utilisée chez B. cereus pour identifier des gènes qui s’expriment spécifiquement au cours de l’infection chez l’insecte. Une protéine désignée IlsA (Iron-dependent Leucine-rich Surface protein), est activée par une carence en fer in vitro et aussi in vivo, mais uniquement dans l’hemocoel. L’immuno-marquage a montré qu’IlsA est présente à la surface bactérienne. L’inactivation d’ilsA conduit à une diminution de la virulence de B. cereus chez l’insecte et la souche dépourvue d’IlsA ne peut plus utiliser l’hème, l’hémoglobine et la ferritine comme sources de fer pour sa croissance. Il est remarquable qu’IlsA se lie à l’hémoglobine ainsi qu’à la ferritine, deux molécules chimiquement distinctes. Ceci suggère qu’IlsA a un rôle essentiel dans l’adaptation aussi bien chez les hôtes invertébrés que vertébrés.

SEMINAIRE DU DEPARTEMENT D'IMMUNOLOGIE

Présentation donnée dans le cadre du cours pasteurien «Sécurité Sanitaire des Aliments et Analyse de Risque» co-dirigé par Jean-Christophe Augustin et Régis Pouillot

University of Oxford (Department of Biochemistry), UK Johns Hopkins University, School of Medicine (Dept. of Physiology), Baltimore MD, USA

Séminaire du Département de Biologie Cellulaire et Infection

SEMINAIRE DU DEPARTEMENT DE VIROLOGIE

SEMINAIRE DU DEPARTEMENT DE VIROLOGIE

Abstract:
Genomic islands are considered important components of bacterial genomes with a history of horizontal acquisition. Some genomic islands are still actively mobile, and their program of activation and cell maintenance is interesting to study and compare to, for example, phages and plasmids. Here I will describe our current attempts to unravel the life-style program of the ICEclc genomic island in Pseudomonas, a program invoking bistable phenotypic differentiation and cell death.

Department of Biochemistry
Faculty of Biology and Medicine
University of Lausanne
Switzerland

Séminaire organisé par le département de Microbiologie

SEMINAIRE DU DEPARTEMENT D'IMMUNOLOGIE

SEMINAIRE DU DEPARTEMENT DE VIROLOGIE

Center for Global Health, Division of Infection Diseases and International Health, University of Virginia, Charlottesville, USA

SEMINAIRE DU DEPARTEMENT DE VIROLOGIE

Responsable de l’unité Défense innée et Inflammation / Inserm U874

Abstract :
DNA repair is an essential process for preserving genome integrity. Among the various forms of DNA damage, double-strand breaks (DSBs) are the most cytotoxic and genotoxic. To repair them, eukaryotic organisms use homologous recombination (HR): it consists of exchanging DNA strands between the broken DNA and an intact homologous DNA and it is choreographed by multi-protein complexes (1). During the first step of HR, Rad51 proteins polymerize on the broken DNA to form a nucleoprotein filament, this Rad51-DNA complex is then able to search for an intact homologous sequence among the whole genome and to perform strand exchange. We will present in vitro and in vivo approaches to characterize the different steps of homologous recombination. To investigate the polymerization and the strand exchange steps, we used magnetic tweezers. We characterized the assembly and disassembly of hRad51 nucleoprotein filaments and measure the dynamic of strand exchange. To explore the step of homology search, we then developed an in vivo assay in yeast to visualize the dynamic of two homologous chromosomes in the absence and in the presence of a DSB. We observed that homologous chromosomes undergo a confined Brownian motion and that the two homologous DNA become highly dynamic during homology search.

SEMINAIRE DU DEPARTEMENT D'IMMUNOLOGIE

SEMINAIRE DU DEPARTEMENT D'IMMUNOLOGIE

Séminaire du Département de Biologie Cellulaire et Infection

Abstract:
To begin, I will present our vision of the opportunities for biologically inspired materials for applications ranging from thermal management in green buildings to pharmacology and studies of tissue-scale biological processes. I will point to the central role of microvascular structure – for the transmission of mass, energy, and stress – within these materials. With an overview of design considerations, I will introduce our methods to form vascularized synthetic materials with microfabrication tools that we have adapted for use in biologically compatible hydrogels . As a first example of function, I will present our successful effort to test and apply the cohesion-tension theory of transpiration in vascular plants within, “synthetic trees” . I will discuss the physiological significance of our findings and point out the opportunities to investigate other aspects of water management in plants, such as recovery after cavitation. As a second example, I will present our development of scaffolds for mammalian tissue culture with embedded microfluidic structure . I will show how this artificial vasculature allows for the definition of well-defined distributions of solutes and the extraction of metabolic information within 3-D cultures. Finally, I will give an overview of our current studies of vasculogenic and angiogenic processes in vitro with the goal of forming native-like microvessels that can remodel under the influence of externally applied physical and biological stimuli.

( ** Séminaire du Département de Biologie Structurale et Chimie / DBSC ** )

SEMINAIRE DU DEPARTEMENT D'IMMUNOLOGIE

Séminaire du Département de Biologie Cellulaire et Infection

SEMINAIRE DU DEPARTEMENT D'IMMUNOLOGIE

Responsable de l’unité de recherche et d’Expertise Epidémiologie des Maladies Emergentes

SEMINAIRE DU DEPARTEMENT D'IMMUNOLOGIE

Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases, Harvard Medical School, Boston SEMINAIRE DU DEPARTEMENT DE VIROLOGIE

Séminaire du Département de Biologie Cellulaire et Infection