3 ème Colloque «Montpellier Infectious Diseases» Pôle Rabelais

Size: px
Start display at page:

Download "3 ème Colloque «Montpellier Infectious Diseases» Pôle Rabelais"

Transcription

1 3 ème Colloque «Montpellier Infectious Diseases» Pôle Rabelais novembre 2014 Genopolys Livre de résumés

2 Session 1 - Infection, transmission and drug design. 1

3 Chromosomal DNA replication and segregation in Leishmania Yvon Sterkers 1, Slavica Stanojcic Etienne Schwob Michel Pagès 1, Patrick Bastien 1, 1 : Laboratoire de Parasitologie-Mycologie, Montpellier (MIVEGEC) - Site web Université Montpellier II - Sciences et techniques, CNRS : UMR5290, Institut de recherche pour le développement [IRD] : UR224, CHRU Montpellier, Université Montpellier I 39, Avenue Charles Flahault, Montpellier - France 2 : Institut de génétique moléculaire de Montpellier (IGMM) - Site web CNRS : UMR5535, Université Montpellier II - Sciences et techniques 1919 Route de Mende MONTPELLIER CEDEX 5 - France * : Auteur correspondant In most biological models, reproduction as identical or similar organisms is based on the extreme accuracy of the mechanisms involved in the even transmission of the genetic material to the two daughter cells. This 'golden rule' does not seem to apply in Leishmania in which asymmetric chromosomal allotments during mitosis are responsible for a unique ploidy organization termed 'mosaic aneuploidy'. To get further insight into this unique feature, we developed an interest in chromosomal replication and segregation which are ill-known in Leishmania. We also studied the 'sister parasite' Trypanosoma brucei, which is diploid and where these key cellular processes are better elucidated. We followed two independent research approaches. First, to determine the physical parameters of the replication process, we analysed DNA replication dynamics in these parasites using DNA molecular combing; this allowed showing particularly large inter-origin distances and high speeds of DNA replication forks. Second, we studied the chromosomal dynamics during mitosis. Using fluorescent in situ hybridization combined with immunofluorescence in T. brucei procyclic forms, we determined the spatiotemporal dynamics of (i) the centromeres of chromosome II and III, and (ii) TbMlp2, the ortholog of a nucleoporin, during the course of the cell cycle. In interphase, the centromeres and TbMlp2 were located at the periphery of the nucleolus. TbMlp2 was then seen progressively migrating from the periphery of the nucleolus to the spindle poles. The position of the centromeres remained unchanged until TbMlp2 had completed migration to the spindle pole; then the centromeres themselves started migrating to the poles. In addition, RNAi knockdown of TbMlp2 lead to aneuploidy. Altogether, these data suggest that, unexpectedly, TbMlp2 may play a key role, as a molecular chaperone and/or transport protein, in the dynamics of chromosomal segregation. In total, both approaches again revealed original features in these divergent eukaryotes as compared to classical models. 2

4 Wolbachia interactions with its filarial nematode host: transmission mechanisms and roles of the symbiont. Frederic Landmann 1 : Centre de Recherche de Biochimie Macromoléculaire (CRBM) - Site web CNRS : UMR5237 CNRS-UMR , Route de Mende Montpellier Cedex 5 FRANCE - France Wolbachia are gram-negative, obligate, intracellular bacteria carried by millions of arthropods worldwide. Wolbachia are also symbiotic with filarial nematodes, but exclusively with members of the parasitic Onchocercidae family. Wolbachia are transmitted vertically through the female germline, similar to mitochondria. In nematodes, the Wolbachia-host symbiosis has evolved toward mutualism and bacteria removal interferes with worm development and eventually leads to nematode death. Filarial nematodes are causative agents of devastating diseases such as elephantiasis and river blindness. These diseases affect ~120 million people in tropical areas. There is currently no drug treatment against adult filarial nematodes. Because Wolbachia is essential to adult worm survival and fertility, Wolbachia is a promising drug target. Using Brugia malayi as a filarial model, a causative agent of elephantiasis, we are focusing on two fundamental aspects of this symbiosis : - the mechanisms of Wolbachia transmission, from the fertilized egg to the adult tissues. - the role and contribution of symbionts to the filarial host. Using cell biology techniques we designed for studying these parasitic worms, we show that Wolbachia asymmetrically segregate during embryogenesis to reach only the hypodermis of the worm, and an ovarian tropism allows the symbionts in the hypodermis to colonize the adult female germline. We will present the defects induced during oogenesis and embryogenesis in the absence of Wolbachia. 3

5 Identification of inhibitors of PfCCT, a key enzyme of Plasmodium falciparum membrane biosynthesis Alicia Contet Ewelina Guca 1, Emilie Pihan Marina Lavigne François Hoh Jean-François Guichou Henri Vial Dominique Douguet Rachel Cerdan 1 : Dynamique des interactions membranaires normales et pathologiques (DIMNP) - Site web CNRS : UMR5235, Université Montpellier I, Université Montpellier II - Sciences et techniques BT 24 CC 107 Place Eugène Bataillon MONTPELLIER CEDEX 5 - France 2 : Centre de Biochimie Structurale (CBS) - Site web Inserm : U1054, Université Montpellier II - Sciences et techniques, CNRS : UMR5048, Université Montpellier I 29 rue de Navacelles MONTPELLIER Cedex - France - France 3 : Institut de pharmacologie moléculaire et cellulaire (IPMC) - Site web CNRS : UMR7275, Université Nice Sophia Antipolis (UNS) CNRS-IPMC 660 Route des lucioles VALBONNE - France During its life cycle in the human erythrocyte, Plasmodium falciparum, the parasite responsible of malaria, relies on phospholipids to build the membranes necessary for daughter cell development. The parasite membranes are composed of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) which together represent approx. 80% of the total membrane lipids. In P. falciparum, PC and PE are synthesized by the parasite's machinery through the de novo CDP-choline and CDP-ethanolamine (Kennedy) pathways using choline or ethanolamine as precursors. Our studies focus on the two cytidylyltransferases : PfCCT and PfECT. These enzymes catalyze the rate-limiting step of their respective pathway and both contain two cytidylyltransferase domains. Here we focus on the biochemical characterization and the inhibition of PfCCT. Interestingly, both catalytic domains of PfCCT are active while site-directed mutagenesis revealed that only one domain of PfECT is active, suggesting substantial evolutionary differences within this protein family3. Recently, we obtained the 3D crystal structure at 2.4 Å resolution of the C-terminal catalytic domain of PfCCT in complex with its reaction product CDP-choline. By virtual screenings of commercial compounds using docking tools, we identified molecules that competitively inhibit PfCCT activity. We are also developing a second approach for the identification of PfCCT inhibitors by fragment-based drug design. Primary screening of fragment library (230 molecules) has been performed by fluorescence-based thermal shift assay followed by Nuclear Magnetic Resonance Saturation Transfer Difference (NMR STD) as secondary screen to eliminate false positive ligands. Cocrystallization of the protein-fragments complexes will then be used for the optimization process, allowing subsequent rational design of inhibitors of this key enzyme of P. falciparum membrane biosynthesis. 4

6 Rationnal Design of small-molecules inhibitors of human Cyclophilins and HCV replication by Structure Based Drug Design. Jean-François Guichou 1, Jean-Michel Pawlotsky 1 : Centre de Biochimie Structurale Inserm : U554, CNRS : UMR5048, Université Montpellier I, Université Montpellier II - Sciences et Techniques du Languedoc 2 : Centre de Biochimie Structurale (CBS) Inserm : UMR : hopital henri mondor Hôpital Henri Mondor The hepatitis C virus (HCV) is the leading cause of chronic hepatitis, of liver cirrhosis and hepatocellular carcinoma. Roughly 170 millions individuals are infected in the whole world and the infection by HCV causes approximately deaths per year. The study of the complex of replication made it possible to highlight the crucial role of cellular partners, in particular the cyclophilins1, in the driving process with the synthesis of new viral genomes and inhibition of these enzymes lead to new anti-viral agents. The Cyclophilins are enzymes that have been observed abundantly and ubiquitously in a wide range of tissue types and organisms. They are characterized by the ability to catalyse the cis-trans isomerisation of peptidylprolyl bonds2 (PPIases) which was identified as the rate-limiting step in protein folding. To design news Cyps inhibitors with low molecular mass, we applied a fragmentbased screening approach on Cyclophilin D (CypD). We used X-ray crystallography and NMR that are well adapted to identify weak affinity fragments (mm). We solved 14 crystallographic structures of CypD in complex with fragments (2,00-0,97Å). Based on the fragments binding modes, we designed and optimized a new Cyps inhibitors family (proline mimetic). Our lead compound have an IC50 of 10 nm on CypD and CypA in vitro and an EC50 of 15 nm for the HCV replication in cellulo. The presentation will show the used of X- ray crystallography for the discovery of news human Cyps and HCV inhibitors. [1] Rice M.C., Top. Antivir. Med., 2011, 19(3): [2] Galat, A., Eur J Biochem, 1993, 216 :

7 Investigation of capsid determinants involved in nepovirus transmission: a hybrid structural approach Patrick Bron 1 : Centre de Biochimie Structurale (CBS) - Site web Inserm : UMR1054, CNRS : UMR5048, Université Montpellier II - Sciences et Techniques du Languedoc, Université Montpellier I 29 rue de Navacelles MONTPELLIER Cedex - France - France Arabis mosaic virus (ArMV) and Grapevine fanleaf virus (GFLV) are two picorna-like viruses from the genus Nepovirus, consisting in a bipartite RNA genome encapsidated into a 30 nm icosahedral viral particle formed by 60 copies of a single capsid protein (CP). They are responsible for a severe degeneration of grapevines that occurs in most vineyards worldwide. Although sharing a high level of sequence identity between their CP, ArMV is transmitted exclusively by the ectoparasitic nematode Xiphinema diversicaudatum whereas GFLV is specifically transmitted by the nematode X. index. The structural determinants involved in the transmission specificity of both viruses map solely to their respective CP. We present here a structural study that allowed us to identify a charged pocket involved in specificity of transmission of Nepovirus by hybrid approach combining X-ray crystallography, cryoelectron microscopy, single particle analysis and molecular dynamics methods. 6

8 The Two Human CXCR4 Isoforms Display Different HIV Receptor Activities: Consequences for the Emergence of X4 Strains Charline Duquenne Christina Psomas Sandrine Gimenez Adeline Guigues Marie-Josée Carles Claudine Barbuat Jean-Philippe Lavigne Albert Sotto Jacques Reynes Paul Guglielmi Clément Mettling Vincent François Pierre Corbeau 1 : IGH CNRS : UPR : CHU Montpellier CHU Montpellier 3 : CHU Nîmes CHU Nîmes 4 : UM2 UM2 5 : IGH CNRS : UPR1142, CNRS CXCR4 is a chemokine receptor that plays key roles with its specific ligand, CXCL12, in stem cell homing and immune trafficking. It is also used as a coreceptor by some HIV-1 strains (X4 strains), whereas other strains (R5 strains) use an alternative coreceptor, CCR5. X4 strains mainly emerge at late stages of the infection and are linked to disease progression. Two isoforms of this coreceptor have been described in humans, CXCR4-A and CXCR4-B, corresponding to an unspliced and a spliced mrna, respectively. Here, we show that CXCR4-B, but not CXCR4-A, mediates an efficient HIV-1 X4 entry and productive infection. Yet, the chemotactic activity of CXCL12 on both isoforms was similar. Furthermore, HIV-R5 infection favored CXCR4-B expression over that of CXCR4-A. In vitro infection with an R5 strain increased CXCR4-B : CXCR4-A mrna ratio in peripheral blood mononuclear cells (PBMC), and this ratio correlated with HIV RNA plasma level in R5-infected individuals. In addition, the presence of the CXCR4-B isoform favored R5 to X4 switch more efficiently than CXCR4-A in vitro. Hence, the predominance of CXCR4-B over CXCR4-A expression in PBMC was linked to the capability of circulating HIV-1 strains to use CXCR4, as determined by genotyping. These data suggest that R5 to X4 switch could be favored by R5 infectioninduced overexpression of CXCR4-B. Finally, we achieved a specific sirna-mediated knockdown of CXCR4-B. This represents a proof of concept for a possible gene therapeutic approach aimed at blocking the HIV coreceptor activity of CXCR4 without knocking down its chemotactic activity. 7

9 Session 2 - Infection, immunity and regulation 8

10 Identification and characterization of Mabs_4780, a new determinant required for intracellular survival and pathogenicity of Mycobacterium abscessus Iman Halloum 1, Séverine Carrère-Kremer Vipul Singh Audrey Bernut Georges Lutfalla Laurent Kremer 1 : Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques (DIMNP) - Site web CNRS : UMR5235 CNRS-Université de Montpellier II Montpellier cedex 5 - France 2 : Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques (DIMNP) CNRS : UMR : Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques CNRS : UMR : Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques (DIMNP) - Site web CNRS : UMR5235 Université Montpellier 2 Bât 24 2 étage Place Eugène Bataillon Montpellier cedex 5 France - France * : Auteur correspondant Mycobacterium abscessus (Mabs) is an emerging rapid-growing mycobacteria causing severe lung infections, particularly in cystic fibrosis patients. The smooth morphotype displays surface expression of glycopeptidolipids (GPLs) whereas the rough morphotype is characterized by the loss of surface GPL. Rough variants are involved in more severe clinical forms although the underlying physiopathological mechanisms remain obscure. We have recently developed a zebrafish embryo model to decipher the pathogenesis of Mabs and the chronology of the infection process. Herein, we evaluated the contribution of MABS_4780 in rough Mabs virulence. A mutant was constructed in which MABS_4780 was disrupted by a hygromycin cassette. This strain exhibited a higher susceptibility to thiacetazone, a second-line antitubercular drug, compared to the parental strain and higher sensitivity to detergents, presumably due to alterations of cell wall composition/structure. Consistent with hypothesis, solving the three-dimensional structure of the M. smegmatis orthologue revealed a MaoC-like structure of known dehydratases, potentially involved in cell wall lipid biosynthesis. Since Amoeba may represent the environmental reservoir of Mabs, we also assessed the intracellular fate of the mutant in Acanthamoeba Castellanii. The mutant failed to replicate intracellularly but this growth defect was not due to a general metabolic abnormality since it grew similarly to parental strain in vitro. In addition, unlike the R variant, the mutant strain was extremely attenuated in infected zebrafish embryos and was unable to produce abscesses within the central nervous system and to kill the embryos. Our findings demonstrate the unanticipated role of MABS_4780 in physiopathology of Mabs infection, emphasizing its potential as an attractive drug target. 9

11 Phosphorylation of proteins and bacterial pathogenicity Virginie Molle 1 : UMR5235 (DIMNP) - Site web CNRS, UM2 DIMNP-University Montpellier 2 Place Eugene Bataillon Montpellier - France The importance of reversible protein phosphorylation to cellular regulation cannot be overstated. In eukaryotic cells, protein kinase/phosphatase signaling pathways regulate a staggering number of cellular processes including cell proliferation, cell death, metabolism, behavior and neurological function, development and pathogen resistance. While protein phosphorylation as a mode of eukaryotic cell regulation is familiar, many are less familiar with protein kinase/phosphatase signaling networks that function in prokaryotes. Of particular interest, the persistence of bacterial infections in humans and the emergence of antibiotic-resistant strains emphasize the need for novel therapeutic approaches. In order to sustain treatment of bacterial infections in humans, identification of novel drug targets is pivotal. Thus, a greater understanding of molecular mechanisms underlying bacterial disease pathogenesis is essential for the identification and further development of novel drug targets. The discovery of eukaryotic-like signaling systems, such as STPKs (Serine/Threonine Protein Kinases) and phosphatases in bacterial pathogens has sparked an interest in understanding their function. This is partly due to the fact that eukaryotic protein kinases are currently the largest group of drug targets, second only to G-protein-coupled receptors. Therefore, studies on the importance of prokaryotic STPKs in human pathogens have gained interest owing to the prospect that these signaling components may be useful in future anti-infective therapies and that a complete understanding of their role is a prerequisite for future evaluation of these enzymes as antimicrobial targets. The increased understanding of their widespread occurrence and the importance of the processes they control emphasize the significance of these eukaryotic-like signaling systems in prokaryotes and especially in pathogens. Although STPKs and phosphatases regulate important functions in bacterial pathogens, our understanding of the signal transduction mechanism is still in its infancy. The contribution of these signaling enzymes to bacterial growth and pathogenesis is multifaceted as can be expected for any signaling system. In our group, we are exploring the mechanism for how these signaling enzymes mediate diverse functions in a coordinated fashion as it remains to be completely understood. 10

12 Host immune response and macrophage behaviour during Burkholderia cepacia complex infection in zebrafish embryos Jennifer Mesureur Annemarie Meijer Annette Vergunst 1 : Virulence Bactérienne et Maladies Infectieuses Inserm : U1047, Université Montpellier I UFR Médecine, CS , chemin du carreau de Lanes NIMES Cedex 02 - France 2 : Gorlaeus Laboratory Institute of Biology, Leiden University Gorlaeus Laboratory, Cell Observatory, Einsteinweg 55, 2333 CC Leiden, The Netherlands - Pays-Bas 3 : Virulence Bactérienne et Maladies Infectieuses Inserm : U1047, Université Montpellier I UFR Médecine, CS , chemin du carreau de Lanes NIMES Cedex 02 France - France Chronic respiratory infection in cystic fibrosis patients is characterized by a high level of proinflammatory cytokines, leukocyte infiltration, and inflammation in the lungs due to colonization by pathogenic bacteria. Chronic infections caused by bacteria belonging to the Burkholderia cepacia complex (Bcc) can be symptom free, but often cause pulmonary exacerbation with progressive worsening of lung function, sometimes resulting in acute fatal necrotizing pneumonia and sepsis. The reasons for these unpredictable, sudden transitions are not understood. Using zebrafish embryos, which have an innate immune system very similar to that of humans, we previously found that B. cenocepacia K56-2, belonging to the epidemic ET12 lineage, is highly virulent for zebrafish embryos; it causes a rapidly fatal (2 days) systemic inflammatory infection. In contrast, embryos can control infection with strains such as B. stabilis LMG14294, which cause a persistent infection. Intravenously injected bacteria are rapidly phagocytosed by macrophages, and we found that an intracellular stage is important for fatal infection. In an attempt to better understand the molecular basis for B. cenocepacia K56-2 or B. stabilis LMG14294 infection outcomes, we performed a global host transcriptome analysis during different stages of both infection types. RNA-seq analysis revealed interesting infection responsive host gene expression patterns. Whereas many host genes were differentially regulated during early (3 hours) as well as later (24 hours) stages of infection caused by B. cenocepacia K56-2, only few genes showed changes in expression level upon persistent infection with B. stabilis LMG In particular, the innate immune response with Toll-like receptor (TLR), NOD-like receptor and apoptosis pathways were strongly activated during acute infection. The silent intracellular persistence of B. stabilis coincided with increased expression of genes encoding complement proteins. We will discuss how we are using the zebrafish model to further study the role of the TLR pathway, including the central adaptor protein MyD88 and intracellular stages in the induction of the highly excessive innate inflammatory response. 11

13 Role of the transcriptional regulator RegA in establishment of Brucella suis persistence in an original in vitro model Elias Elias Abdou1, Ignacio Martinez-Abadia1, Véronique Pantesco2, Sascha Al Dahouk3, Stephan Köhler1, Veronique Jubier-Maurin1 1, 2, 1 : 1Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR5236 CNRS; Université Montpellier 1 ; Université Montpellier 2 CNRS : UMR : 2Institute for Research and Biotherapy, CHU Saint-Eloi, Inserm U1040, Montpellier Centre de Recherche Inserm 3 : 3Federal Institute for Risk Assessment, Berlin, Germany (BFR) Berlin - Allemagne Oxygen deficiency is one of the environmental conditions encountered by Brucella during intramacrophagic replication and chronic infection of the host. At chronic stage of brucellosis, these bacteria can reside in immune structures where anoxic conditions predominate. Our previous studies demonstrated the high metabolic flexibility of Brucella suis with respect to oxygen deprivation. We evidenced the central role of the two-component system RegB/RegA in the coordinated control of oxidative respiration and denitrification respiratory systems, which are crucial for virulence and/or persistence in vivo. More importantly, RegA was found to be essential for B. suis persistence in mice. Recently, we developed an original in vitro model, characterized by progressive oxygen deprivation, which allowed to show that RegA is essential for optimal long-lasting in vitro persistence. To identify RegA-dependent genes and proteins in this model, global transcriptome analysis and whole proteome quantifications were performed by comparison of the wild-type B. suis to a rega mutant strain. These analyses were performed at the time point where anaerobic conditions become established, corresponding to the cessation of wild-type strain multiplication. Genetic validation by quantitative PCR (RT-qPCR) indicated that RegA potentially regulates 12% of the B. suis genes. The down-regulation of genes or proteins involved in cell envelope biogenesis and in cellular division suggests that RegA could be involved in establishment of a non-replicative state. In addition, RegA-dependent repression of an important number of genes involved in energy production may be indicative of a participation of RegA in the slowing-down of central metabolim as it enters into the persistence phase. This was substantiated by the finding that two-thirds of the differentially produced proteins belonging to this functional class were also found repressed, among which isocitrate lyase, the first enzyme of the glyoxylate shunt. Several genes of the virb operon were also found repressed by RegA as was its regulator VjbR. In conclusion, RegA was found to regulate genes that encode proteins of all functional groups. This makes the two-component system RegB/RegA a main regulatory system required for adaptation of B. suis to oxygen depletion, which can contribute to the constraint of bacterial growth, characteristic of chronic infection. 12

14 Characterization of RbpA a master regulator of gene expression from Mycobacterium tuberculosis Ayyappasamy Sudalaiyadum Perumal Rishi Kishore Vishwakarma Zakia Morichaud Francoise Roquet-Baneres Konstantin Brodolin 1, 1 : Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) - Site web Centre d études d agents Pathogènes et Biotechnologies pour la Santé CPBS - UMR 5236 / CNRS - UM1 / UM route de Mende MONTPELLIER Cedex 5 - France * : Auteur correspondant RbpA, a RNA polymerase binding transcriptional activator protein from Mycobacterium tuberculosis (Mtb), regulates transcription without binding to the double stranded DNA. RbpA is involved in unwinding of the promoter DNA in transcription complexes containing either the housekeeping sigma factor sigma A (σa) or the stress-response sigma factor sigma B (σb). RbpA, predominantly found in actinomycetes, increases the tolerance levels to antibiotics including Rifampicin, most commonly used antibiotic against tuberculosis (the second infection causing highest number of deaths). By using the in-vitro transcription system (IVTS) and electrophoretic mobility shift assays (EMSA), we showed that the action of RbpA is sequence specific, as transcription from the housekeeping sigap promoter of Mtb requires RbpA for activation, but another housekeeping promoter of B. subtilis, sinp3 doesn't require RbpA for the activation. Furthermore, series of mutations of the nucleotides upstream of the sigap promoter suppressed the promoter dependency on RbpA. Thus, the fact that RbpA is involved in RNA polymerase - σa and σb mediated transcriptional activation and increased tolerance to rifampicin, corroborates its role in global regulation of the antibiotic-induced stress in Mycobacterium. Hence, a new approach for Mtb, known as Run-off microarray (ROMA), has been elaborated using in-vitro transcription on genomic DNA, for studying the genome-wide regulation of the gene expression by RbpA. 13

15 Life Technologies - Technologies CRISPR/TALS (genome editing), nouvelles stratégies de clonage et synthèse de gène Chady Jaber 1, Andy Tempez 1 : Life Technologies Thermo Fisher Scientific * : Auteur correspondant CRISPRs and TALs are innovative technologies for genome editing. They provide the ability to target, edit and regulate expression at defined sequences within the genome and enable researchers to more accurately study and engineer gene function and develop better cell models. Life Technologies offers a unique flexibility and accessibility to these technologies through its customized solutions. Furthermore, Life Technologie propose powerful and versatile cloning and expression vectors, GeneArt gene synthesis and assembly tools, and molecular biology essentials for that critical first step in your experiment. Experience the full GeneArt portfolio for your molecular biology projects and outperform conventional techniques in many aspects from time and economization to expression optimization, stability and quality. 14

16 Session 3 - Epidemiology, clinical trials and emerging pathogens 15

17 Dynamic of the Hand, Foot and Mouth Disease in Hai Phong city, Vietnam Patrice Ravel 1, Nghia Ngu Duy 2, Laurent Gavotte 3, Emmanuel Cornillot 1,4,*, Roger Frutos 1,5,* 1 : Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR5236 CNRS, UM1, UM2, Montpellier, France 2 : NIHE - National Institute of Hygiene and Epidemiology, Ho Chi Minh, Vietnam. 3 : Institut des Sciences de l'evolution - Montpellier (ISEM) UMR5554 CNRS, IRD, UM2 4 : Institut de Biologie Computationnelle, Montpellier, France 5 : CIRAD - Centre de coopération internationale en recherche agronomique pour le développement (TA-A17/G), Baillarguet, France * : Auteur correspondant Contact : Hand, foot and mouth disease (HFMD) is an acute febrile illness in children with a papulovesicular skin rash at the palms or soles of the feet, or both. HFMD is caused by members of Human Enterovirus A family of viruses which include Coxsackievirus A (CVA) and Human Enterovirus 71 (EV71). A large scale HFMD epidemic was reported for the first time between 2011 and 2012 in Northern Vietnam. We focus our attention on the large cityharbour of Hai Phong. Two main aspects were studied. The first consisted of determining and understanding the high level of diversity of the clinical signs using the three most solid clinical quantitative parameters; i.e., age, severity score and delay of time of onset to admission from the clinical data set of the observed cases. A hierarchical classification approach was used to cluster the patients into groups of common symptoms and analyze their distribution over the span of the epidemic. The second consisted in analyzing the spread of HFMD according to time and space. The commune is the smallest subdivision of Hai Phong City. Using the commune for geographical localization and the time distribution of the detected cases, recording was done in Geographic Information System (QGIS). The data were used to create a graph that modelised the outbreak of HFMD. Numerical analyses were investigated to determine some group of communes that presented similarities concerning the spatial dynamic of HFMD.* 16

18 HIV patients under suppressive antiretroviral therapy present with various patterns of immune activation: the ACTIVIH study Christina Psomas Mehwish Younas Renaud Cezar Edouard Tuaillon Claudine Barbuat Erika Nogue Christelle Reynes Pierre Portales Pierre Corbeau Jacques Reynes 1 : CHU Montpellier CHU Montpellier 2 : CHU Nîmes CHU Nîmes 3 : EA 2415 UM1 4 : IGH CNRS : UPR1142 Background: HIV infection induces an immune activation fuelled by several causes that may occur in various combinations. These causes are reduced under highly active antiretroviral therapy (HAART), but usually not abolished. In the ACTIVIH study, we analyzed whether immune activation is qualitatively the same for all efficiently treated patients or whether different patterns of immune activation may be identified. Methods: To this aim, we measured in 120 HIV-positive adults, aviremic under HAART for at least 2 years, 55 cell surface and soluble markers of inflammation, and CD4+ T cell, CD8+ T cell, B cell, NK cell, monocyte, and neutrophil activation. We clustered the dataset using two independent hierarchical clustering analyses: one for variables using the 1-r² (where r is the linear correlation coefficient) as a distance between variables, and one for observations using usual Euclidean distance measured on scaled variables for observations. Results: The level of many markers of immune activation were increased, but not altogether in a given patient. We identified various subpopulations of patients according to their pattern of immune activation (Figure). Using ANOVA results corrected by False Discovery Rate for multiple testing, more than 90% of variables were on average significantly different for at least one subpopulation of patients with regards to the other ones (p-value < 0.05). Conclusions: These different patterns of immune activation may be the result of different causes, and may result in different pathogenic consequences. A better understanding of the links between causes, patterns, and consequences of immune activation in virologic responders might pave the way to the identification of markers predictive of specific comorbidities, and to an etiologic and/or symptomatic immunosuppressive therapeutic approach tailored to each subpopulation of patients. 17

19 Gender differences in adherence and response to antiretroviral treatment in the Stratall trial in rural disctrict hospitals in Cameroon Charlotte Boullé Charles Kouanfack Gabrièle Laborde Balen Avelin Agkokeng Maria Patrizia Carrieri Serge Kazé Marlise Dontsop Jean-Marc Mben Sinata Koulla-Shiro Gilles Peytavin Bruno Spire Eric Delaporte Christian Laurent 1 : UMI VIH/SIDA et maladies associées (TransVIHMI) - Site web Université Cheikh Anta Diop (Dakar, Sénégal), Universtié Yaoundé 1 (Cameroun), Université Montpellier I, Institut de recherche pour le développement [IRD] : UR233 Centre IRD France Sud 911, avenue Agropolis BP F Montpellier cedex 5 - France 2 : INSERM U912 SESSTIM, Université Aix Marseille Université de la Méditerranée - Aix-Marseille II 3 : Hopital Central de Yaoundé P- P pital Bichat-Claude Bernard, Laboratoire de Pharmaco-Toxicologie, Paris Assistance publique - Hôpitaux de Paris (AP-HP), Institut National de la Santé et de la Recherche Médicale - INSERM Background: Evidence of gender differences in antiretroviral treatment (ART) outcomes in sub-saharan Africa is conflicting. Our objective was to assess gender differences in 1) adherence to ART and 2) virologic failure, immune reconstitution, mortality, and disease progression adjusting for adherence. Methods: Cohort study among 459 ART-na ve patients followed-up 24 months after initiation in in nine rural district hospitals. Adherence to ART was assessed using 1) a validated tool based on multiple patient self-reports and 2) antiretroviral plasma concentrations. The associations between gender and the outcomes were assessed using multivariate mixed models or accelerated time failure models. Results: One hundred thirty-five patients (29.4 %) were men. At baseline, men were older, had higher BMI and hemoglobin level, and received more frequently efavirenz than women. Gender was not associated with self-reported adherence (P=0.872, and for moderate adherence, low adherence and treatment interruption, respectively) or with antiretroviral plasma concentrations (P=0.549 for nevirapine/efavirenz). By contrast, male gender was associated with virologic failure (odds ratio 2.18, 95 %CI , P=0.003), lower immunologic reconstitution (coefficient at month 24, 95 %CI ;-16.6, P=0.006), and faster progression to death (time ratio [TR] 0.30, 95 %CI , P=0.014) and/or to WHO stage 4 event (TR 0.27, 95 %CI , P=0.017). Conclusions: Our study provides important evidence that African men are more vulnerable to ART failure than women and that the male vulnerability extends beyond adherence issues. Additional studies are needed to determine the causes for this vulnerability in order to optimize HIV care. However, personalized adherence support remains crucial. 18

20 Chikungunya virus-host interplay at the keratinocyte level Laurence 1 : Centre d études d agents Pathogènes et Biotechnologies pour la Santé (CPBS) CNRS UMR 5236, CNRS, CPBS, 1919 route de Mende F Montpellier, France. Université Montpellier 1, université montpellier 2, CNRS : UMR5236 Transmission of chikungunya virus (CHIKV) to humans is initiated by puncture of the skin by a blood-feeding Aedes mosquito. Despite the growing knowledge accumulated on CHIKV, the interplay between skin cells and CHIKV following inoculation still remains unclear. In this study we questioned the behavior of human keratinocytes, the predominant cell population in the skin, following viral challenge. We report that CHIKV rapidly elicits an innate immune in these cells leading to the enhanced transcription of type I/II and type III interferon genes. Concomitantly, we show that despite viral particles internalization into Rab5-positive endosomes and efficient fusion of virus and cell membranes, keratinocytes poorly replicate CHIKV as attested by absence of nonstructural proteins and genomic RNA synthesis. Accordingly, human keratinocytes behave as an antiviral defense against CHIKV infection rather than as a primary targets for initial replication. This picture significantly differs from that reported for Dengue and West Nile mosquito-borne viruses. 19

Understanding the immune response to bacterial infections

Understanding the immune response to bacterial infections Understanding the immune response to bacterial infections A Ph.D. (SCIENCE) DISSERTATION SUBMITTED TO JADAVPUR UNIVERSITY SUSHIL KUMAR PATHAK DEPARTMENT OF CHEMISTRY BOSE INSTITUTE 2008 CONTENTS Page SUMMARY

More information

The correct answer is c B. Answer b is incorrect. Type II enzymes recognize and cut a specific site, not at random sites.

The correct answer is c B. Answer b is incorrect. Type II enzymes recognize and cut a specific site, not at random sites. 1. A recombinant DNA molecules is one that is a. produced through the process of crossing over that occurs in meiosis b. constructed from DNA from different sources c. constructed from novel combinations

More information

GENETICS OF BACTERIA AND VIRUSES

GENETICS OF BACTERIA AND VIRUSES GENETICS OF BACTERIA AND VIRUSES 1 Genes of bacteria are found in bacterial chromosomes Usually a single type of chromosome May have more than one copy of that chromosome Number of copies depends on the

More information

WHY IS THIS IMPORTANT?

WHY IS THIS IMPORTANT? CHAPTER 12 THE STRUCTURE AND INFECTION CYCLE OF VIRUSES Eye of Science / Science Photo Library WHY IS THIS IMPORTANT? More than 80% of infectious diseases are caused by viruses. As a health professional,

More information

Pathogens and the immune system

Pathogens and the immune system Review of lecture 7 Pathogens and the immune system Veronica Leautaud, Ph.D. vl2@ rice.edu BRC 511 / 530-lab Lecture 8 BIOE 301-Bioengineering and World Health Science Science is the human activity of

More information

Recombinant DNA technology (genetic engineering) involves combining genes from different sources into new cells that can express the genes.

Recombinant DNA technology (genetic engineering) involves combining genes from different sources into new cells that can express the genes. Recombinant DNA technology (genetic engineering) involves combining genes from different sources into new cells that can express the genes. Recombinant DNA technology has had-and will havemany important

More information

Molecular Diagnosis of Hepatitis B and Hepatitis D infections

Molecular Diagnosis of Hepatitis B and Hepatitis D infections Molecular Diagnosis of Hepatitis B and Hepatitis D infections Acute infection Detection of HBsAg in serum is a fundamental diagnostic marker of HBV infection HBsAg shows a strong correlation with HBV replication

More information

Alison Stewart 11/12/06 Prokaryotic Cells, Eukaryotic cells and HIV: Structures, Transcription and Transport Section Handout Discussion Week #7

Alison Stewart 11/12/06 Prokaryotic Cells, Eukaryotic cells and HIV: Structures, Transcription and Transport Section Handout Discussion Week #7 Alison Stewart 11/12/06 Prokaryotic Cells, Eukaryotic cells and HIV: Structures, Transcription and Transport Section Handout Discussion Week #7 Compare and contrast the organization of eukaryotic, prokaryotic

More information

Understanding West Nile Virus Infection

Understanding West Nile Virus Infection Understanding West Nile Virus Infection The QIAGEN Bioinformatics Solution: Biomedical Genomics Workbench (BXWB) + Ingenuity Pathway Analysis (IPA) Functional Genomics & Predictive Medicine, May 21-22,

More information

Lecture 8. Protein Trafficking/Targeting. Protein targeting is necessary for proteins that are destined to work outside the cytoplasm.

Lecture 8. Protein Trafficking/Targeting. Protein targeting is necessary for proteins that are destined to work outside the cytoplasm. Protein Trafficking/Targeting (8.1) Lecture 8 Protein Trafficking/Targeting Protein targeting is necessary for proteins that are destined to work outside the cytoplasm. Protein targeting is more complex

More information

Opening Activity # 1: Opening Activity # 2: Latin Root Word #1: Latin Root Word #2: Review of Old Information: N/A New Information:

Opening Activity # 1: Opening Activity # 2: Latin Root Word #1: Latin Root Word #2: Review of Old Information: N/A New Information: Section: 1.4 Opening Activity # 1: Name: Opening Activity # 2: Latin Root Word #1: Latin Root Word #2: Review of Old Information: N/A New Information: Emerging Viruses: 1)West Nile Virus 2)HIV 3)Ebola

More information

Vitamin D and Control of Infectious Diseases

Vitamin D and Control of Infectious Diseases Vitamin D and Control of Infectious Diseases John H. White, Physiology and Medicine, McGill University Declaration: Nothing to Declare Disclosure I have no actual or potential conflict of interest in relation

More information

Recombinant DNA Technology

Recombinant DNA Technology PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R 8 Recombinant DNA Technology The Role of Recombinant DNA Technology in Biotechnology Biotechnology

More information

AP Biology Learning Objective Cards

AP Biology Learning Objective Cards 1.1 The student is able to convert a data set from a table of numbers that reflect a change in the genetic makeup of a population over time and to apply mathematical methods and conceptual understandings

More information

2.1.2 Characterization of antiviral effect of cytokine expression on HBV replication in transduced mouse hepatocytes line

2.1.2 Characterization of antiviral effect of cytokine expression on HBV replication in transduced mouse hepatocytes line i 1 INTRODUCTION 1.1 Human Hepatitis B virus (HBV) 1 1.1.1 Pathogenesis of Hepatitis B 1 1.1.2 Genome organization of HBV 3 1.1.3 Structure of HBV virion 5 1.1.4 HBV life cycle 5 1.1.5 Experimental models

More information

A Genetic Analysis of Rheumatoid Arthritis

A Genetic Analysis of Rheumatoid Arthritis A Genetic Analysis of Rheumatoid Arthritis Introduction to Rheumatoid Arthritis: Classification and Diagnosis Rheumatoid arthritis is a chronic inflammatory disorder that affects mainly synovial joints.

More information

Chapter 10 Manipulating Genes

Chapter 10 Manipulating Genes How DNA Molecules Are Analyzed Chapter 10 Manipulating Genes Until the development of recombinant DNA techniques, crucial clues for understanding how cell works remained lock in the genome. Important advances

More information

Chapter 22: The Lymphatic System and Immunity

Chapter 22: The Lymphatic System and Immunity Chapter 22: The Lymphatic System and Immunity Introduction Immune system the body s defenses against pathogens that produce disease 2 types of immunity Nonspecific immune mechanisms (Innate immunity) Provide

More information

Just the Facts: A Basic Introduction to the Science Underlying NCBI Resources

Just the Facts: A Basic Introduction to the Science Underlying NCBI Resources 1 of 8 11/7/2004 11:00 AM National Center for Biotechnology Information About NCBI NCBI at a Glance A Science Primer Human Genome Resources Model Organisms Guide Outreach and Education Databases and Tools

More information

specific B cells Humoral immunity lymphocytes antibodies B cells bone marrow Cell-mediated immunity: T cells antibodies proteins

specific B cells Humoral immunity lymphocytes antibodies B cells bone marrow Cell-mediated immunity: T cells antibodies proteins Adaptive Immunity Chapter 17: Adaptive (specific) Immunity Bio 139 Dr. Amy Rogers Host defenses that are specific to a particular infectious agent Can be innate or genetic for humans as a group: most microbes

More information

Bioinformatics: Network Analysis

Bioinformatics: Network Analysis Bioinformatics: Network Analysis Molecular Cell Biology: A Brief Review COMP 572 (BIOS 572 / BIOE 564) - Fall 2013 Luay Nakhleh, Rice University 1 The Tree of Life 2 Prokaryotic vs. Eukaryotic Cell Structure

More information

Chapter 20: Antimicrobial Drugs

Chapter 20: Antimicrobial Drugs Chapter 20: Antimicrobial Drugs 1. Overview of Antimicrobial Drugs 2. Antibacterial Drugs 3. Antiviral Drugs 4. Drugs for Eukaryotic Pathogens 1. Overview of Antimicrobial Drugs Antibiotics An antibiotic

More information

Structure and Function of DNA

Structure and Function of DNA Structure and Function of DNA DNA and RNA Structure DNA and RNA are nucleic acids. They consist of chemical units called nucleotides. The nucleotides are joined by a sugar-phosphate backbone. The four

More information

An Overview of Cells and Cell Research

An Overview of Cells and Cell Research An Overview of Cells and Cell Research 1 An Overview of Cells and Cell Research Chapter Outline Model Species and Cell types Cell components Tools of Cell Biology Model Species E. Coli: simplest organism

More information

and Antigen Presentation

and Antigen Presentation 1 Innate Immunity and Antigen Presentation Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Innate immunity Receptors and mechanisms Roles in disease Antigen

More information

Viral Infection: Receptors

Viral Infection: Receptors Viral Infection: Receptors Receptors: Identification of receptors has come from expressing the gene for the receptor in a cell to which a virus does not normally bind -OR- By blocking virus attachment

More information

New Approaches to a Major Public-Health Problem Infectious Diseases. Ethan Weiner, M.D. Senior Vice President Therapeutic Area Development Head

New Approaches to a Major Public-Health Problem Infectious Diseases. Ethan Weiner, M.D. Senior Vice President Therapeutic Area Development Head New Approaches to a Major Public-Health Problem Infectious Diseases Ethan Weiner, M.D. Senior Vice President Therapeutic Area Development Head Overview The Burden Of Infectious Disease Is Large And May

More information

IMMUNOLOGY STRUCTURE AND FUNCTION OF IMMUNE SYSTEM

IMMUNOLOGY STRUCTURE AND FUNCTION OF IMMUNE SYSTEM 59 IMMUNOLOGY STRUCTURE AND FUNCTION OF IMMUNE SYSTEM 59.1 INTRODUCTION The immune system is engaged in a constant surveillance of the body for pathogens or tumors. Whether disease develops depends on

More information

Autoimmunity and immunemediated. FOCiS. Lecture outline

Autoimmunity and immunemediated. FOCiS. Lecture outline 1 Autoimmunity and immunemediated inflammatory diseases Abul K. Abbas, MD UCSF FOCiS 2 Lecture outline Pathogenesis of autoimmunity: why selftolerance fails Genetics of autoimmune diseases Therapeutic

More information

What makes cells different from each other? How do cells respond to information from environment?

What makes cells different from each other? How do cells respond to information from environment? What makes cells different from each other? How do cells respond to information from environment? Regulation of: - Transcription - prokaryotes - eukaryotes - mrna splicing - mrna localisation and translation

More information

Student name ID # 2. (4 pts) What is the terminal electron acceptor in respiration? In photosynthesis? O2, NADP+

Student name ID # 2. (4 pts) What is the terminal electron acceptor in respiration? In photosynthesis? O2, NADP+ 1. Membrane transport. A. (4 pts) What ion couples primary and secondary active transport in animal cells? What ion serves the same function in plant cells? Na+, H+ 2. (4 pts) What is the terminal electron

More information

博 士 論 文 ( 要 約 ) A study on enzymatic synthesis of. stable cyclized peptides which. inhibit protein-protein interactions

博 士 論 文 ( 要 約 ) A study on enzymatic synthesis of. stable cyclized peptides which. inhibit protein-protein interactions 博 士 論 文 ( 要 約 ) 論 文 題 目 A study on enzymatic synthesis of stable cyclized peptides which inhibit protein-protein interactions ( 蛋 白 質 間 相 互 作 用 を 阻 害 する 安 定 な 環 状 化 ペプチドの 酵 素 合 成 に 関 する 研 究 ) 氏 名 張 静 1

More information

Nature of Genetic Material. Nature of Genetic Material

Nature of Genetic Material. Nature of Genetic Material Core Category Nature of Genetic Material Nature of Genetic Material Core Concepts in Genetics (in bold)/example Learning Objectives How is DNA organized? Describe the types of DNA regions that do not encode

More information

Chapter 12 - DNA Technology

Chapter 12 - DNA Technology Bio 100 DNA Technology 1 Chapter 12 - DNA Technology Among bacteria, there are 3 mechanisms for transferring genes from one cell to another cell: transformation, transduction, and conjugation 1. Transformation

More information

Virus Replication. Virus-Infected Cells. Virus Replication. Microbiology Lecture 6. Virus Replication in Tissue Culture.

Virus Replication. Virus-Infected Cells. Virus Replication. Microbiology Lecture 6. Virus Replication in Tissue Culture. Virus Replication Microbiology Lecture 6 Professor T.J. Foster Virus Replication Can causes many different changes to host cells Cytopathic Effects (CPE) Altered shape Lysis Membrane fusion (giant cell

More information

Innate Immunity: Nonspecific Defenses of the Host

Innate Immunity: Nonspecific Defenses of the Host 16 Innate Immunity: Nonspecific Defenses of the Host SLOs Differentiate between innate and adaptive immunity. Define toll-like receptors. Differentiate physical from chemical factors, and list examples

More information

Practice Problems 10

Practice Problems 10 Life Sciences 1a Practice Problems 10 1. Progesterone is a steroid hormone that prepares the body for pregnancy. Progesterone exerts its function by binding to the progesterone receptor in the cell. This

More information

AN INTRODUCTION TO IMMUNOLOGY. Paul Thomas Unit 1 Department of Immunology St. Jude Children s Research Hospital

AN INTRODUCTION TO IMMUNOLOGY. Paul Thomas Unit 1 Department of Immunology St. Jude Children s Research Hospital AN INTRODUCTION TO IMMUNOLOGY Paul Thomas Unit 1 Department of Immunology St. Jude Children s Research Hospital CATEGORIES OF PATHOGENS Viruses (~0.2 microns) Bacteria (1-2 microns) Parasites (Millimeters)

More information

Bioinformatics. Viruses, etc

Bioinformatics. Viruses, etc Bioinformatics, etc David Gilbert Bioinformatics Research Centre www.brc.dcs.gla.ac.uk Department of Computing Science, University of Glasgow Incorporating notes by Ali Al-Shahib, David Leader, and Wikipaedia

More information

ANS: Sugars combine to form carbohydrates; amino acids combine to form proteins. FEEDBACK: 2.1 DIFFICULTY: medium

ANS: Sugars combine to form carbohydrates; amino acids combine to form proteins. FEEDBACK: 2.1 DIFFICULTY: medium Solutions to Problems in Chapter 2 My comments/additions/corrections are in BOLDFACE. 2.1 Carbohydrates and proteins are linear polymers. What types of molecules combine to form these polymers? ANS: Sugars

More information

Given these characteristics of life, which of the following objects is considered a living organism? W. X. Y. Z.

Given these characteristics of life, which of the following objects is considered a living organism? W. X. Y. Z. Cell Structure and Organization 1. All living things must possess certain characteristics. They are all composed of one or more cells. They can grow, reproduce, and pass their genes on to their offspring.

More information

Liver Disease and Therapy of Hepatitis B Virus Infections

Liver Disease and Therapy of Hepatitis B Virus Infections Liver Disease and Therapy of Hepatitis B Virus Infections University of Adelaide Catherine Scougall Arend Grosse Huey-Chi Low Allison Jilbert Fox Chase Cancer Center Chunxiao Xu Carol Aldrich Sam Litwin

More information

Identification of the androgen receptor aggregates that cause spinal-bulbar muscular atrophy

Identification of the androgen receptor aggregates that cause spinal-bulbar muscular atrophy Identification of the androgen receptor aggregates that cause spinal-bulbar muscular atrophy Dr Xavier Salvatella Giralt CSIC Consell Superior d'investigacions Científiques Institut Recerca Biomèdica de

More information

Overview of Viruses. Dr. Angela M. Shaw Assistant Professor of Food Science and Human Nutrition Food Safety Extension and Outreach Specialist

Overview of Viruses. Dr. Angela M. Shaw Assistant Professor of Food Science and Human Nutrition Food Safety Extension and Outreach Specialist Overview of Viruses Dr. Angela M. Shaw Assistant Professor of Food Science and Human Nutrition Food Safety Extension and Outreach Specialist Viruses Dmitri Iwanowski - 1892 Experiments with tobacco plants

More information

Basic Characteristics of Cells. Cell Structure and Function. Each Cell Has Three Primary Regions. Basic Characteristics of Cells. The Plasma Membrane

Basic Characteristics of Cells. Cell Structure and Function. Each Cell Has Three Primary Regions. Basic Characteristics of Cells. The Plasma Membrane Basic Characteristics of Cells Cell Structure and Function Chapter 3 Smallest living subdivision of the human body Diverse in structure and function Small Basic Characteristics of Cells Each Cell Has Three

More information

IMMUNOLOGY OF HIV INFECTION AND AIDS. Interactions between HIV and the immune system

IMMUNOLOGY OF HIV INFECTION AND AIDS. Interactions between HIV and the immune system IMMUNOLOGY OF HIV INFECTION AND AIDS Interactions between HIV and the immune system Basic Statistics United States In the U.S. in 2010, 1.1 million people were living with HIV infection. About 50,000 people

More information

Chapter 9. Biotechnology and Recombinant DNA Biotechnology and Recombinant DNA

Chapter 9. Biotechnology and Recombinant DNA Biotechnology and Recombinant DNA Chapter 9 Biotechnology and Recombinant DNA Biotechnology and Recombinant DNA Q&A Interferons are species specific, so that interferons to be used in humans must be produced in human cells. Can you think

More information

Viruses. Viral components: Capsid. Chapter 10: Viruses. Viral components: Nucleic Acid. Viral components: Envelope

Viruses. Viral components: Capsid. Chapter 10: Viruses. Viral components: Nucleic Acid. Viral components: Envelope Viruses Chapter 10: Viruses Lecture Exam #3 Wednesday, November 22 nd (This lecture WILL be on Exam #3) Dr. Amy Rogers Office Hours: MW 9-10 AM Too small to see with a light microscope Visible with electron

More information

FACULTY OF MEDICAL SCIENCE

FACULTY OF MEDICAL SCIENCE Doctor of Philosophy Program in Microbiology FACULTY OF MEDICAL SCIENCE Naresuan University 171 Doctor of Philosophy Program in Microbiology The time is critical now for graduate education and research

More information

Biotechnology and Recombinant DNA

Biotechnology and Recombinant DNA Biotechnology and Recombinant DNA Recombinant DNA procedures - an overview Biotechnology: The use of microorganisms, cells, or cell components to make a product. Foods, antibiotics, vitamins, enzymes Recombinant

More information

Antibiotic susceptibility

Antibiotic susceptibility Antibiotic susceptibility Antibiotic: natural chemicals produced by bacteria, fungi, actinomycetes, plants or animals, and either inhibits or kills other microbes and/or cells Chemotherapeutic agent: A

More information

GENOME DYNAMICS TOPIC CATEGORIES - BIOCHEMISTRY AND MOLECULAR BIOLOGY

GENOME DYNAMICS TOPIC CATEGORIES - BIOCHEMISTRY AND MOLECULAR BIOLOGY TOPIC CATEGORIES - BIOCHEMISTRY AND MOLECULAR BIOLOGY ASBMB abstracts will be judged for Thematic Best Poster Awards in Anaheim! ASBMB short talks are selected from the submitted abstracts! Submit Today!

More information

TG1050, A NOVEL IMMUNOTHERAPEUTIC TO TREAT CHRONIC HEPATITIS B, CAN CONTROL HBsAg AND PROVOKE HBsAg SEROCONVERSION IN HBV-PERSISTENT MOUSE MODELS

TG1050, A NOVEL IMMUNOTHERAPEUTIC TO TREAT CHRONIC HEPATITIS B, CAN CONTROL HBsAg AND PROVOKE HBsAg SEROCONVERSION IN HBV-PERSISTENT MOUSE MODELS TG1050, A NOVEL IMMUNOTHERAPEUTIC TO TREAT CHRONIC HEPATITIS B, CAN CONTROL HBsAg AND PROVOKE HBsAg SEROCONVERSION IN HBV-PERSISTENT MOUSE MODELS Karine Lélu 1, Alexei Evlachev 1, Roland Kratzer 1, Sarah

More information

AP Biology Essential Knowledge Student Diagnostic

AP Biology Essential Knowledge Student Diagnostic AP Biology Essential Knowledge Student Diagnostic Background The Essential Knowledge statements provided in the AP Biology Curriculum Framework are scientific claims describing phenomenon occurring in

More information

Cell Biology Questions and Learning Objectives

Cell Biology Questions and Learning Objectives Cell Biology Questions and Learning Objectives (with hypothetical learning materials that might populate the objective) The topics and central questions listed here are typical for an introductory undergraduate

More information

CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES

CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES An understanding of the distinct families of molecules present on different cells of the immune system provides the tools for distinguishing

More information

TECHNOLOGY PATENTS IN THE (CONTINUED)... 16

TECHNOLOGY PATENTS IN THE (CONTINUED)... 16 CHAPTER ONE: INTRODUCTION... 1 STUDY GOALS AND OBJECTIVES... 1 REASONS FOR DOING THIS STUDY... 1 SCOPE AND FORMAT... 1 METHODOLOGY AND INFORMATION SOURCES... 2 INTENDED AUDIENCE... 2 ANALYST CREDENTIALS...

More information

Antigenic variation in Plasmodium falciparum : Erythrocyte invasion and immune escape mechanisms

Antigenic variation in Plasmodium falciparum : Erythrocyte invasion and immune escape mechanisms Antigenic variation in Plasmodium falciparum : Erythrocyte invasion and immune escape mechanisms Introduction Why does immunity to malaria take so long to develop? The parasite s survival depends on its

More information

MCAS Biology. Review Packet

MCAS Biology. Review Packet MCAS Biology Review Packet 1 Name Class Date 1. Define organic. THE CHEMISTRY OF LIFE 2. All living things are made up of 6 essential elements: SPONCH. Name the six elements of life. S N P C O H 3. Elements

More information

Plasmid Isolation. Prepared by Latifa Aljebali Office: Building 5, 3 rd floor, 5T250

Plasmid Isolation. Prepared by Latifa Aljebali Office: Building 5, 3 rd floor, 5T250 Plasmid Isolation Prepared by Latifa Aljebali Office: Building 5, 3 rd floor, 5T250 Plasmid Plasmids are small, double strand, closed circular DNA molecules. Isolated from bacterial cells. Replicate independently

More information

7.013 Spring 2005 Problem Set 7 FRIDAY May 6th, 2005

7.013 Spring 2005 Problem Set 7 FRIDAY May 6th, 2005 MI Department of Biology 7.013: Introductory Biology - Spring 2005 Instructors: Professor Hazel Sive, Professor yler Jacks, Dr. Claudette Gardel Question 1 7.013 Spring 2005 Problem Set 7 RIDAY May 6th,

More information

(ii) They are smaller than bacteria, and this can pass through bacteriological filter.

(ii) They are smaller than bacteria, and this can pass through bacteriological filter. Viruses Definition: Obligate intracellular parasite composed of: Nucleic acid - either DNA or RNA & Protein coat. Characteristics of viruses Viruses are the most primitive cellular and non-cytoplasmic

More information

Biotechnology in Medicine and Agriculture

Biotechnology in Medicine and Agriculture Biotechnology in Medicine and Agriculture Bởi: OpenStaxCollege It is easy to see how biotechnology can be used for medicinal purposes. Knowledge of the genetic makeup of our species, the genetic basis

More information

Tuberculosis and HIV/AIDS Co-Infection: Epidemiology and Public Health Challenges

Tuberculosis and HIV/AIDS Co-Infection: Epidemiology and Public Health Challenges Tuberculosis and HIV/AIDS Co-Infection: Epidemiology and Public Health Challenges John B. Kaneene, DVM, MPH, PhD University Distinguished Professor of Epidemiology Director, Center for Comparative Epidemiology

More information

The correct answer is b DNA and protein B. Answer b is correct. When DNA binds with histone proteins it forms chromatin.

The correct answer is b DNA and protein B. Answer b is correct. When DNA binds with histone proteins it forms chromatin. 1. Which of the following is NOT involved in binary fission in prokaryotes? a. Replication of DNA b. Elongation of the cell c. Separation of daughter cells by septum formation d. Assembly of the nuclear

More information

Replication of viruses An overview

Replication of viruses An overview Lec. 2 أ.د.فائزة عبذ اهلل مخلص Replication of viruses An overview Aim: Study the general steps in viral replication cycles. Objectives: 1. Viral growth curve 2. Stepwise description of specific events

More information

Genetics Lecture Notes 7.03 2005. Lectures 1 2

Genetics Lecture Notes 7.03 2005. Lectures 1 2 Genetics Lecture Notes 7.03 2005 Lectures 1 2 Lecture 1 We will begin this course with the question: What is a gene? This question will take us four lectures to answer because there are actually several

More information

Viral Replication. Viral Replication: Basic Concepts

Viral Replication. Viral Replication: Basic Concepts Viral Replication Scott M. Hammer, M.D. Viral Replication: Basic Concepts Viruses are obligate intracellular parasites Viruses carry their genome (RNA or DNA) and sometimes functional proteins required

More information

Name Date Period. 2. When a molecule of double-stranded DNA undergoes replication, it results in

Name Date Period. 2. When a molecule of double-stranded DNA undergoes replication, it results in DNA, RNA, Protein Synthesis Keystone 1. During the process shown above, the two strands of one DNA molecule are unwound. Then, DNA polymerases add complementary nucleotides to each strand which results

More information

VIRAL STRUCTURE. Nucleic acid: Either DNA or RNA Single-stranded or double-stranded Linear or circular Segmented or non-segmented

VIRAL STRUCTURE. Nucleic acid: Either DNA or RNA Single-stranded or double-stranded Linear or circular Segmented or non-segmented VIRUSES non-cellular, obligately intracellular parasites replicate not by division characteristic intracellular life cycle (eclipse period) infectious genetic information VIRAL STRUCTURE Nucleic acid:

More information

Cystic Fibrosis Webquest Sarah Follenweider, The English High School 2009 Summer Research Internship Program

Cystic Fibrosis Webquest Sarah Follenweider, The English High School 2009 Summer Research Internship Program Cystic Fibrosis Webquest Sarah Follenweider, The English High School 2009 Summer Research Internship Program Introduction: Cystic fibrosis (CF) is an inherited chronic disease that affects the lungs and

More information

1 Mutation and Genetic Change

1 Mutation and Genetic Change CHAPTER 14 1 Mutation and Genetic Change SECTION Genes in Action KEY IDEAS As you read this section, keep these questions in mind: What is the origin of genetic differences among organisms? What kinds

More information

CONTENT. Chapter 1 Review of Literature. List of figures. List of tables

CONTENT. Chapter 1 Review of Literature. List of figures. List of tables Abstract Abbreviations List of figures CONTENT I-VI VII-VIII IX-XII List of tables XIII Chapter 1 Review of Literature 1. Vaccination against intracellular pathogens 1-34 1.1 Role of different immune responses

More information

Hepatitis C Monitoring and Complications (and Treatment!) Dr Mark Douglas

Hepatitis C Monitoring and Complications (and Treatment!) Dr Mark Douglas Hepatitis C Monitoring and Complications (and Treatment!) Dr Mark Douglas Hepatitis C Virus Shimizu et al., 1996 Positive single strand RNA virus Flaviviridae family, Hepacivirus genus 9.6 kbp genome ~3000

More information

Regulation of Gene Expression

Regulation of Gene Expression Chapter 18 Regulation of Gene Expression PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from

More information

Lecture Series 7. From DNA to Protein. Genotype to Phenotype. Reading Assignments. A. Genes and the Synthesis of Polypeptides

Lecture Series 7. From DNA to Protein. Genotype to Phenotype. Reading Assignments. A. Genes and the Synthesis of Polypeptides Lecture Series 7 From DNA to Protein: Genotype to Phenotype Reading Assignments Read Chapter 7 From DNA to Protein A. Genes and the Synthesis of Polypeptides Genes are made up of DNA and are expressed

More information

CHAPTER 8 RECOMBINANT DNA and GENETIC ENGINEERING

CHAPTER 8 RECOMBINANT DNA and GENETIC ENGINEERING CHAPTER 8 RECOMBINANT DNA and GENETIC ENGINEERING Questions to be addressed: How are recombinant DNA molecules generated in vitro? How is recombinant DNA amplified? What analytical techniques are used

More information

Compartmentalization of the Cell. Objectives. Recommended Reading. Professor Alfred Cuschieri. Department of Anatomy University of Malta

Compartmentalization of the Cell. Objectives. Recommended Reading. Professor Alfred Cuschieri. Department of Anatomy University of Malta Compartmentalization of the Cell Professor Alfred Cuschieri Department of Anatomy University of Malta Objectives By the end of this session the student should be able to: 1. Identify the different organelles

More information

How Cancer Begins???????? Chithra Manikandan Nov 2009

How Cancer Begins???????? Chithra Manikandan Nov 2009 Cancer Cancer is one of the most common diseases in the developed world: 1 in 4 deaths are due to cancer 1 in 17 deaths are due to lung cancer Lung cancer is the most common cancer in men Breast cancer

More information

CHAPTER 6: RECOMBINANT DNA TECHNOLOGY YEAR III PHARM.D DR. V. CHITRA

CHAPTER 6: RECOMBINANT DNA TECHNOLOGY YEAR III PHARM.D DR. V. CHITRA CHAPTER 6: RECOMBINANT DNA TECHNOLOGY YEAR III PHARM.D DR. V. CHITRA INTRODUCTION DNA : DNA is deoxyribose nucleic acid. It is made up of a base consisting of sugar, phosphate and one nitrogen base.the

More information

Quick Hit Activity Using UIL Science Contests For Formative and Summative Assessments of Pre-AP and AP Biology Students

Quick Hit Activity Using UIL Science Contests For Formative and Summative Assessments of Pre-AP and AP Biology Students Quick Hit Activity Using UIL Science Contests For Formative and Summative Assessments of Pre-AP and AP Biology Students Activity Title: Quick Hit Goal of Activity: To perform formative and summative assessments

More information

Natalia Taborda Vanegas. Doc. Sci. Student Immunovirology Group Universidad de Antioquia

Natalia Taborda Vanegas. Doc. Sci. Student Immunovirology Group Universidad de Antioquia Pathogenesis of Dengue Natalia Taborda Vanegas Doc. Sci. Student Immunovirology Group Universidad de Antioquia Infection process Epidermis keratinocytes Dermis Archives of Medical Research 36 (2005) 425

More information

Aetiology and Pathology of Periodontal Disease. Dr. Wendy Turner

Aetiology and Pathology of Periodontal Disease. Dr. Wendy Turner Aetiology and Pathology of Periodontal Disease Dr. Wendy Turner Lecture Outline Periodontal structures and the inflammatory response Periodontal disease progression stages Pathogenesis and the host response

More information

BCOR 011, Exam 3. Multiple Choice: Select the best possible answer. Name KEY Section

BCOR 011, Exam 3. Multiple Choice: Select the best possible answer. Name KEY Section BCOR 011, Exam 3 Name KEY Section Multiple Choice: Select the best possible answer. 1. A parent cell divides to form two genetically identical daughter cells in the nuclear process of mitosis. For mitosis

More information

Chikungunya: An emerging outbreak from East Africa to Indian Ocean, 2004-2007

Chikungunya: An emerging outbreak from East Africa to Indian Ocean, 2004-2007 Chikungunya: An emerging outbreak from East Africa to Indian Ocean, 2004-2007 A. Flahault, G. Aumont, V Boisson, X de Lamballerie, F. Favier, B.A. Gaüzère, D. Fontenille, S. Journeaux, V. Lotteau, C. Paupy,

More information

Benefits in oncology. Mechanism of action

Benefits in oncology. Mechanism of action Mechanism of action The word cancer refers to a number of different diseases that share a common trait: the rapid, unrestrained growth and spread of cells that can invade and destroy surrounding tissues,

More information

General presentation

General presentation Cantacuzino National Institute of Research-Development for Microbiology and Immunology General presentation Cantacuzino National Institute of Research-Development for Microbiology and Immunology (NIRDMIC)

More information

Notch 1 -dependent regulation of cell fate in colorectal cancer

Notch 1 -dependent regulation of cell fate in colorectal cancer Notch 1 -dependent regulation of cell fate in colorectal cancer Referees: PD Dr. Tobias Dick Prof. Dr. Wilfried Roth http://d-nb.info/1057851272 CONTENTS Summary 1 Zusammenfassung 2 1 INTRODUCTION 3 1.1

More information

ATIP Avenir Program 2014. Applicant s guide

ATIP Avenir Program 2014. Applicant s guide ATIP Avenir Program 2014 Applicant s guide Important dates: - November 29 th 2013: deadline for the online submission, the mailing of the hard copy of the scientific project, and the letters of recommendation

More information

MB3001 Medical Microbiology (5 credits; Teaching Period 2A) MB3006 Genetic Engineering and Molecular Biotechnology

MB3001 Medical Microbiology (5 credits; Teaching Period 2A) MB3006 Genetic Engineering and Molecular Biotechnology MICROBIOLOGY Spring Semester 2013/2014 academic year Timetables can be accessed at http://timetable.ucc.ie/1314/department.asp Click on Microbiology For information on building codes click on: http://timetable.ucc.ie/1314/buildingcodes.asp

More information

Milestones of bacterial genetic research:

Milestones of bacterial genetic research: Milestones of bacterial genetic research: 1944 Avery's pneumococcal transformation experiment shows that DNA is the hereditary material 1946 Lederberg & Tatum describes bacterial conjugation using biochemical

More information

VIRUSES AND CANCER. Michael Lea

VIRUSES AND CANCER. Michael Lea VIRUSES AND CANCER 2012 Michael Lea VIRAL ONCOLOGY - LECTURE OUTLINE 1. Historical Review 2. Viruses Associated with Cancer 3. RNA Tumor Viruses 4. DNA Tumor Viruses HISTORICAL REVIEW Historical Review

More information

Human Immunity. How our body s cells defend against microbial and viral invaders

Human Immunity. How our body s cells defend against microbial and viral invaders Human Immunity How our body s cells defend against microbial and viral invaders What is Immunity? The word immunity comes from the Latin immunus meaning free of burden. Thus; it is a body s general ability

More information

1) Siderophores are bacterial proteins that compete with animal A) Antibodies. B) Red blood cells. C) Transferrin. D) White blood cells. E) Receptors.

1) Siderophores are bacterial proteins that compete with animal A) Antibodies. B) Red blood cells. C) Transferrin. D) White blood cells. E) Receptors. Prof. Lester s BIOL 210 Practice Exam 4 (There is no answer key. Please do not email or ask me for answers.) Chapters 15, 16, 17, 19, HIV/AIDS, TB, Quorum Sensing 1) Siderophores are bacterial proteins

More information

Cell Communication & Regulation of the Cell Cycle

Cell Communication & Regulation of the Cell Cycle Cell Communication & Regulation of the Cell Cycle 1 Why do cells need to respond to signals? 1. Need to respond to a changing environment Adaptation or a cellular response is critical for survival Glucose

More information

The role of IBV proteins in protection: cellular immune responses. COST meeting WG2 + WG3 Budapest, Hungary, 2015

The role of IBV proteins in protection: cellular immune responses. COST meeting WG2 + WG3 Budapest, Hungary, 2015 The role of IBV proteins in protection: cellular immune responses COST meeting WG2 + WG3 Budapest, Hungary, 2015 1 Presentation include: Laboratory results Literature summary Role of T cells in response

More information

Tools and Techniques. Chapter 10. Genetic Engineering. Restriction endonuclease. 1. Enzymes

Tools and Techniques. Chapter 10. Genetic Engineering. Restriction endonuclease. 1. Enzymes Chapter 10. Genetic Engineering Tools and Techniques 1. Enzymes 2. 3. Nucleic acid hybridization 4. Synthesizing DNA 5. Polymerase Chain Reaction 1 2 1. Enzymes Restriction endonuclease Ligase Reverse

More information

ELISA BIO 110 Lab 1. Immunity and Disease

ELISA BIO 110 Lab 1. Immunity and Disease ELISA BIO 110 Lab 1 Immunity and Disease Introduction The principal role of the mammalian immune response is to contain infectious disease agents. This response is mediated by several cellular and molecular

More information

Protein-responsive ribozyme switches in eukaryotic cells

Protein-responsive ribozyme switches in eukaryotic cells Protein-responsive ribozyme switches in eukaryotic cells Andrew B. Kennedy, James V. Vowles, Leo d Espaux, and Christina D. Smolke Presented by Marianne Linz and Jennifer Thornton March 11, 2015 Synthetic

More information

Gene Therapy. The use of DNA as a drug. Edited by Gavin Brooks. BPharm, PhD, MRPharmS (PP) Pharmaceutical Press

Gene Therapy. The use of DNA as a drug. Edited by Gavin Brooks. BPharm, PhD, MRPharmS (PP) Pharmaceutical Press Gene Therapy The use of DNA as a drug Edited by Gavin Brooks BPharm, PhD, MRPharmS (PP) Pharmaceutical Press Contents Preface xiii Acknowledgements xv About the editor xvi Contributors xvii An introduction

More information