Research / Scientific departments / Units and groups
Research Units and Groups
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Unit Biology of Intracellular Bacteria
Carmen BUCHRIESER Keywords: Legionella pneumophila, Legionella longbeachae, Legionella sp, genomics, biodiversity pathogenicity, virulence, gene regulation more information |
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| Topics: Legionella are environmental bacteria but some species are also opportunistic pathogens that can cause Legionnaires’ disease, a severe pneumonia, in particular in people whose immune defences are weakened. The mortality rate can reach 30%. The objective of our Unit is to identify and characterise the genetic basis of the virulence of Legionella. We aim to understand the relationship between virulence and the genetic diversity among different isolates of Legionella pneumophila and different species of Legionella, the mechanisms leading to this diversity and the role it plays in infection and environmental adaptation. In line with this, we aim to gain knowledge of how Legionella adapts/regulates its cycle between a eukaryotic host and the environment and the impact genetic diversity has in this process. We are using a genome-based approach combined with epidemiology data and comparative and functional genomics to identify new virulence factors of Legionella pneumophila and Legionella longbeachae. These factors are then studied and characterized by using molecular and cellular biology approaches as well as in vivo and infection models, in order to understand their role in intracellular infection. | |
| Fungal Biology and Pathogenicity Christophe d’ENFERT Keywords: Candida albicans, antifungals, biofilms, morphogenesis, MLST, population genetics, recombination |
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Topics : The Fungal Biology and Pathogenicity Unit using post-genomic and genetic approaches in order to investigate several aspects of the biology of Candida albicans, the main fungal pathogen of humans. Genome dynamics is studied with the aim to assess its contribution to the success of /C. albicans/ as a commensal or pathogen. We are also investigating the molecular mechanisms that underlie biofilm formation with the specific aim to understand how these microbial communities achieve an intrinsic tolerance to most antifungals. Finally, we use chemo-genetic approaches to decipher the signaling networks regulating /C. albicans /morphogenesis, a process key to /C. albicans /pathogenesis. |
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Dynamics of the Genome
Benoît ARCANGIOLI Keywords: chromosomal imprint, yeast, mating-type switch |
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| Topics: Mating type switching pattern (Kla 1990). Pattern of switching showing the asymmetric cell divisions. P, M are the mating-types and the suffix ’u’ and ’s’ represent ’unswitchable’ and ’switchable’, respectively. Schizosaccharomyces pombe cells divide by fission generating nearly equal daughter cells, thus the suffix u or s can be attributed to the dividing cell only a posteriori, when the daughter cell has expressed its mating-type. two successive asymmetric divisions are required for the first mating type switching. The pattern of switching is similar to the pattern of stem cell division in higher eucaryotes. |
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| Macromolecular Interaction Genetics Alain JACQUIER Keywords: Saccharomyces cerevisiae, RNA metabolism, non-coding RNAs, RNA maturation, RNA quality control, RNA degradation, ribosome biogenesis more information |
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| Topics:The synthesis, maturation, transport and degradation of RNA are processes that are essential for gene expression. In order to study these mechanisms, we use the yeast Saccharomyces cerevisiae as a model eukaryotic cell. We are focusing on the maturation of diverse RNAs (messenger RNA, non-coding RNAs, ribosomal RNAs), the mechanisms responsible for their quality control as well as the role played by some non-coding RNAs. | |
| Human Evolutionary Genetics (HEG) Lluis QUINTANA-MURCI Keywords: human genomics, population genetics, infectious diseases, evolutions more information |
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| Topics: Our research is focused on understanding how natural selection, human demography and lifestyle have shaped the patterns of diversity of the human genome in different populations worldwide. In particular, we are interested in exploring how infectious diseases have exerted selective pressures on human genes involved in immunity and host defence in order to unmask immunological mechanisms that have been critical for our past and present survival. To this end, our laboratory combines molecular and population genetics approaches with computational modelling, often working closely to theoretical population geneticists, immunologists, epidemiological geneticists as well as anthropologists. | |
| Physics of biological systems Massimo VERGASSOLA Keywords: Modeling; motility of biological systems; computational biology more information |
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| Topics: Our group works on quantitative modeling of biological systems by a combination of analytical and computational tools, coupled with small-scale experiments that we realize ourselves or in close collaboration with experimental groups. Recent activity was focused on computational biology of cell regulatory processes and motility of living organisms. Current and future activities of the group mostly feature projects on biological strategies of motility, namely infotaxis, bacterial and eukaryotic chemotaxis. | |
| Integrated Mycobacterial Pathogenomics Roland BROSCH Keywords: evolution; genomics; pathogenicity; mycobacteria; Mycobacterium tuberculosis; mycolactone. more information |
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Topics: The research undertaken in our unit is centered on genomics and pathogenicity of mycobacteria, to uncover novel features of mycobacterial pathogens in relation to evolution and the interaction with the host.
While most mycobacteria are harmless saprophytes, a few species have very efficiently adapted to a pathogenic lifestyle and constitute some of most important human pathogens. There are Mycobacterium tuberculosis, the causative agent of human tuberculosis, Mycobacterium leprae , the cause of leprosy and the emerging pathogen Mycobacterium ulcerans, which causes Buruli ulcer, a most serious skin disease mainly prevalent in West Africa.
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| Yeast Molecular Genetics Bernard DUJON Keywords: Comparative genomics of Hemiascomycetous ; Nuclear architecture ; chromosomal plasticity more information |
| Mycobacterial Genetics Brigitte GICQUEL Keywords: Tuberculosis, antibiotic resistance, evolution, adaptation, multidrug resistance, host-pathogen intereactions more information |
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| Topics: The Mycobacterial Genetics Unit identifies bacterial and host factors that play a role in the development of tuberculosis and protection after infection or vaccination. Approaches include: construction of attenuated mutants, analysis of host responses and use of murine models of infection. Evolution and adaptation of M. tuberculosis are studied, including adaptation towards multi-drug resistance. International TB workshops on diagnosis & detection of drug resistance are organized. | |
| Bacterial genome plasticity Didier MAZEL Keywords: integron, site-specific recombination, chromosome structure, synthetic biology, single-strand DNA, antibiotic resistance, genomic, Vibrio, horizontal gene transferdes more information |
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Topics: We are interested in the mechanisms that drive the bacterial genome variability, both in terms of gene content and physical organization, and in the specific adaptive properties brought by these mechanisms. We have two main research axes. The first is the study of the integron, a gene capture system commonly found in gram-negative bacteria, which plays an central role in the multiple antibiotic resistance development. The second is the understanding of the rules governing the organization and variability of the 2 chromosomes genomes found in all Vibrio species. |
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Systems Biology Lab
Benno SCHWIKOWSKI Keywords: Regulatory networks, network biology, computational molecular biology, algorithms, data integration, mass spectrometry, proteomics more information |
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| Topics: Our group focuses on two aspects of Systems Biology: Firstly, we develop and apply data-driven, statistical, and integrative models for cellular regulatory networks. Current projects are on the regulation of the human innate immune system, stress responses in Arabidopsis thaliana, and sporulation and competence in Bacillus subtilis. Secondly, we develop novel computational approaches for mass spectrometry-based proteomics. Here, we specialize in data integration approaches across multiple experiments. To ensure that the necessary ideas from biology and knowledge are appropriately identified and captured by our models, we work in close collaboration with experimentalist collaborators. | |
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Bacterial Evolution and Genomics
Philippe GLASER Keywords: Evolution, lateral gene transfer, transposable element, population genomics, host specificity, streptococcus |
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Topics: Our group is studying the evolution and the genomic diversity of streptococci, by focusing on two human opportunistic pathogens Streptococcus agalactiae and the Streptococcus bovis group, from macroevolution at the level of the genus to microevolution of clones during infection. Our specific objectives are (i) to characterize at the genome level the population structure of these opportunistic pathogens (ii) to define the genetic events (lateral gene transfer, deletion, insertion and duplication) leading to this diversity and to decipher the underlying molecular mechanisms (iii) to define the genetic bases of host specificity and of the commensalism to virulence transition, and (iv) to characterize the regulatory networks and their variability in the S. agalactiae population. To achieve these goals we are combining genomics, bioinformatics, molecular biology and microbiology methods and are collaborating with bioinformaticians and clinical microbiologists. |
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Evolutionary Microbial Genomics Eduardo P C ROCHA Keywords : computational biology, evolutionary ecology, microbiology, comparative genomics more information |
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| Topics: Our scientific activities are centered on the bioinformatics and biostatistics analysis of genomes, at the crossroads of molecular evolution, population genetics, evolutionary ecology and molecular genetics. We focus on three major questions: 1) How and why are genomes organized ? 2) How are such organizational features evolving in face of the extensive genome dynamics? 3) What are the roles of mobile elements in evolutionary ecology trade-offs such as between organization and dynamics or growth and adaptability? |
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| Biological Software and Databases Bernard CAUDRON Keywords: bioinformatics, biological software, databases more information |
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| Topics: The “Biological Software and Databases” group is in charge of the installation, maintenance and interfacing of biological software for the researchers. The group has added a high reliability and a user-friendly access. It gives a local access to a choice of international biological databanks useful in Genetics and Genomics. It ensures the concept of scientific databases that enable the placement of laboratory results online. Local development and deployment service is available for researchers who need bioinformatics skills to achieve their projects, or to present their results using databases and Web tools. | |
| Genomics Christiane BOUCHIER Keywords: Sequencing, Second-generation sequencing technology (Illumina Genome Analyzer IIx) more information |
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Topics:The Genomics platform (PF1) undertakes the sequencing of whole microbial genomes in collaboration with several IP teams in addition to sequencing PCR products. PF1 aims to group state-of-the-art equipment and corresponding technical and methodological process to provide for the needs of the research teams of the Institut Pasteur and its International Network in the field of sequencing projects. PF1 has a closely collaboration with the « Biological Software and Databases » Group (LBD) for installation of biological softwares and developing bioinformatic programs.
In mid 2008, the Genopole has acquired a second generation sequencing machine (Illumina Genome Analyzer IIx) which allows the production of millions of short reads in a single run. Since 2009, High-throughput sequencing approach has become a central component of the PF1 (re-sequencing microbial genomes).
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| Transcriptome and Epigenome Jean-Yves COPPÉE Keywords: Next generation sequencing, DNA microarrays, transcriptomics, epigenomics more information |
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| Topics: The DNA array platform (PF2) is dedicated to the development and use of high throughput technologies (DNA arrays and next generation sequencing) for transcriptomics (gene expression profiling, full transcriptome annotation, small RNAs sequencing...) and epigenomics studies. It is involved in projects centered on model microorganisms, pathogens, higher eukaryotes and aiming at the study of developmental biology, host-pathogen relationships and of the interactions between pathogens and their environment. | |
| Genome Analysis and integration Ivan MOSZER Keywords: BGenomics / Annotation / Integrated database / Transcriptome / Evolutionary genomics / Next-Generation Sequencing more information |
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Topics: The activities of PF4 are dedicated to data integration and analysis of large-scale genomic information, by means of software developments and collaborative projects dealing with comparative genome analysis and annotation. These activities include: assembly, annotation, and re-annotation of genome sequences, including the development of an annotation software, CAAT-Box; engineering of genomic databases, including an environment for comparative analysis of bacterial and fungal genomes, GenoList (http://genolist.pasteur.fr/GenoList), and a database for expression data, GenoScript (http://genoscript.pasteur.fr); development of tools and bioanalysis projects in evolutionary genomics; use of various genome analysis strategies, including next-generation sequencing (NGS) interpretation in population genomics studies. |
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| Space regulation of genomic functions Romain KOSZUL Keywords: chromosomal architecture ; replication ; organization ; cytoskeleton ; genome plasticity ; yeat |
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Topics: Our objectives are to contribute to the understanding of the interplay between the physical properties of chromosomes, nuclear dynamics and biological functions. Notably, the influence onto genome stability of chromosomal organization during the cell cycle. Working mostly with budding yeast, we are using routinely and developing as well post-genomic techniques (such as Hi-C derivatives), genetics, and quantitative imaging. Some of our projects are done in collaboration with physicists and mathematicians, within or outside the Institute. |
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Functional Genetics of Infectious Diseases Unit
Anavaj SAKUNTABHAI Keywords: human genetics, genetic epidemiology, functional genetics study, malaria, dengue, transmission, data mining tool, interaction study, interactomes, genome wide genetic study |
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Topics: Our unit studies the basis of human genetic susceptibility to major mosquito-borne infections, malaria and dengue. We aim not only to identify new genes governing different infection outcomes, such as disease presentation and transmissibility, but also to understand how the different alleles of these genes affect the trait. Identifying key factors underlying an outcome of interest becomes increasingly problematic as the number of variables increases and they do not work independently. We are working on creating a mathematical platform to exhaustively explore retrospective and prospective biological and epidemiological data sets and to generate hypotheses that will provide the framework for the development of predictive models of disease risk. We will learn from experimental datasets of biomolecular interactions from a cellular functional genomics model. This model allows us to integrate interactome data with genome wide genetic study
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| Eukaryote Genotyping Platform Béatrice REGNAULT Keywords: Eukaryotes, SNP genotyping, CNV, Whole-Exome Sequencing, SNV, short Indels more information |
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Topics: Addressed to the scientific community, the Eukaryote Genotyping Platform (PFGe) provides high-throughput technologies in genetics and genomics in order to discover variants responsible for phenotypic traits in human populations and diseases. Technologies are available for genotyping of bi-allelic markers such as SNPs (Single Nucleotide Polymorphisms) and for the analysis of CNV (Copy Number Variants) across the human genome-wide (Illumina Infinium) or custom genotyping for studying focused genomic regions of interest on any species (Illumina GoldenGate). The massive DNA sequencing (Illumina HiSeq 2000) is used for the discovery of SNVs (Single Nucleotide Variants) and short Indels, focused on the 1.5 % of the genome coding for proteins (Whole-Exome Sequencing) or on large targeted sequences. The platform is also involved in the development and provision of tools for data analysis. |
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