BISTRO
Beautiful Interface and System To Report and Organize
Development of a Software tool to integrate Bottomp-up, Middle-down and Top-down proteomics data
The aim of the project is to develop a powerful software tool to integrate MS data for the visualization of the protein coverage and mapping of Post Translational Modifications (PTMs). Even if some to...
Implémentation d’un algorithme rapide de génotypage cgMLST
Le génotypage MLST (Multi-Locus Sequence Typing) est une technique standard qui permet une caractérisation génotypique précise et reproductible des souches bactériennes. Elle consiste à déterminer la ...
ChIP-seq analysis of the majour regulator of GBS virulence
Streptococcus agalactiae (GBS) is a gram positive-bacteria which asymptomatically colonize the genital and intestinal tract of healthy women, although the leading cause of bacterial invasive infection...
Fusion proteins in mammals and yeasts
Membrane fusion is an essential process in all forms of life, and fusion proteins are responsible of catalysing this reaction by forcing the two membranes against each other by undergoing a fusogenic ...
Genetic traits involved in the regulation of NK cell and ILC homeostasis and NK cell-mediated anti-tumor functions
This project aims at identifying novel genetic traits that regulate the anti-tumor activities of NK cells and homeostasis of NK cells and other ILC using an unique mouse resource, the Collaborative Cross (CC). CC is a panel of recombinant inbred mice derived from randomized breeding of eight laboratory inbred strains combining high genetic diversity with the advantage of inbred mouse strains. We have identified CC strains that diverge in their anti-tumor immune responses and are characterizing ...
Defining Shigella-targeting of human lamina propria mononuclear cells using CyTOF technology
Invasion of human intestinal epithelial cells by Shigella flexneri is secondary to the delivery of bacterial effectors into the host cell cytoplasm via a type III secretion system (T3SS). By using a beta-lactamase reporter tool we observed that in contrast to the epithelium, human lymphocytes are mainly targeted by injection of T3SS effectors not resulting in subsequent cell invasion (Pinaud et al., 2017). Furthermore, we observed that the targeting process, in form of successful injection of ef...
Search for non-annotated transcripts in zebrafish lymphocytes
With collaborators in Cambridge, we performed single-cell sequencing of various types of zebrafish lymphocytes. However, standard mapping misses many interesting genes, which are not properly annotated yet in the zebrafish genome. The aim of this project would be to provide a simple way to BLAST for given sequences, from nonannotated genes, in this dataset....
Exploring immunological mechanisms of human graft-verus-host disease after hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematologic malignancies. The main therapeutic benefit derives both from the ability to treat patients with intensive chemotherapy and from a potent graft-versus-leukemia (GVL) effect mediated by donor T lymphocytes. Unfortunately, in some patients, donor T cells also attack host normal tissues, giving rise to graft-versus-host disease (GVHD). GVHD prevalence is between 40-80% depending on patient and transplantat...
MOODel: Modeling Mood Disorders
Mood disorders such as bipolar and major depressive illnesses are among the most severe psychiatric disorders. They have high prevalence and chronic course, and are associated with significant mental and somatic comorbidities and high personal and societal costs (lost productivity and increased medical expenses). Patients with bipolar disorder (BD), for example, exhibit a reduced lifespan compared with the general population, a finding that cannot only be explained by high suicide risk, reduced ...
Role of ATM in EBV latency
Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by a biallelic mutation of the Ataxia Telangiectasia Mutated (ATM) gene. The ATM protein is involved in a very large number of cellular functions (over 700 substrates), mainly DNA repair, cell cycle regulation, mitochondrial and oxidative metabolism, as well as regulation of gene expression. The majority of hematological malignancies occurring in AT patients are non-Hodgkin's B lymphomas and Hodgkin's lymphomas. The ass...
Next Generation Surveillance of Salmonella and Shigella infections
Whole genome sequencing is revolutionizing the surveillance of foodborne and waterborne bacterial pathogens. The speed with which public health laboratories obtain information after the onset of symptoms and the regular sharing of this information between public health laboratories and epidemiologists are critical for the successful use of information to detect outbreaks early and to identify their source. For this purpose, this project aims at providing the most relevant bacterial genomic infor...
Transcriptome of epithelial cells challenged with different serotypes of S. pneumoniae
The project is to identify differentially modified genes and pathways in epithelia cells when challenged with Streptococcus pneumoniae serotypes. S. pneumoniae has >90 different serotypes designated as either “carrier” or “invasive”. Some serotypes of S. pneumoniae are naturally carried within the nasopharynx (carrier), or are opportunistic serotypes that escape the nasopharynx causing disease within the host (invasive). In the case of a carrier serotype, the host is able to clear/con...
Modulation of neutrophil cytosolic proteome in GCSF-treated patients. Impact of sample treatment
Neutrophils are the most abundant immune cells circulating in the blood and recruited to infectious sites. Neutrophil survival is a critical aspect for their study in vitro. We propose to study the impact of anoxia and GCSF treatment on neutrophil cytosolic protein abundance...
Analyse statistique d'interactions protéine-protéine
Réalisation d'un interactome entre des protéines de mammifères et une protéine bactérienne de virulence....
Extracting spatiotemporal gene expression activity from live biological tissues
In early development, regulation of transcription results in precisely positioned and highly reproducible expression patterns that specify cellular identities. How transcription, a fundamentally noisy molecular process, is regulated to achieve reliable embryonic patterning remains unclear. In particular, it is unknown how gene-specific regulation mechanisms affect kinetic rates of transcription, and whether there are common, global features that govern these rates across a genetic network. Quant...
State and parameter inference for stochastic models of gene expression
Quantitatively understanding the stochastic dynamics of gene expression requires measurements at the level of single cells. A common approach to follow the expression of genes in single cells and in real time is to make use of fluorescent reporter proteins and to record the cells' fluorescence by microscopy. However, this provides only an indirect readout of the biological processes that are of interest such as the regulation mechanisms at the promoter. A possible way to uncover the unobservable...
Identification of the mouse and/or rat orthologues of the human gene ANOS1, responsible for the X-chromosome-linked form of Kallmann syndrome
The human gene ANOS1, responsible for the X-chromosome-linked form of Kallmann syndrome (a developmental disease affecting the olfactory system), has been identified in 1991 by positional cloning. It is located on the X chromosome short arm (at Xp22.3), close to the STS gene and close to the boundary of the pseudoautosomal region (common to the X and Y sex chromosomes). Since then, orthologous genes have been identified in all animal species (including invertebrates), except in the mouse, rat, a...
characterization of RNA virus populations from untargeted NGS in natural infections samples
There is a wide variation in both animal and human risk and outcome of infection, generally encompassing asymptomatic, to more severe and sometimes lethal cases. Dengue virus, a re-emerging arbovirus is a great examples of this, as it lead to a very wide spectrum of disease severity. Genetic variation associated with intrahost populations has been postulated to influence viral fitness and disease pathogenesis. This project aims to characterize the complexity of viral populations in samples fro...
Evaluation de la représentativité génétique d'un pool de souches
Objectives: Our objective was, through whole genome sequencing, to establish a comprehensive repertoire of the non-synonymous polymorphisms (natural polymorphisms and/or mutations of resistance) in genes involved in resistance to azoles and echinocandins. Methods: Two collections of C. albicans clinical isolates were used. The first one consists of 151 epidemiologically-unrelated strains susceptible to antifungal agents. The second one consists of 9 isolates resistant to fluconazole and 1 to f...
Analysis of methylation for HIV patients with co-infections
It has been shown that methylation can act as a kind of memory of the immune system. For patients with co-infections, it is of particular importance to know when to begin an anti-retroviral therapy, especially if they are already infected with tuberculosis. The goal of this study is to find hyper or hypo methylated loci related to the reaction of HIV patients (co-infected or not) to different kind of treatments....
BD-CheM - Development of a chemical database to store structural and physico-chemistry data
The purpose of this short project is to develop a database that can efficiently store millions of unique molecular compounds along with some of their already calculated properties. The database named BD-CheM should be able to deal with extensive sets of data: millions of compounds and several hundreds of molecular properties. The import of new data should deal with the detection of molecule uniqueness to prevent data redundancy and with multiple sources of molecular compounds to keep track of th...
Insight into the Immune System: A bioresource and data-sharing platform to study chronic inflammatory diseases (IsIShare)
Chronic inflammatory systemic diseases (CIDs) are a burden to humans because of life-long debilitating illness, increased mortality and high therapy costs. CIDs’ increasing prevalence in western countries has indeed placed them at the third rank of morbi-mortality causes. Unfortunately, available treatments are poorly targeted and non-curative. That is partly linked to a complex and largely ununderstood pathophysiology. Genetic susceptibility clearly plays a role. Genes linked to the immune sy...
CRC related Dysbiosis
Analyasis of environemntal factors in the occurenc eof CRC by comparing normal colonosopcy and CRC patients in two categories : sporadic (average risk) and constitutional gene mutated individuals (very high risk) for CRC...
Microbiota dysbiosis in human colon cancer
Colon cancer (CRC) is frequent, of bad prognosis, whilst the cost continues to increase. Environmental factors play a role in the majority of sporadic CRC cases. All members of a family share common environment factors and gene determinants. In about 5% of CRC, dominant role of gene is identified as Lynch Syndrome (LS) with mutation in DNA mismatch repair (MMR) genes. Considering the high lifetime risk of developing carcinomas in these individuals, it is relevant to study whether modifiable life...
Implication du plasmide pKOBEG dans le génome d'Escherechia coli 55989
Le plasmide pKOBEG est un plasmide de recombinaison classique utilisé pour faire de la mutagénèse chez les bactéries et particulièrement chez Escherichia coli. Cependant, nous avons pu constater que le plasmide lui-même engendrait des modifications au sein de la souche Escherichia coli 55989 entéroaggrégative. Afin de déterminer l'étendue des modifications du à ce plasmide dans une souche wild type, nous avons séquencé le génome de nos souches WT et en présence du plasmide ainsi q...
Physical Contact between human and non human primates in Southeastern Cameroon
Non human primates are an important reservoir for zoonotic disease. Here we analyze in Cameroon how human activities in the forest influence contact with non human primates to better understand processes of emergence....
Mechanisms of phage resistance in Vibrio cholerae O1 biotype classic
phage phiVC8 is a lytic phage for Vibrio cholerae 01 biotype classic. This phage has a narrow host range and we are interested to undersatand why. We have selected several mutants of the Vibrio strain resistant to the phage. Resistance could be due to several mechanisms that we want to uunderstand...
DNA encapsulation of human resources for research projects on immune system and inflammatory diseases
Freezing is the most commonly used method for storing DNA extracts. However, that method is non-practical and expensive, since requiring freezers and back-up generators for storage, and specific conditions/reagents for transport. In addition, even when adequate procedures are followed, the frozen extracts integrity might suffer from repeated freeze-thaw cycles or residual microorganism activity. The Institut Pasteur’s ICAReB platform hosts the biological collection related to the CoSImmGEn c...
Analysis of DNA methylation in the presence and absence of antibiotics in wt and mutant V. cholerae
The goal of this project is to study the strategies undertaken by Gram negative bacteria to respond to sub-lethal antibiotic stress. We previously established that low doses of antibiotics that do not affect bacterial growth still induce stress responses in bacteria and suggest that understanding the mechanisms underlying these stress responses can prime strategies to increase antibiotic treatment efficiency. In this project, we will address consequences of stress responses and pathways activate...
Phylogenetic analysis of HHD-PDZ containing proteins
Harmonin Homology Domains (HHD) are protein-protein interaction domains primarily identified in a few proteins involved in earing and vision. Only six HHD-containing proteins encompassing 9 HHD domains have been identified so far in mammals. Four of these proteins are neuronal and also contain PDZ domains, exhibiting different HHD-PDZ modular organisations. This project aims at 1) searching orthologs with HHD domains, 2) establishing the phylogenetic tree of HHD-containing proteins and 3) unders...
Finding and Predicting CRISPR-Cas9 Efficiency
CRISPR-Cas systems provide immunity to bacteria and archaea. One of the reasons these systems have attracted so much attention in the past few years is due to the discovery of nucleases among the Cas proteins that are guided by small RNAs to bind and degrade homologous DNA. The introduction of breaks in DNA that can be repaired either in a controlled or uncontrolled manner now is a widely used method to introduce mutations in genomes. We are interested in probing the CRISPR-Cas system efficienc...
Identification of APOBEC3 mutations in cancer genoms
The APOBEC3 proteins (APOBEC3A-H) are single-stranded DNA (ssDNA) cytidine deaminases (CDAs). Those proteins were first tied to innate immunity as antiviral restriction factors as cytidine deamination to uridine results in hypermutation of viral genomes. However APOBEC3 mutațional signature was recently identified in cancer genomes, suggesting a causal role of APOBEC3 proteins in cancer onset. Accordingly, we demonstrated that both APOBEC3A and APOEC3B proteins can elicit somatic mutations on ...
Prediction of Congenital Infection in Tunisian Pregnant Women
Congenital infections are considered to be as a public health problem. It can affect the unborn fetus and newborn infants and may cause perinatal morbidity and lifelong handicaps. They are generally caused by viruses, bacteria and/or parasites when primary infection occurs during the first months of pregnancy or through the time of delivery. Cytomegalovirus (CMV) infections are major contributors to prenatal and infant morbidity and mortality. In countries with relatively low socio-economic lev...
CNF-domain containing toxin family
Alterations of the cellular proteome over time due to spontaneous or enzymatic deamidation of glutamine (Gln) and asparagine (Asn) residues is a probable source of aging-related diseases. In particular, deamidation of a conserved glutamine in all GTPases of the Ras superfamily that are essential for cellular GTP turnover, confers to these molecular switches gain-of-function properties that can stimulate oncogenic signaling pathways. The CNF1 toxin produced by pathogenic Escherichia coli, a preva...
Impact of gut microbiota on lipid metabolism
We have shown that chronic stress impact gut microbiota and leads also to metabolomic abnormalitites . We want here to decipher whether particular gut bacterial species could be directly link to the metabolism differences we observed....
Duplications in bacteriophage genomes.
We recently reported an unusual homologous intra genomic recombination event within the the tail fiber genes of one bacteriophage and shown that is event is conserved in several other tail fiber genes from bacteriophages of the public database. Now, we aim at recording the frequency of this event and its position in the all available bacteriophages genomes....
Identification of Ago2-bound nuclear transcripts and genomic loci in adult zebrafish neural stem cells
Adult neurogenesis is the process by which adult neural stem cells (NSCs) produce new neuronal and glial cells throughout an animal life. Studies in vertebrates have unveiled the crucial importance of this phenomenon for neural tissue homeostasis and proper brain function. Fundamentally, this process is a balance between maintaining a quiescent NSC pool and recruiting them into the neurogenesis cascade. Using the adult zebrafish anterior brain (telencephalon) as a model, we aim at deciphering th...
Characterization of the role of Argonaute proteins in regulating germline gene expression at the transcriptional and the post-transcriptional levels.
This research project focuses on the characterization of the role of small RNAs and their associated Argonaute proteins in transcriptional and post-transcriptional regulation of germline gene expression. Using the nematode C. elegans, we have recently showed that one of the germline-expressed Argonaute protein, CSR-1, promotes germline transcription. However, CSR-1 also possess an endonucleolytic activity that might participate in post-transcriptional silencing. Therefore, two possible functions...
Mapping of Enhancers from transcriptome data
Enhancers of transcription are regulatory sequences enabling gene expression from a distance. The landscape of active enhancers is cell-type specific and provides extensive information on the transcription factors at play. Currently, enhancers are mostly mapped based on the histone modifications positioned on their DNA sequence. This type of data is abundantly available for tumor-derived tissue culture cells, but difficult to obtain when the biological material has a limited availability. As an ...
Analysis of IFITM RNA levels in vraious cell types and tissues
The interferon-induced transmembrane (IFITM) proteins protect cells from diverse virus infections, including Influenza, HIV and Zika viruses, by inhibiting virus-cell fusion. We showed that IFITM proteins act additively in both productively infected cells and uninfected target cells to inhibit HIV-1 spread, potentially conferring these proteins with greater breadth and potency against enveloped viruses. We also reported that amino-terminal mutants of IFITM3 preventing ubiquitination or endocytos...
Evolutionary approach to protein thermal stability
Phylogenetic analysis of protein families to find mutations that increase their thermal stability and expression levels in a cost- and labor-effective way....
VCF filtering script
A partir de fichier VCF appliquer un certain nombre de filtre et retourner un fichier VCF...
Genomic determinants for initiation and length of natural antisense transcripts in a compact eukaryotic genome and phylogenetic analysis of related Entamoeba species
Entamoeba histolytica is a protozoan parasite and an amitochondriate pathogenic amoeba, which causes amoebiasis (dysentery and liver abscess) in humans. In addition to E. histolytica several species infect the human intestine although these do not cause disease and include in most of cases E. dispar and ocassionnally E. moshkovskii. A phylogenetically close Entamoeba, E. invadens infecting snails, is used as cellular model for Entamoeba cyst formation.
Supported by the National Agenc...
- Non coding RNA
- Phylogenetics
- RNA-seq + 2 keywords
Channels in metagenomics data
We would like to have a detailed picture of the presence (or not) of several types of ion channels in some metagenomic data....
Phylogenetic analysis of insect-specific flaviviruses
Mosquitoes are vectors for flaviviruses such as dengue virus or Zika virus that cause a substantial public health burden worldwide. These vectors are also infected with insect-specific flaviviruses that can only replicate in mosquitoes and are unable to replicate in cells of vertebrate organisms, such as humans. Many of them were discovered and sequenced in the last few decades. Despite several studies on their phylogenetic analysis to date, the analysis should be regularly updated. Therefore,...
Characterization of a Salmonella mutant carrying a single amino-acid substitution in the stress sigma factor RpoS
The RpoS/σS sigma subunit of RNA polymerase is the master regulator of the general stress response in many Gram-negative bacteria. σS also contributes to virulence and biofilm formation of the human pathogen Salmonella enterica serovar Typhimurium. We have used RNA-sequencing to unravel the σS-dependent transcriptome in S. Typhimurium ATCC14028. These studies have revealed a major effect of σS on the remodelling of metabolism and membrane functions, and have highlighted the importance of d...
Genotype to phenotype analysis of immune responses in chronic inflammatory diseases
Chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, spondyloarthritis (SpA) and psoriasis cause significant morbidity and are a substantial burden for the affected individuals and the society. An important obstacle to early diagnosis and the development of more specific and effective therapies is the very limited understanding of the pathogenesis of these diseases. In the past years genome-wide association studies have identified many genes that were not known...
The resurgence of a neglected disease, Yellow fever: from jungle to urban environments
Yellow fever virus (YFV), a Flavivirus transmitted by mosquitoes causes a severe hemorrhagic fever in humans. Despite the availability of a safe and effective vaccine (17D), YFV is still a public health problem in tropical Africa and South America. In the Americas, the massive campaign of mosquito control during the first half of the 20th century led to the eradication of Aedes aegypti from most American countries, and as a consequence, urban outbreaks of YF were no longer observed. However, the...
Environmental and human surveillance of polioviruses, VDPVs, and other enteroviruses in Madagascar and the impact during the switch from tOPV to bOPV
Poliomyelitis has been a major public health concern and currently, efforts are being made towards eradicating wild poliovirus type 2 (WPV2). A global switch from trivalent oral poliovirus vaccine (tOPV) to bivalent oral poliovirus vaccine (bOPV without PV2) has taken place in countries, like Madagascar, where epidemics of recombinant type 2 pathogenic circulating vaccine-derived polioviruses (cVDPVs) were reported in the last decade. This occurs when low polio vaccine coverage and high populati...
Amélioration des techniques permettant la détection de poliovirus dans l'environnement.
Les poliovirus sont les agents étiologiques de la poliomyélite, une maladie qui fait l’objet d’un programme mondial d’éradication conduit par l’OMS dans lequel sont impliqués l’Institut Pasteur de Paris et de nombreux laboratoires du réseau international des instituts Pasteur. Les poliovirus se répliquent principalement dans l’intestin des sujets infectés et sont excrétés dans les selles. Ils peuvent ainsi être retrouvés dans des échantillons d’eaux usées. La surveil...
Détection et assemblage d’entérovirus dans des échantillons cliniques et environnementaux
PARTIE 1: Résolution des problèmes liés à l’assemblage de novo de génomes recombinants présents sous forme de mélanges dans les échantillons cliniques et environnementaux La recombinaison génétique est un phénomène très fréquent chez les entérovirus. Celle-ci consiste en la génération de génomes chimériques constitués par l’assemblage de séquences génétiques provenant de différents génomes parentaux. La présence dans des échantillons cliniques ou environementaux...
De novo sequencing and analysis of three unassigned species of non tuberculous mycobacteria.
In recent years, the number of non-tuberculous mycobacteria (NTM) isolated from clinical specimens has increased greatly, due to opportunistic infections accompanying immunosuppression, but also as a result of improved culture and identification techniques. It becomes increasingly clear that NTM, or at least some of them, might be responsible for difficult-to-treat infections in immunocompetent hosts. In this respect, we have undertaken a study aimed at characterizing NTM that were isolated f...
viral evolution around Ebola Treatment Center in Macenta
Samples were collected in the field from infected patients admited in Ebola treatment Center of Macenta (ETC Guinea). Deep sequencing was performed in order to look for majority and minority variants. The aim of this study is to compare quasispecies of patients who survived and those who died and also to get detailed description of EBOV evolution in an ETC to identify phylogenetic clusters or transmission chain....
identification of sRNA in Leptospira biflexa and influence of a putative Hfq on the transcriptome
In a previous project (collaboration with PF2 and C3BI) , we determined the transcriptome landscape of the pathogen Leptospira interrogans (Zhukova A, Fernandes LG, Hugon P, Pappas CJ, Sismeiro O, Coppée JY, Becavin C, Malabat C, Eshghi A, Zhang JJ, Yang FX, Picardeau M. Genome-Wide Transcriptional Start Site Mapping and sRNA Identification in the Pathogen Leptospira interrogans.Front Cell Infect Microbiol. 2017 Jan 19;7:10.). In the present project, we performed RNA-seq with the PF2 on the sa...
AIMyc: Analysis of the Impact of antibiotics, antifungals on the Mycobiome of allogeneic stem cell recipients.
Patients undergoing hematopoietic stem cell transplant (HSCT) are known to be at risk of invasive candidiasis despite antifungal prophylaxis with Candida dissemination occurring from the gut mycobiome to the bloodstream. These patients are given antifungal drugs, antibiotics known to impact growth and favor the selection of some intrinsically resistant fungal species. The AIMyc project proposes to depict the impact of antifungal, antibiotics treatments on the diversity of species within the myc...
Trichosporon asahii NGS analysis
Trichosporon asahii is a yeast responsible of human invasive infection worldwide. Actually, no genotyping method is available to determine relationship between clinical isolates. At the NRCMA we have more than 40 clinical isolates and 2 collection strains associated with clinical data. Thanks to P2M facility, whole genome for 33 isolates was sequenced. The aim of this project is to study the genetic diversity of Trichosporon asahii and the potential relationship with clinical and/or phenotypic d...
Assembly of insect virus genome
Mosquitoes of the Anopheles gambiae complex display strong preference for human blood- meals and are major malaria vectors in Africa. However, their interaction with viruses or role in arbovirus transmission during epidemics has been little examined, with the exception of O’nyong-nyong virus, closely related to Chikungunya virus. We have recently identified two novel insect RNA viruses, a Dicistrovirus and a Cypovirus, found in laboratory colonies of An. gambiae taxa using small-RNA deep seq...
Effects of expanded-spectrum cephalosporins ( ceftriaxone or céfotaxime) on the human gut Mycobiome
The gastrointestinal tract of humans is colonized by hundreds of microbial species, - bacteria, archaebacterial, fungi, protozoa and viruses -, collectively named the gut microbiome. The intestinal commensal bacteria have an important role in metabolic processes and contribute to colonization resistance against intestinal pathogens. Fungi are usually considered to be a minor component of the global microbiome. However, the mycobiome (fungal component of the entire microbiome) has been in fact l...
Characterizaion of the microbiome of lab colonies of Aedes aegypti
The goal of the project is to determine if there are differences in the midgut microbiome of our lab colonies of Aedes aegypti. We frequently observe various phenotypic differences between different colonies of mosquitoes and it is a recurring question whether these phenotypic differences are a result of differences in the microbiome. We will sequence the microbiome of 6 representative established lab colonies that have been collected from geographically diverse areas and compare the bacterial ...
Super-resolution imaging and reconstructions of human cell chromosome architecture
Chromosomes are arranged non-randomly in the 3D space of cellular nuclei. This architecture is important to key biological processes including gene expression and DNA repair, but remains poorly understood in detail. Genome-wide chromosome conformation capture (Hi-C) is currently the most powerful experimental technique to probe chromosomal structures. However, this technique does not directly provide a description of high-resolution chromosomal configurations in individual cells and remains blin...
Functional interactions between HP1 proteins and RNA.
The three HP1 proteins (Heterochromatin Protein 1 alpha, -beta, -gamma) are epigenetic markers of heterochromatin, the condensed, repressed form of chromatin. They are typically known to associate to the di-/tri-methylated lysine 9 of histone H3 (H3-K9me2/3), a repressive histone mark, HP1s are therefore linked to chromatin silencing. But on the other hand, HP1s are also linked to activated transcription, for example HP1g has been shown to localize within the body of coding genes in correlation ...
Biomarqueurs d’identification précoce du sepsis aux urgences (BIPS)
Rationnel. Le mode de présentation clinique du sepsis est très polymorphe. Chez les patients septiques consultants dans les services des urgences, la présence d’une hyperthermie ou d’autres critères du syndrome de réponse inflammatoire systémique (SIRS) n’est pas suffisante pour aider au diagnostic de sepsis. De nombreux efforts de recherche ont abouti à la proposition d’innombrables biomarqueurs de sepsis essentiellement étudiés en soins intensifs. Même si cer...
Multi-traits GWAS in Malaria
Malaria is a complex disease resulting in more than 700,000 deaths per year, most notably among under 5-year olds in sub–Saharan Africa. Malaria is caused by several Plasmodium spp. parasites of which P. falciparum is responsible for the majority of deaths worldwide. Parasites are inoculated by infectious mosquitoes during their bloodmeal. Subsequent development of the parasite within the liver leads to the blood stage infection, where parasites replicate within red blood cells leadin...
the role of host defense in female genital tract infection by Chlamydia trachomatis
The present work is to systematically investigate the role of TLRs and NODs in the host defense during C. trachomatis infection using KO animals. The inflammatory cytokines and bacterial burden will be measured using Bio-Plex ELISA kit. C3BI will provide help in the data analysis....
Comparing V-J gene usage for specific antibody generation
Notre but est de trouver un test statistique capable de dire si deux matrices de nombres sont différents. Ces matrices correspondent à l’utilisation de fragments de gènes (V ou J) pour créer un gène ré-arrangé (V-J) codant pour un anticorps de spécificité particulière. Ici nous avons représenté pour chaque gène V la famille de gène J utilisé (parmi J1, J2, J3, J4). Le nombre correspondant au nombre d’occurrences que nous avons trouvé après séquençage du répertoire d’ant...
Relationships between ESBL-producing Escherichia coli from food and healthy mothers in Phnom Penh, Cambodia
Extended spectrum β-lactamase (ESBL) genes encode resistance to penicillins and cephalosporins and can be horizontally transferred among Enterobacteriaceae. More than 60% of healthy humans living in southeast Asia are faecal carriers of ESBL-producing Enterobacteriaceae (ESBL-PE), compared to <10% in Western Europe, suggesting diverse exposure routes. In Cambodia, meat and fish consumption is high and food safety is poorly enforced. Thus, we hypothesized that meat and fish ...
NOXO1 interacting partners in intestinal epithelial cells under inflammatory and infectious conditions
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (or NOX) are a unique family of enzymes dedicated to the production of reactive oxygen species (ROS) such as superoxide anion (O.-2) and hydrogen peroxide (H2O2) (1). This family includes NOX1-5, DUOX1 and DUOX2 and has been defined on the basis of its members’ structural homology with gp91PHOX (now renamed NOX2), the catalytic core of the phagocyte NADP...
Investigating developmental defects of a C. trachomatis mutant strain
Invasion of epithelial cells by the obligate intracellular bacterium Chlamydia trachomatis results in its enclosure inside a membrane-bound compartment termed an inclusion. The bacterium quickly begins manipulating interactions between host intracellular trafficking and the inclusion interface, diverging from the endocytic pathway and escaping lysosomal fusion. We have isolated a mutant strain that shows several developmental defects. The C3BI will contribute to the statistical analys...
Heritability of the melatonin synthesis pathway in Autism Spectrum Disorders
Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with a complex genetic architecture. They are characterized by impaired social communication, stereotyped behaviors and restricted interests and are frequently associated with comorbidities such as intellectual disability, epilepsy and severe sleep disorders. Hyperserotonemia and low melatonin levels are among the most replicated endophenotypes reported in ASD, but the genetic causes of such alterations remain largely...
Transcriptional profile of Nod2+ neurons upon MDP signaling
I am interested in gut-brain axis and specifically how a bacterial metabolite, MDP, can be sensed directly by neurons....
Assess possible correlations between enteric viruses found in sewage waste water and healthy Roma children in Romania in the period 2016-2017
Enteroviruses are among the most common viruses infecting humans and can cause diverse clinical syndromes ranging from minor febrile illness to severe and potentially fatal diseases. Among them, polioviruses (PVs) are the etiologic agent of paralytic poliomyelitis, a disease characterised by acute flaccid paralysis due to the destruction of motor neurons following PV replication. Thanks to the high coverage rate within the different contries, the WHO European region was certified polio-free m...
Analyse génomique de corynebacterie
Vérification et cartographie de génomes de corynebacteries modifiés. Recherche de suppresseurs à partir de délétions de gènes de kinase (pknA; pknB ...)...
Infection of Ixodes ricinus by Borrelia burgdorferi sensu lato by in peri-urban forests of France
Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. In Europe, it is transmitted by Ixodes ticks that carries bacteria belonging to the Borrelia burgdorferi sensu lato complex. Our study was focused on peri-urban forests of Île-de-France. These forests are frequented by many visitors and the risk of exposure to tick bites is high. One of them, the Sénart forest, is located 30 km south of Paris (in the Île-de-France region) and has a large numbe...
Experimental evolution of Chikungunya and Zika viruses’ strains to study emerging variants.
Chikungunya and Zika viruses have recently extended to previously disease free areas. In addition, their high mutations rates and fast replication lead to the emergence of new strains potentially able to disseminate in these new territories, through the apparition of novel characteristics. The African (MR-766) and American (PRVABC-59) Zika strains, and the La Reunion Island and Caribbean Chikungunya strains, were passaged several times in mammalian or mosquito cells only or alternatively in o...
Salmonella CRISPR database
CRISPR polymorphism is a powerful tool to subtype Salmonella strains and is now used in routine for epidemiological investigations. The aim of this project is to transfer and upgrade a published and worldwide used webtool to extract the spacer content from fasta sequences or paired-end reads....
Metabolic characterization of ILCs under homeostatic or stress conditions
Innate lymphoid cells (ILCs) are the most recently identified components of the innate immune system. ILCs colonize different tissue sites and react promptly to microenvironmental perturbations. Due to their high plasticity, ILCs can shape their functional output in response to local cues. As such, ILCs play roles under homeostatic conditions and in the context of infection, chronic inflammation, metabolic diseases and cancer. Diverse ILC subsets (NK cells, ILC2) have been shown to regulate...
Common and phylogenetically widespread coding for peptides by bacterial small RNAs – Follow up of a project regarding its journal review
Following a collaboration started a few years ago between a postdoc of the System Biology team (Robin Friedman) and Olivia Doppelt-Azeroual, a publication is in review in the journal Genome Biology. One of the reviewers made comments regarding the database and web interface implemented by Olivia at the time and after a brainstorm on the review, the first author (Robin) needs to make a few modifications on the database. This modification requires Olivia's intervention to update the database a...
Performing Gene Ontology Analysis on RNAseq data in Aedes aegypti
Our team studies interactions between arboviruses and Aedes aegypti mosquitoes. We recently generated RNAseq data to analyse the response of the mosquito to virus infection. We would now like to analyse that data using Gene Ontology to find pathways or processes that are activated upon infection....
INNOV DIAG HPV VALOEXPRESS
Molecular markers of cervix lesions linked to HPV infections....
Looking for the SNPs in evolved Corynebacterium diphtheriae genomes
Searching and annotating SNPs in evolved Corynebacterium diphtheriae genomes...
TB drugs and host response
Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (MTB), is the deadliest disease due to a single infectious agent. Despite considerable efforts to fight the disease, TB remains a major public health problem. Even more worrying for the future, multidrug resistant (MDR) strains of MTB are continually emerging and about 10% of people with MDR-TB have extensively drug-resistant TB (XDR-TB). Drug-sensitive TB can be cured by a 6-month treatment using 4 antibiotics, but MDR-TB...
Evaluation of the GO annotation of the Leishmania donovani genome
We are generating massive amounts of omics data for Leishmania donovani. Anna Zukhova enabled to use the BiNGO module of Cytoskape to perform and visualize our GO enrichment analyses. We would like to continue our collaboration and ask Anna's help to assess the current state of GO annotation of the Leishmania genome and if possible to complete it using domain searches or ortholog mapping from other genomes, including L. major, T. bruce or model organisms such as yeast. We expect that improveme...
Transcriptomic analysis of blood cells from ebola infected patients
Blood cells were collected in the field from patients admited in the Ebola treatment center of Macenta (Guinea). After red cells lysis, blood cells were frozen and RNA was extracted after the shipment of samples in France. Despite poor RNA quality, Affimetrix chips have been performed and transcriptomic data are available. The aim of this study is to compare the transcriptomic data from patients who survived and those who died and also to perform a kinetic analysis of the infection in the two gr...
Genomic analysis of catheter-related Escherichia coli infection
Escherichia coli is one of the major bacterial pathogens that are responsible for numerous nosocomial infections. While most of the E. coli infections are rather related to colonisation of the urinary...
Lipid-binding domains in Vaccinia virus proteins
Our lab is interested in the assembly of the inner viral membrane of Vaccinia virus and what are the molecular regulators (proteins and lipids) playing a role in this complex and unique process of virion morphogenesis....
Histone Methyltransferase and Demethylase in Leishmania
I would like to retrieve all HMT and HDM in Leishmania...
ModeMood: Modeling Mood Disorders
Mood disorders such as bipolar and major depressive disorders affects 2-5% of the population worldwide. They are relapsing, major psychiatric illnesses with poorly understood neurobiology, typically incomplete treatment responses, and often unsatisfactory clinical outcomes, with a high risk of premature mortality due to suicide and clinical comorbidities. Its complex manifestations include marked disturbances of emotional regulation, sensory-perception as well as major changes in mood, thinking,...
Bioinformatic analysis of the adenylate cyclase CyaA toxin
The adenylate cyclase (CyaA) produced by B. pertussis, the causative agent of whooping cough, is one of the major virulence factors of this organism. CyaA plays an important role in the early stages of respiratory tract colonization by B. pertussis. This toxin uses an original intoxication mechanism: secreted by the virulent bacteria, it is able to invade eukaryotic target cells through a unique but poorly understood mechanism that involves a direct translocation of the catalytic domain across t...
Genetic profile of patients with dyslexia
Background: Dyslexia is characterized by difficulty with learning to read fluently and with accurate comprehension despite normal intelligence. It affects 5–10% of school-age children. Familial studies repeatedly showed that first-degree relatives of affected individuals have a 30–50% risk of developing the disorder. Twin studies showed that heritability was approximately 50% with a higher concordance rate for monozygotic twins compared to dizygotic twins. Although genetic f...
Characterization of an RNA binding protein of Listeria monocytogenes
We are analyzing a Listeria protein secreted in the supernatant. From cells transfected with this protein, after crosslinking, we have isolated RNA and found the protein in the RNA fraction. In addition, the protein binds several splicing factors in RNA dependent manner. Furthemore, the protein localizes to the nucleus. In this project, we have isolated the protein from the supernatant and from bacterial extract after growth in BHI. We have extracted the RNA from the supernatant fraction contain...
MacSyDBCapsule
Extracellular capsules constitute the outermost layer of some bacteria and establish the first contact between the cell and its environment. They are major virulence factors involved, amongst other, in antibiotic tolerance and immune escape. Bacterial capsules are also known to mediate unspecific cell-to-cell interactions between and across species and affect population structure and dynamics. Despite the great number of studies characterizing capsule diversity and their role during infection in...
Extraction of sequence information from published genomes of commensal bacteria
The microbiota of the gastrointestinal tract is a diverse mixture different species and strains of bacteria. We aim to identify regions of dissimilarity between two different bacterial strains to be able to quantitate their relative abundance and thus obtain information about their ability to cohabitate a common environment. In addition, we are interested in assessing the surface localised protein repertoir of specific species through a combination bioinformatic analysis and proteomics....
Statistical analysis of PI survey for the scientific direction
Statistical analysis of PI survey for the scientific direction...
Identification de SNP entre 2 souches bactériennes
Identification de SNP entre 2 souches bactériennes la souche sauvage et le révertant (Pseudomonas aeruginosa)...
Gene expression profiling in Kupffer cells
The liver is the biggest internal organ that is responsible for metabolism, detoxification and the defense between the host and the external environment. Thus the liver is also an immune organ, which constantly confronts conflicting demands of immunity against pathogens and tolerance to antigens metabolized locally and bacteria products derived from the gut. In homeostasis, many mechanisms ensure suppression of immune response in the liver, which include low expression levels of MHC molecules in...
Recombination among enteroviruses
Notre objectif est d'étudier comment la recombinaison génétique génère de la diversité au sein des écosystèmes d'entérovirus....
Automatic detection of antibiotic resistance genes
Linked with the project #7283 managed by Thomas Bigot, this proposal aims to detect antibiotic resistance genes in whole-genome sequence data of the bacteria deposited and stored at CIP. The CARD library (http://arpcard.mcmaster.ca) would be used to screen for common acquired resistance genes. Detection of point mutations in house-keeping genes and/or transporters would require specific queries from a fasta file continuously implemented by myself....
Research of SNPs to explain the non virulent phenotype of a mutant of L. interrogans serovar Manilae L495 affecting the expression of a protein not involved in virulence
We are studying mutants of L. interrogans obtained after random mutagenesis (M58) along with complemented mutant strain (C5M58), constructed using a secondary random mutagenesis. The M58 mutant was found non virulent in gerbils and mice, but the C5M58 strain showing restored expression of the protein, is also non virulent. We have another mutant strain (M1901) in the same gene that retained its virulence, which is the expected phenotype. We are interested in findings SNPs present in bot...
Graphical representation of co-expressed genes in various datasets
We have identified a candidate gene associated with increased resistance to a pathogen. This gene is poorly annotated in public databases. To get insight into its function we are focusing on genes that are co-expressed with this candidate gene in various datasets, including microarray collection on various mouse tissues or in a given tissue across inbred strains of mice. Indeed, coexpression is one of the central idea in gene expression analysis. The 'Guilt by association' principle states that ...
Role of PerR-regulated oxidative stress response in pathogen Leptospira virulence
Pathogen leptospires are responsible for the zoonotic disease leptospirosis. This neglected but emerging infectious disease has a worldwide distribution and affects people from developing countries, mostly under tropical areas. The clinical manifestations of this infection range from a febrile state to a severe life-threatening form characterized by multiple organ hemorrhages. More than one million cases of leptospirosis are currently reported annually in the word, with 10% of mortality. Duri...
Discovery of non-annotated transcripts in RNAseq data from Aedes Aegypti
The genome of the yellow fever mosquito (Aedes Aegypti) is not fully annoyed, and this project aims at discovering novel transcripts using RNAseq data....
Study of the early pathogenesis during Lassa fever in cynomolgus monkeys and its correlation with the outcome
Because of their increasing incidence, dramatic severity, lack of treatment or vaccine, complicated diagnosis, misreading of the pathogenesis, and need for a maximum containment, Viral Hemorrhagic Fevers (VHF) constitute a major public health problem. There is therefore an urgent need to further study VHF to understand the pathogenesis of the severe disease and the host responses involved in their control or in the dramatic damages. Among VHF, Lassa fever (LF) is probably the most worrying one b...
Quantitative temporal analysis of cellular proteins regulated by HBV in primary human hepatocytes
Despite effective prevention against HBV infection, 300 million people worldwide are chronic HBV carriers, of whom 25% will die of liver cirrhosis or hepatocellular carcinoma (HCC). Current treatments for chronic hepatitis B (CHB) are inefficient to completely clear the virus and liver cancer is a lethal disease, thus representing an area of highly unmet medical need. Viral persistence is due to the maintenance, in the nuclei of infected cells, of the viral nuclear DNA : the cccDNA that is no...
Caractéristiques génomiques de souches d’Escherichia coli productrices de BLSE associées à un portage persistant après un voyage en zone tropicale
Nous avons pu montrer grâce au projet de recherche clinique VOYAG’R (PHRC AOR 11101- IP Pr S. Matheron) que les voyages dans une zone tropicale constituaient un risque d’acquérir une Entérobactérie multi-résistante (EMR). Pendant 15 mois, la présence d’EMR a été recherchée chez 574 sujets avant et après leur voyage en zone tropicale. Les voyageurs porteurs au retour étaient suivis sur une période de 12 mois (1, 2, 3, 6 et 12 mois ou jusqu’à négativation). Au cours de leur s...
Comparative analysis of transcriptomic and proteomic data to study RNA and protein expression regulation during RVFV infection in mice.
In order to study a differential regulation of RNA and protein expression level during Rift valley fever virus (RVFV) infection in a murine model, we want to compare transcriptomic and proteomic analysis. ...
Gene ontology analysis of RNAseq data from uninfected and Leishmania-infected mouse macrophages
Gene ontology analysis of RNAseq data from uninfected and Leishmania-infected mouse macrophages. Scientific context During the course of cutaneous or visceral disease in humans or experimental animal models, the resolution of leishmanial infections or the control of parasite growth is dependent on appropriate innate and adaptive immune responses developed by the parasitized host. Leishmania largely evad...
Comparative analysis of gene expression pattern between samples of tumor and normal mice tissue
The post-translational modification by SUMO is an essential regulatory mechanism of protein function that is involved in most challenges faced by eukaryotic cells. Gene expression is particularly regulated by sumoylation as many SUMO substrates are transcription factors and chromatin-associated proteins, including histones. The emerging paradigm for the proposed work is that sumoylation controls multiple aspects of chromatin structure and function in response to external cues. According to this ...
Comparative analysis of gene expression in different human cell clones
The post-translational modification by SUMO is an essential regulatory mechanism of protein function that is involved in most challenges faced by eukaryotic cells. Gene expression is particularly regulated by sumoylation as many SUMO substrates are transcription factors and chromatin-associated proteins, including histones. The emerging paradigm for the proposed work is that sumoylation controls multiple aspects of chromatin structure and function in response to external cues. According to this ...
Differentiation of Shigella species from Escherichia coli by MALDI-TOF mass spectrometry
Shigella species and E. coli are very closely related bacteria belonging to the Enterobacteriaceae family. Phenotypically they are very similar and genotypically they could be considered the same species. The differentiation of Shigella species from E. coli is a significant diagnostic challenge for the clinical microbiology laboratories. They increasingly use maldi-tof mass spectrometry-based microbial identification systems but the latter are currently not...
Single cell analysis of HIV-specific CD4+ T cell differentiation
HIV infects and depletes CD4+ T cells, leading to a progressive loss of adaptive immune responses and ultimately to AIDS. In addition, HIV preferentially targets HIV-specific CD4+ T cells, resulting in an attrition of the very cells that should orchestrate the antiviral immune response. Due to this preferential depletion, HIV-specific CD4+ T cells are few and remain incompletely characterized. The emergence of single cell technologies opens the opportunity for an in depth analysis of the rare sp...
JASS: an online tool for the joint analysis of GWAS summary statistics
In recent years, large genome-wide association studies (GWAS) have been successful in identifying thousands of significant genetic associations for multiple traits and diseases1. In the course of this endeavor, sample size has proven to be the key factor for identifying new variants. For example, GWAS of body mass index (BMI), now including up to 350,000 individuals from more than 100 cohorts, have been able to identify genetic variant that explain as low as 0.02% of BMI variance2. While standar...
- Vincent Guillemot
- Hanna Julienne
- Pierre Lechat + 1 operator
Immune control of the gut microbiota and lifespan of A. stephensi.
Anopheles mosquitoes are the vectors of Plasmodium parasites, the etiological agents of malaria in humans. In Anopheles gambiae, a major vector in Africa, parasite transmission is largely under genetic control. We have previously shown that a gene family is implicated in the immune control of the parasite in this vector. The response of the family members is pathogen-specific, with one controlling P. falciparum infection and the other controlling rodent parasites. Recently, the genome of Anophel...
Characterization of the specific TCR repertoire preferentially expressed in spontaneously controlled HIV infection
The rare patients who spontaneously control HIV replication in the absence of therapy show signs of a particularly efficient cellular immune response. To identify the molecular determinants underlying this response, we characterized the TCR repertoire directed at the most immunodominant CD4 epitope in HIV-1 capsid, Gag293. HIV Controllers from the ANRS CO21 CODEX cohort showed a highly skewed TCR repertoire characterized by a predominance of the TRAV24 and TRBV2 variable gene families. Controlle...
Utilize mouse models to study infection by HIV-1
We previously showed that humanized immune system (HIS) mice generated in Balb/c Rag2-/-γc-/- SIRPNOD (BRGS) recipients are susceptible to HIV-1 infection (X4 and R5 isolates) and maintain circulating HIV-1 in the plasma, resulting in a dramatic depletion of human CD4+ T cells. We also characterized features of HIV physiopathology in this model. Human thymocyte subsets developing in the thymus of HIS mice appear phenotypically normal,...
A novel MacSyFinder module for detection of bacterial capsule systems on the future Galaxy platform.
Extracellular capsules constitute the outermost layer of some bacteria and establish the first contact between the cell and its environment. They are major virulence factors involved, amongst other, in antibiotic tolerance and immune escape. Bacterial capsules are also known to mediate unspecific cell-to-cell interactions between and across species and affect population structure and dynamics. Despite the great number of studies characterizing capsule diversity and their role during infection in...
Add unit tests to IntegronFinder
Integrons drive the spread of antibiotic resistance genes in bacterial populations. While their role is widely known (integron+antibiotic+resistance in PubMed gives > 1700 hits), there was no software available to identify integrons and their different components. We have made integronFinder (with Bertrand Néron) for this (Cury, NAR, 16). We would like to make improvements to IntegronFinder:
- Unit tests to facilitate the development of the tool. Especially since Jean Cury (the m...
Project keywordManagerOperators
Development of a new web interface for ARIA
The ARIA (Ambiguous Restraints for Iterative Assignment) software, developed at the Structural Bioinformatics Unit, automatizes the treatment of NMR data and protein structure calculation by molecular dynamics simulation. To enhance the visibility of the software, it is necessary to develop a new web interface where users will be able to easily manage their data, perform calculations and analyze the results of the ARIA calculations....
In silico analyses of a novel LincRNA potentially involved in type I IFN response
We study the regulation of type I interferon (IFN) response in humans and in particular the functioning of a key negative feedback regulator, USP18. A recent article reported on a predicted 897nt-long LincRNA (long intergenic non coding RNA) that may target USP18. We have collected information for this LincRNA (genomic locus, putative transcript variants, sequence similarities with USP18 RNA, predicted ORFs, homologies with other genes, etc). To draw a guideline for wet lab experiments, we ne...
Development of top-down proteomics for clinical microbiology
Rapid and accurate identification of microorganisms is a prerequisite for appropriate patient care and infection control. In the last decade, Mass Spectrometry (MS) has revolutionized the field of clinical microbiology with the introduction of MALDI-TOF for rapid microbial identification. However, MALDI-TOF MS suffers from important limitations. Some bacteria remain difficult to identify, either because they do not give a specific profile or because the database lacks the appropriate referenc...
Analysis of DNA methylation in the presence and absence of antibiotics in wt and mutant V. cholerae.
Thanks to RNA-Seq experiments we identified a new orphan DNA methylase (not associated with a restriction enzyme) that is highly upregulated in the presence of low concentrations of aminoglycosides in V. cholerae. The results allow us to consider a differential DNA methylation profile depending on the environment (with or without antibiotics), which can possibly correspond to a novel epigenetic control of the response....
Detection of virulence Genes and genes of interest in Bacillus cereus
Bacillus cereus is ubiquitous in nature, and while most isolates appear to be harmless, some are associated with food-borne illnesses, periodontal diseases, and more serious infections. Moreover, emerging B. cereus strains that cause anthrax-like disease have been isolated in Cameroon and Côte d’Ivoire. These strains are particular, because although they belong to the B. cereus species genetically speaking, they harbor two plasmids, pBCXO1 and pBCOX2, that are very ...
optimisation d\'un programme sous R
Nous avons créer un programme sous R pur l'analyse non supervisé de fichier de cytométrie et nous avons besoin d'aide pour optimiser ce programme. Nous avons également besoin de conseils pour optimiser le clustering. Nous avons déjà rencontré Hugo Varet....
Activation of plasmacytoïd dendritic cells by arenaviruses : transcriptomic analysis
Lassa virus (LASV) is an arenavirus causing hemorrhagic fever in human. 300 000 to 500 000 cases of LASV infection are reported every year in western Africa, including 5 000 to 6 000 deaths. LASV is highly pathogenic, and no vaccine or treatment is available in endemic areas. LASV pathogenesis mechanisms are not well documented, and further investigations are needed to understand viral and immunological factors involved during infection. As previously shown by studies conducted on patients a...
Genomic analysis of bacterial evolution
We are interested to look at evolution of bacteria in presence of bacteriophages within the gastrointestinal tract of animals. ...
Genomic differences of the same strains preserved in different culture collections
Bacterial strains used for quality control (e. g. fertility and viability controls) are recommended in different ISO norms. Each strain is at least deposited in two different collections. So, equivalent strains are found in different collections. Their preservation is generally performed by freeze-drying. As control strains, they are much distributed, thereby, new freeze-dried batches have been done in the course of time. The subm...
Modeling mitochondrial metabolism dormant Cryptococcus neoformans
Cryptococcus neoformans is a ubiquitous yeast present in the environment that is able to interact closely with numerous organisms including amoeba, paramecium or nematodes. The interaction with these organisms shaped its virulence with acquisition of infectious properties as a consequence especially in mammals . The ability to survive nutrient starvation, oxidative stress, desiccation, both in the environment and during infection, indicates a high level of physiological and metabolic ...
Development of a web application and new functionalities for the maintenance and curation of iPPI-DB
A new version of the iPPI-DB, a manually curated database that contains the structure, some physicochemical characteristics, the pharmacological data and the profile of the PPI targets of several hundred modulators of protein-protein interactions.
Determination of phage termini using NGS
See below ...
Cytokinesis study
Our team is dedicated to understanding the mechanisms involved in cytokinesis. A screen has been performed and should help us better understand this process....
Gene Ontology and sequence analysis of proteomics data on mycolactone effects on dendritic cells.
Mycolactone, the lipid toxin produced by Mycobacterium ulcerans, has recently been shown to target the Sec61 transolcon, blocking protein translocation accross the ER membrane. As Sec61 has also been proposed as a critical mediator in cross-presentation in dendritic cells, this analysis aims to analyse mycolactone effects on the proteome of dendritic cells....
RNA analysis underlying phenotype of mouse model for autism
After the behavioural characterisation of the Shank3 KO cohort, we extracted and dissected different region of the brain: cort...
Mapping the genomic architecture of human neuroanatomical diversity
Our recent analyses suggest that the genetic determinants of human neuroanatomical diversity are massively polygenic. Like other quantitative traits such as height – but also IQ or ASD risk – neuroanatomical diversity seems to result from the aggregated effect of thousands of frequent variants, each of small effect. GWAS should then require populations of hundreds of thousands of individuals to start to detect the individual variants. GCTA (genomic complex trait analysis) offers an alternati...
Insect Vector Genomics
Insect vectors durably transmit many important human and animal diseases. Insects are mobile, adaptable and difficult to control, which makes them efficient vehicles for disease emergence, spread and maintenance. Genomic tools have been applied to the study of vectors and vector control, and some insects such as the African malaria vector Anopheles gambiae have now become new model organisms for natural host-pathogen interactions. We study mosquito vectors of malaria and arboviruses, which gener...
Transcriptional regulation of innate lymphoid cell plasticity versus differentiation
Over the last years, innate lymphoid cells (ILC) have been increasingly investigated. Despite the absence of antigen specific receptors, they belong to the lymphoid lineage and represent important sentinels for tissue homeostasis and inflammation. They contribute to numerous homeostatic and pathophysiological situations via specific cytokine production. ILC are currently divided into three groups based on the expression of specific transcription factors and secretion of cytokines. We focus this ...
PhageTermini: a Fast and User-friendly Software to Determine Bacteriophage Packaging Mode and Termini
The PhageTermini software was developed to allow biologists acquire valuable information on bacteriophage termini sequences and packaging mode using phage sequenced with the Illumina TruSeq technology....
Regulation of HIV-1 integration selectivity by chromatin
Integration of the viral reverse-transcribed genome into the genome of infected cells is an essential step of retroviral replication and is performed by a viral-encoded enzyme, named integrase (IN). In the case of HIV-1, IN is a new and efficient anti-viral target. The selectivity of this enzyme for its cellular genomic sites is also a major parameter of HIV replication and is regulated by several cellular parameters. One of them is chromatin, and different levels of this nucleoprotein complex a...
Identification of genes involved in the attenuation of virulence of rough M. abscessus Tn5 mutants in zebrafish
Mycobacterium abscessus is the fast growing mycobacterial species the most frequently associated with lung infection, characterized by severe and very inflammatory cases, after a slow and chronic infectious process. The Cystic Fibrosis patients are particularly susceptible to this bacteria. M. abscessus can exist in a smooth (S) or rough (R) shape depending respectively on the presence or absence of glycopeptidolipids (GPL) associated with the wall of the bacillus. These GPL ar...
Identification of promoteur-overlaping antisense transcription
Analysing the transcriptome of exponentially grown or stationary phase yeasts in a genetic background that stabilises pervasive transcipts, we identified a first subset of ≈ 140 antisense transcripts anti-correlated with gene transcripts that are specifically expressed in quiescence. We are further investigating whether these genes are subject to a transcriptional interference and what are the mechanisms underlying this regulation. More in detail, we would like to analyse the loci whe...
Tac4, a new RNA helicase involved in translation control?
We are interested in the cytoplasmic quality control of gene expression and more especially into the behavior of aberrant peptides which could be generated from non-conform translation events. We are now investigating the role of a Saccharomyces cerevisiae RNA helicase protein that we named Tac4 (for Translation Associated Component 4). We showed that this protein is involved in translation. We demonstrated, by sucrose gradient and affinity purification that Tac4 interacts with the ribo...
Impact of hepatic inflammation on microbiota
The aim of the project is to search for the effects of hepatic inflammation on microbiota....
Measles virus protein C interplay with cellular apoptotic pathways; applications for cancer treatment
Measles virus protein C interplay with cellular apoptotic pathways; applications for cancer treatment....
Regulation of Sirtuin 2-dependent histone deacetylation during bacterial infection
One of the best models for the study of bacteria-host interactions is Listeria monocytogenes. One interesting facet of this bacterium is its ability to modify host chromatin. Recently, we have shown that Listeria causes a drastic deacetylation of histone H3 on lysine 18 (H3K18dc). Interestingly, to impose this modification, Listeria highjacks previously undescribed host machinery: the host protein sirtuin 2 (SIRT2) is relocalized to the nucleus where it causes genes repression during infection. ...
Identification of Tac4 mRNA targets
We are interested in the cytoplasmic quality control of gene expression and more especially into the behavior of aberrant peptides which could be generated from non-conform translation events. We are now investigating the role of a Saccharomyces cerevisiae RNA helicase protein that we named Tac4 (for Translation associated Component 4). We showed that this protein is involved in translation. We demonstrated, by sucrose gradient and affinity purification that Tac4 interacts with the ribo...
Deciphering the composition dynamics of infant gut microbiome
As a part of BIRDY program (http://www.charliproject.org/), this project aims to study the microbiome composition and its dynamics in early infancy in Madagascar. It will provide genomic knowledge on antibiotic resistant strains and resistance genes circulating in this island. It will identify factors influencing the outgrowth of pathogenic bacteria, including ESBL-PE and decipher the role of the gut microbiome. The developed comprehensive modeling framework will be easily adaptable to other epi...
Analysis of the transcriptome of malaria parasites
We are interested in determining the differences in the transcriptome of select developmental stages of the malaria parasite, Plasmodium....
Novel protein interaction in the assembly of photosynthetic prokaryotic complexes
This project is intended to explore the novel protein interactions that are involved in the protein folding in cyanobacteria. Slr0286 was previously identified as a protein interacting with the D2 protein of photosystem 2 and affecting its functional assembly and stability in Synechocystis sp. PCC6803. The gene that encodes this protein appears to be in one operon with slr0285 in all strains where these two genes are found. This may suggest the functional relationship between the produ...
Dissecting the peptidoglycan trafficking machinery using gene trap mutagenesis in near-haploid human cells
It has been found in the past that the peptidoglycan (PGN) degradation fragments DAP-containing muramyl tripeptide (M-triDAP) and muramyl di-peptide (MDP) stimulate innate immune receptors Nod1 and Nod2. However, it remains to be clarified how the fragments reach Nod1 and Nod2, since these receptors are intracellular. The aim of the project is thus to investigate novel factors in peptidoglycan signalling, using gene trap mutagenesis in human near-haploid cells to randomly knock out genes and do ...
IgBlast on Galaxy
We would like to be able to use IgBlast on the Galaxy platform. We are studying B cells in adaptive immune response, and are particularly interested in the antibodies termed as broadly neutralizing antibodies (bNAbs). By definition, these antibodies can neutralize most known HIV-1 strains, and are produced by rare infected individuals several years post-infection. We are currently investigating the bNabs immunoglobulin repertoire by focusing our NGS (454 pyrosequencing) analysis on immunog...
Identification of new or unexpected pathogens, including viruses, bacteria, fungi and parasites associated with acute or progressive diseases
Microbial discovery remains a challenging task for which there are a lot of unmet medical and public health needs. Deep sequencing has profoundly modified this field, which can be summarized in two questions : i) which pathogens or association of pathogens are associated with diseases of unknown etiology and ii) among microbes infecting animal (including arthropod) reservoirs, which ones are able to infect large vertebrates, including humans. We are currently addressing these two questions and o...
Diffusion des mutations de résistance du VIH : modèles et méthodes d’estimation
Les mutations de résistance aux traitements apparaissent sous l’effet de la sélection. Ces mutations sont transmises, les patients pouvant être infectés par des souches déjà résistantes à certains traitements. Ces mutations posent des problèmes considérables en limitant l’arsenal des traitements disponibles, pour les individus comme pour la population sur le long cours. Dans le cas du VIH, nous avons travaillé sur la transmission de ces mutations au sein de la population anglaise,...
Molecular analysis of muscle stem cells
Skeletal muscle stem cells constitute a population of cells with heterogeneous properties. Interestingly, muscle stem cells have a remarkable capacity to regenerate muscle fibres after regeneration. We are performing a molecular analysis of these stem cells....
Nanotherapeutics for multidrug-resistant tuberculosis
Tuberculosis (TB) still remains a major public health problem with estimated 9 million incident cases and 1.5 million deaths in 2014 (WHO, Global Tuberculosis Report 2015). More worrisome is the emergence of multi drug resistance (MDR), or even extensively resistant (XDR) M. tuberculosis strains worldwide. The standardized treatment of pan-susceptible tuberculosis is the administration of two antibiotics (rifampicin and isoniazid) for six months, accompanied by two ad...
Host gene regulation in response to Listeria monocytogenes infection
Listeria monocytogenes is a gram-positive bacterium responsible for the food-borne disease listeriosis. This pathogen can invade and replicate in the cytoplasm of both macrophages and non-professional phagocytes. In order to better characterize the host response to Listeria, we are using microarrays to identify genes and cytokines up or downregulated during infection....
Beautiful Interface and System To Report and Organize [Education]
...
Deconvolution of synthetic chromosomes in 3D
Our aim is to characterize the fine organization of chromatin on homologs during meiotic prophase, and how this organization is functionally related to recombination....
Methylome analysis of a human progeroid disease for the detection of progeroid-specific alterations and their link with regular ageing
The mechanisms governing ageing, which is a multifactorial process, have not been resolved and constitute a fundamental open question in cell and organismal biology. Exceptionally, in rare genetic diseases like the Cockayne syndrome (CS), ageing is dramatically accelerated. We have recently identified a novel pathway that is altered in cells from CS patients and is not affected in a linked disease (UVSS) that is not associated with precocious ageing. This is a unique case in the literature of di...
Collaboration with the hub to develop ChiPseq and ATACseq analysis pipelines
The Transcriptome and EpiGenome platform has a strong expertise in the bioinformatical and statistical analysis of RNA seq data. Nevertheless, we have more and more demands for the use of NGS to characterize the epigenome (using ChIPseq approach) or chromatine accessibility (by ATAC-seq) .We thus need to further develop and validate analysis workflows for these types of data. This project aims at developing and formalizing collaboration between the platform and some experts in this field at ...
Comparative analysis of the virulence plasmids of Shigella Spp. and entero-invasive Escherichia coli
Context. Bacteria of the genus Shigella and strains of entero-invasive Escherichia coli (EIEC) are responsible of bacillary dysentery (shigellosis) in humans. Although (very) closely related to E. coli, the genus Shigella is divided in four "species": S. boydii, S. dysenteriae, S. flexneri and S. sonnei. Most virulence determinants enabling these bacteria to enter into and disseminate within epithelial cells are encoded by a 200-kb virulence plasmid (VP). The first complete sequence of a VP (pWR...
Beautiful Interface and System To Report and Organize
The Hub needs a project management system that fulfills the following needs :
- provides a web page for project submission
- keeps track of all the information associated with submitted projects including:
- contact information of the applicant and the PI if different
- minutes of meetings with applicants
- project description (public and private)
- decription of the different steps that are planned to carry out the project. Information abo...
Project keywordManagerOperators
Label-free quantitative proteomics of Human Macrophages infected by M. tuberculosis
Label free quantification of proteins after the infection with M. tuberculosis. Macrophages isolated from seven patients were used in this study. Four conditions were compared....
Rift valley fever NSm protein functional study
Screening for NSm function in infected mammalian cells by proteomic analysis....
Zebrafish microbiota
16S OTU assignment and statistical analysis of zebrafish microbiota in different experimental conditions....
Comparative genomic and phylogenetic analysis of Clostridium botulinum strains
We submitted an article about the diversity of Clostridium botulinum strains based on MLST analysis. One reviewer of the article asked further study of our NGS data....
Patho-evolution of mycobacterial strains
Mycobacterium tuberculosis is an extremely successful, aerosol-transmitted human pathogen, thought to have evolved from a Mycobacterium canettii-like progenitor. In contrast, extant M. canettii strains are rare, genetically diverse and geographically restricted mycobacteria of only marginal epidemiological importance. Comparative genome studies of several Mycobacterium canettii strains previously identified genetic events that contribute to the contrasting evo...
Deciphering dormancy in Cryptocococcus neoformans
Project context and summary : Cryptococcus neoformans is a sugar-coated yeast that is able to interact closely with numerous organisms in the environment including amebae, paramecium of nematodes. The interaction with these organisms probably shaped its virulence. The ability to survive nutrient starvation, oxidative stress, desiccation, both in the environment and in humans, indicates a high level of physiological and metabolic plasticity of the yeast. In humans, after...
Environmental and human surveillance of polioviruses, VDPVs, and other enteroviruses in Madagascar during the switch from tOPV to bOPV
Poliomyelitis has been a major public health concern and currently, efforts are being made towards eradicating wild poliovirus type 2 (WPV2). A global switch from trivalent oral poliovirus vaccine (tOPV) to bivalent oral poliovirus vaccine (bOPV without PV2) is planned to take place this year in countries, like Madagascar, where epidemics of type 2 pathogenic circulating vaccine-derived polioviruses (cVDPVs) occur when low polio vaccine coverage allows the circulation and genetic drift of vaccin...
Recherche de SNP chez une souche de leptospira biflexa d'interêt
Recherche de SNP chez une souche de leptospira biflexa devenue résistante à un bactériophage....
Genomic analysis of small orfs of unknown function
One project of our laboratory is to characterize the function of small proteins specifically expressed in nongrowing Salmonella cells under the tight control of SigmaS. Our current works focus on small proteins secreted or targeted to the membrane since their characterization might reveal novel aspects of membrane functions and secretion in persistent bacteria, including pathogens. The proposed project is an extension of a former project on the phylogenetic distribution of the smal...
Prediction of RNA-RNA interactions between a family of GC-rich ncRNAs and nascent transcripts of virulence genes in Plasmodium falciparum
In Plasmodium falciparum a virulence gene family with 60 var genes codes for the PfEMP1 surface proteins, which undergo antigenic variation. This epigenetically controlled mechanism promotes immune evasion of the parasite. As ncRNAs are emerging as relevant regulators of gene expression we are investigating a GC-rich ncRNA gene family consisting of 15 highly homologous members all positioned next to var gene clusters. We recently found that GC-rich ncRNA transcript ass...
HSC3D
Detection of nucleic acids at the single cell level using microscopy has now reach high throughput levels which promise exciting discoveries concerning the functionning of the genomes. The HSC3D project funded by the CITECH in the Pasteur institute aims at multiplexing nucleic acid detection by Fluorescence In Situ Hybridisation (FISH). This necessitates libraries in the range of tens of thousands of 100mer DNA oligonucleotides which will be synthesised by digital lithography. Several constrai...
Comparative genomic and phylogenetic analysis of Clostridium baratii strains
The first two cases in France of botulism due to Clostridium baratii type F were identified in November 2014, in the same family. Both cases required prolonged respiratory assistance. One of the cases had extremely high toxin serum levels and remained paralysed for two weeks. Investigations strongly supported the hypothesis of a common exposure during a family meal with high level contamination of the source. However, all analyses of leftover food remained negative...
Gene Expression analysis
assess the faisability of the chip analysis to our samples from laser capture microdissection of the mouse intestine, of diverse quality and preparation levels...
BrainEvo
Recent progress in sequencing and bioinformatics methods have given access to ancient DNA. This project aims at understanding the differential evolutionary pressure on the key proteins implicated in the nervous system....
Bioinformatic analysis of phospholipase A2 (PLA2) from P. falciparum
Background: PLA2 is known to regulate vesicle secretion in diverse eukaryotic cells. We are interested in determining the putative role of PLA2 in secretion of apical vesicular organelles called micronemes and rhoptries in P. falciparum merozoites. PLA2 inhibitors such as 4-BPB are known to block growth of the related Apicomplexan parasite Toxoplasma gondii. There are 3 annotated PLA2 genes in the P. falciparum genome database (Pf3D70209100, PF3D71...
mechanism of toxin production by Klesiella pneumoniae
We're interested in the production of a toxin by Klebsiella pneumoniae. We have a mutant unable to produce this toxin, and would like to identify the mutation responsible of this inability....
secretome analysis of human intestinal cells during shigella invasion
Shigella is an enteroinvasive bacterium that induces bacillary dysentery. It invades human intestinal epithelial cells causing the inflammatory destruction of the colonic epithelium. Our previous work reported that Shigella inhibits the secretion of its host cell (Mounier et al Cell Host Microbes 2012) via several virulent proteins injected by the bacterium such as IpaJ and VirA. These two effectors may have redundant action. Thus, to address the effect of
Development and use of statistical programs to analyze RNA-Seq data produced at the Transcriptome & Epigenome Platform
The Transcriptome & Epigenome Platform is dedicated to the development and use of high throughput approaches for transcriptomics and epigenomics studies. The platform is accessible to any research team from the Pasteur Institute (80% of the projects) as well as from outside. It is involved (most often as collaborator) in several projects funded by the ANR, Microbes and Brain, ERANET and by the Pasteur Institute in the framework of the PTR programs. Next Generation Sequencing (NGS) based on t...
Development and use of statistical programs to analyze RNA-Seq data produced at the Transcriptome & Epigenome Platform
The Transcriptome & Epigenome Platform is dedicated to the development and use of high throughput approaches for transcriptomics and epigenomics studies. The platform is accessible to any research team from the Pasteur Institute (80% of the projects) as well as from outside. It is involved (most often as collaborator) in several projects funded by the ANR, AVIESAN and by the Pasteur Institute in the framework of the PTR programs. Next Generation Sequencing (NGS) based on the Illumina technology ...
Analysis of sequencing data from a Leishmania donovani cosmid library
Chromosome amplification is commonly used by Leishmania during adaptation to environment. In this context it is challenging to look for genes relevant for parasite virulence/attenuation/drug resistance... To restrict this chromosomal amplification, a cosmid approach (CoSeq) has been chosen to select for genes that provide fitness gain to Leishmania donovani parasites in culture and in the animal. Therefore, a cosmid library has been generated with genomic DNA from the parasites which needs t...
Mining the Plasmodium genome to identify novel blood stage antigens for use as malaria vaccine candidates
Malaria remains a major problem in many tropical countries with Plasmodium falciparum accounting for up to 1 million deaths, primarily in infants and children residing in endemic areas of sub-Saharan Africa. P. vivax, the other important species for human malaria is geographically more widespread and causes 80-100 million cases of malaria each year. All the pathology related to malaria is attributed to the blood stage of the parasite life cycle during which Plasmodium merozoite...
Development of a bioinformatics workflow dedicated to the analysis of the viral metagenome: from NGS raw data to the identification of novel viruses
The aim of this project is to implement, at the level of the research units, a bioinformatics workflow dedicated to the analysis of the microbiome, and of the virome in particular, based on Next Generation Sequencing (NGS) data (Illumina technology). This workflow will be applied in different contexts, from the identification of nucleotide sequences belonging to a novel or emerging pathogen (mainly viruses) presente in a clinical sample (such as serum or cerebrospinal fluid), to the determinatio...
individual-nucleotide resolution Cross-Linking and ImmunoPrecipitation (iCLIP) of Argonaute proteins in C. elegans
We are mapping the interactions between argonaute proteins and their target RNAs at nucleotide resolution to reveals preferential binding sites on RNAs...
Reconstruction of archaeal genomes from environmental metagenomic data
A large fraction of diversity of the Archaea is still poorly explored. We are targeting environmental samples to extract genomic data of archaeal lineages of specific interest from an evolutionary point of view. We will probe available sequence data from public environmental metagenomics databases to identify specific lineages. In parallel, we will produce our own data from selected environmental samples containing these lineages. These data will allow filling up poorly explored branch...
Systems Biology of Cell Infection by the Bacterial Pathogen Listeria monocytogenes
In the context of the Swiss consortium InfectX (www.infectx.ch), Javier PIZARRO-CERDA previously performed siRNA, microRNA, drug screens and proteomic analyses to investigate signaling pathways modulating invasion of host cells by the bacterial pathogen Listeria monocytogenes. In a first consortium study, based on results from drug and siRNA screens targeting the human kinome, we identified major kinases which up- or down-regulate cell invasion by L. monocytogenes and by 7 additional bacterial a...
Listeriomics - Development of a web platform for visualization and analysis of Listeria omics data
Over the past three decades Listeria has become a model organism for host-pathogen interactions, leading to critical discoveries in a broad range of fields including virulence-factor regulation, cell biology, and bacterial pathophysiology. More recently, the number of Listeria “omics” data produced has increased exponentially, not only in term of number, but also in term of heterogeneity of data. There are now more than 40 published Listeria genomes, around 400 dif...
Host Range Database
We wish to offer to the community of microbial virologists a place where they can store and find results of host range determination for microbial viruses...
Determination of SNPs in 6 genomes of Leptospira kirschneri serovar grippotyphosa
Recently 6 strains of Leptospira kirschneri ser grippotyphosa have been sequenced, assembled and annotated. These strains possess 99% genome similarity, but their provenance, virulence and growth characteristics remains different. We would like analyze the SNP of each strain using the SynTView/SNPView tool. ...
Factors determining HIV seeding in CD4+ T cell subpopulations
The objective of this study is to evaluate how the different programming of distinct CD4+ T cell subsets affected their susceptibility to HIV infection and the survival of infected cells. Dr. Saez-Cirion's Team evaluates how the metabolic state of CD4+ T cells and the regulation of cellular factors shape the distribution of the HIV reservoir in distinct CD4+ T cell subset. This project uses new technologies and reagents to analyze cells from uninfected donors, and from HI...
ANALYSIS OF TRANSCRIPTIONNAL MODULATIONS INDUCED IN C57BL/6 BONE-MARROW DERIVED MACROPHAGES INFECTED BY LEISHMANIA AMAZONENSIS IN PRESENCE OR ABSENCE OF INFLAMMASOME-ACTIVATING CONDITIONS
Aim : When L. amazonensis (L.am.) amastigotes infect BMDMs, they induce multiple strategies to allow their survival and multiplication. This project aims at deciphering the transcriptional modulations induced after three days of in vitro infection of C57BL/6 BMDMs with L. amazonensis (L.am.) amastigotes, in unstimulated conditions, or conditions that induce NLRP3 inflammasome activation....
ANALYSIS OF TRANSCRIPTIONAL MODULATIONS RELATED TO CELL DEATH PROCESSES IN MURINE BONE-MARROW DERIVED MACROPHAGES AND DENDRITIC CELLS INFECTED BY LEISHMANIA AMAZONENSIS
Aim : In vitro infection of innate immune cells by L. amazonensis (L.am.) seems to be associated to an increase in resistance to cell death of infected cells. This project aims at deciphering the impact of in vitro L. amazonensis (L.am.) amastigotes infection on cell death processes including apoptosis, autophagy, pyroptosis and necroptosis in different host cells, i.e. Bone-marrow- derived macrophages (BMDMs) and dendritic cells (BMDCs) after one day of infection. ...
Transciptomic analysis of dendritic cell response during Lassa virus infection
Lassa virus (LASV) is an arenavirus causing hemorrhagic fever in human. 300 000 to 500 000 cases of LASV infection are reported every year in western Africa, including 5 000 to 6 000 deaths. LASV is highly pathogenic, and no vaccine or treatment is available in endemic areas. LASV pathogenesis mechanisms are not well documented, and further investigations are needed to understand viral and immunological factors involved during infection. As previously shown by studies conducted on patients a...
Interactions and dynamics of fungal and bacterial microbiome in healthy people
The gastrointestinal tract of humans is colonized by hundreds of microbial species, - bacteria, archaebacterial, fungi, protozoa and viruses -, collectively named the gut microbiome. The intestinal commensal bacteria have an important role in metabolic processes and contribute to colonization resistance against intestinal pathogens. Fungi are usually considered to be a minor component of the global microbiome. However, the mycobiome (fungal component of the entire microbiome) has been in fact li...
Massive amplification at an unselected locus accompanies complex chromosomal rearrangements in yeast
Gene amplification has been observed in different organisms in response to environmental constraints, such as limited nutrients or exposure to a variety of toxic compounds, conferring them specific phenotypic adaptations by increasing expression levels. But the presence of multiple gene copies has generally not been found in natural genomes in absence of specific functional selection. Here we show that the massive amplification of a chromosomal locus (up to 880 copies per cell) occurs in absence...
SNP based analysis of French Bordetella pertussis isolates: comparison of isolates producing all the vaccine antigens to isolates producing only some of them.
Whooping cough is a vaccine-preventable disease due to Bordetella pertussis. Even if vaccination has allowed the control of the disease, isolates are still circulating and cyclic increases of incidence are observed every 3 to 5 years even in vaccinated countries. Most developed countries now use acellular vaccines containing 3 to 5 vaccine antigens (pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) fimbrial proteins (FIM2/FIM3)) that have replaced whole cel...
Bio-informatics support for the LeiSHield project
BioHub LeiSHield project This proposal summarizes the contribution of the BioHub to the LeiSHield action that may be carried out by a single BioHub Leishmania coordinator (Giovanni Bussotti). The coordinator will be implicated in the following actions: 1) Establish the link between LeiSHield members and the BioHub team for all questions regarding data analysis and interpretation. The coordinator will present to the BioHub the bio-informatics needs of the LeiSHield partners. Short (easy) ta...
Immunovax
Analysis of the immune response to yellow fever 17D vaccination...
RNAseq analysis-gene ontology enrichment Clostridium tetani
An experiment of RNAseq was performed in triplicate with the strain A of Clostridium tetani in TGY (low production of toxin) and MS (high production of toxin) at 24 and 48 h of culture. This RNAseq was performed in the Pasteur platform PF2. Different comparisons were performed: MS-48h vs MS-24h, TGY-48h vs TGY-24h, TGY-24h vs MS-24h and TGY-48h vs MS-48h. Excel files with differentially expressed genes were provided. For each comparison there are three excel files: complete.xls (contains re...
Meta-analysis of dengue transcriptomic data
We would like to uncover associations between transcriptomic features and dengue infection outcome. In order to do so, we want to take advantage not only of our data but also of all publicly available data. A main challenge is to translate the measurements across different transcriptomic technologies into a summary expression level per gene. For this C3BI project we would like to concentrate on the problem of mapping probe IDs into a common identifier for all experimen...
Antibody sequencing by MS: Automation of analysis
Protein sequencing by MS: Automation of analysis...
The contribution of ecological variation to the microbiome of Ae. aegypti
We are comparing the bacterial communities of domestic and sylvatic breeding sites and midguts of Aedes aegypti collected in Gabon....
A long-term mission for an assigned CIH-embedded bioinformatician to provide bioinformatic support to the CIH community
The Center for Human Immunology (CIH) supports researchers involved in translational research projects by providing access to 16 different cutting edge technologies. Currently, the CIH hosts over 60 scientific projects coming from 8 departments of the Institut Pastuer and 5 external teams. In order to respond to the growing needs of these projects in the area of single cell analysis, the CIH has introduced a significant number of single-cell/single-molecule technologies over the past 2-3 years. ...
Variant effects on influenza virus proteins
Collect statistics on variants found in different strains of influenza virus. Determine variant effects to the protein sequence....
Comparative genomic and phylogenetic analysis of 14 Clostridium tetani strains
The genome of C. tetani contains a chromosome of approximately 2,8Mb and a large size plasmid (74 kbp) harboring the tetanus-toxin gene. The genome of the strain E88 was sequenced and annotated (PNAS 2003, 100:1316-1321). We have sequenced and performed a first comparison of the genomes of three additional strains (Res Microbiol 2015, 166:326-331). Fourteen additional C. tetani strains were sequenced including historical strains (1952-1968) and recent French clinical isolate...
Un workflow pour l'analyses des polymorphismes des souches de grippe saisonnier.
analyses et classification des échantillons grippales....
L'analyses phylogénétique par séquence protéique, temporal et géographical
L'Analyses phylogénétique par séquence protéique, temporal et géographique des échantillons grippales avant et après l’épidémie de 2009....
Analyses fonctionnel des protéines humains de type ubiquitin.
Analyses fonctionnel des protéines humains de type ubiquitin qui interagir avec les virales protéines de la grippe...
Analyses protéine-protéine interactions
L'extraction des protéines humaines qui interagir avec des protéines virales par le séquençage des barcodes associés avec les protéines humaines et virales. Analyses structurales des protéines virales et humain pour trouver les sites d’accrochage....
Deciphering dormancy in Cryptocococcus neoformans
Cryptococcus neoformans is a sugar-coated yeast that is able to interact closely with numerous organisms in the environment including amebae, paramecium of nematodes. The interaction with these organisms probably shaped its virulence. The ability to survive nutrient starvation, oxidative stress, desiccation, both in the environment and in humans, indicates a high level of physiological and metabolic plasticity of the yeast. In humans, after primary infection during childhood, the ...
Variant detection on NGS data
The goal of this project is to set sequence analysis tools to evaluate the frequency of mutations within a pool of bacteriophage genomes sequenced by NGS....
The Physiological Consequences of Altering Bacterial Cell Wall Synthesis
Currently there is increased focus for developing novel antibacterial strategies. The demand is driven by the rise in antibiotic resistance bacteria and many Gram-negative bacteria are on the list of increasingly drug resistant agents. A major target of successful antibiotics is the bacterial cell wall. The target of these drugs is often defined but what is much less understood is the off-target impact of these very important antibiotics. We designed and executed a mutli-omics strategy centered ...
Genome On Rails
Comparative genomics approaches in microbiology now use thousands of genomes to analyze a given species in different environmental or medical contexts. By collecting and comparing these genomic sequences, many studies are focusing on the overall gene content of a species (i.e. the pan-genome) to understand their evolution in terms of core and accessory parts. Variable regions are of primary importance to understand the adaptive potential of bacteria and contain genomic regions that ar...
Deciphering the global response of human macrophages against M. tuberculosis
Human macrophages are the main cell target of Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis. Once phagocytosed, bacilli escape bactericidal functions of macrophages and they multiply inside the cell. Understanding interactions between bacilli and human phagocytes is primordial to develop new strategies to combat tuberculosis. We propose a project aiming at deciphering cell-cell communications between infected cells and non-infected cells. We will use the trans...
Re-annotation and HTseq analysis of the Sudanese L. donovani strain LdS1
The Sudanese L. donovani strain Ld1SA is the most important experimental reference strain in our field and has been used for various systems level analysis (DNAseq, RNAseq, proteomics). However, all these analyses are strongly compromised by the fact that the current L. donovani genome reference strain LdBPK is from Nepal and very different from the Sudanese isolate (only 60% of DNAseq reads can be mapped)....
Do faecal microbiome phages facilitate antibiotic resistance?
The dramatic increase in bacterial resistance to antibiotics, particularly of Gram-negative bacteria, poses an immediate threat to our health system. The main driver of this trend is the impact that antibiotics, including b-lactams, exercise on intestinal commensal flora of humans and animals by selecting resistant strains. The intestinal microbiota, with its large spectrum of bacterial populations, density and diversity, can be considered the epicentre of the emergence of resistance. The presen...
Transcriptome du fibroblaste cutané humain: une approche pré-expérimentale
Dans le contexte du LabEx Milieu Intérieur (MI) dirigé par M. Albert et L. Quintana-Murci, 300 lignées de fibroblastes cutanés ont été préparées à partir de donneurs sains stratifiés selon l’âge et le sexe. Le projet « Fibroblastes » du Labex MI mené à la plateforme d’Imagerie dynamique contribue à l’étude de la variabilité de la réponse immune de donneurs sains en analysant la réponse immune innée des fibroblastes.L’étude du transcriptome est devenue un moyen imp...
Mise a disposition d'un(e) bioinformaticien(ne) du hub pour les analyses bioinformatiques du transcriptome et de l epigenome
La PF Transcriptome et Epigenome développe des projets de séquençage à haut débit (collaboration et service) avec des équipes du Campus. Ceux-ci couvrent l'ensemble des thématiques du campus ainsi qu'une large gamme d'organismes (des virus aux mammifères). La plate-forme exerce des activités de biologie humide (construction des librairies et séquençage) et de biologie sèche (analyse bioinformatiques et statistiques). La personne mise a disposition interagira étroitement avec les au...
Horizontal gene transfer in mycobacteria
Horizontal gene transfer (HGT) is a major driving force of bacterial diversification. For mycobacteria, a special type of HGT was described in Mycobacterium smegmatis which is linked to distributive conjugal transfer (Gray et al., PLoS Biology, 2013). In the current project we are trying to reproduce the results and explore the process....
Yeast comparative genomics
A major program of evolutionary and comparative genomics of yeasts has been in progress in my laboratory for many years (see publications). In the next few months (before summer 2015) I need to finish a few comparisons about a new clade to publish as soon as possible....
N/A
N/A...
sequence conservation in the vicinity of Gli3 binding sites in the mouse genome
Gli are transcriptional regulators involved in the Shh signalling pathway. Gli3 binding sites on DNA have been defined in the mouse genome by ChIP-chip experiments (Vokes et al., 2008). We are working on the Msx transcription factor family, and have strong evidence indicative of interactions between Msx1 and Gli3 at the protein level. This might reflect in Msx1 binding to DNA in the vicinity of Gli3 binding sites. However, Msx1 binding sites are ill-defined. One stategy to confirm this hypothesi...
Pasteur International Bioresources Network (PIBnet) bioinformatics: whole-genome sequencing of microbial agents for disease surveillance, outbreak investigation, epidemiology and population biology
The PIBnet initiative is a joint effort by 15 National Reference Centers (NRC), 8 Collaborative Centers of World Health Organization, the Collection de l’Institut Pasteur & Cyanobacteria collection and the CIBU to modernize their activities, including collection management and microbial characterization approaches and technologies. Within this large concerted effort, a priority is to promote whole genome sequencing (WGS) as the major characterization approach of microbial agents for survei...
A reference panel of dengue vector genomes
Dengue prevention relies primarily on controlling populations of the main mosquito vector, Aedes aegypti, which is failing in many parts of the world because of the lack of sustained commitment of resources and ineffective implementation. Novel entomological approaches to dengue control are being developed that aim at replacing or suppressing mosquito vector populations. Insufficient genomic resources for Ae. aegypti, however, have until now impeded progress in both basic and a...
How ribosomal protein gene position impacts in the genome evolution during a long term evolution experiment.
Increasing evidence indicates that nucleoid spatiotemporal organization is crucial for bacterial physiology since these microorganism lack a compartmentalized nucleus. However, it is still unclear how gene order within the chromosome can influence cell physiology. In silico approaches have shown that genes involved in transcription and translation processes, in particular ribosomal protein (RP) genes, tend to be located near the replication origin (oriC) in fast-growing bacteri...
Regulation by phase variation and attenuation: looking for leader peptides containing repeats in the intergenic regions of streptococcal genomes
We have described recently a novel mechanism of regulation combining phase variation and attenuation of two pilus operons in Streptococcus gallolyticus . Phase variation occurs by single-strand mispairing during replication due to the presence of repeats in the leader peptide located immediately upstream of the pilus operon. We wonder if the same mechanism is applicable to other bacterial genes....
MicrocystOmics
Les cyanobactéries sont des microorganismes qui prolifèrent dans de nombreux plans d’eau et perturbent leurs fonctionnements et leurs usages car elles sont capables de produire des toxines dangereuses pour la santé humaine et animale. Si la réglementation sanitaire est basée, pour l’instant, sur la surveillance d’une seule toxine, il est désormais connu que ces microorganismes sont capables d’en synthétiser un grand nombre qu’il conviendrait de mieux prendre en compte dans le fu...
- Christophe Bécavin
- Rachel Legendre
- Hugo Varet + 1 operator
Updating the Topo IB gene tree
DNA topoisomerase IB (Topo IB) enzymes are ubiquitous in eukaryotes, where they represent the major DNA topoisomerase I activity. However, Topo IB sequences are also found in other phyla, such as archaea and bacteria, as well as viruses. Given the large amount of sequenced data available in public databases, this project aims to infer a robust Topo IB gene tree based on a representative set of homologous sequences gathered from a large taxonomic sample....
Assemblage de novo d'une souche d'E. coli
Assemblage de novo d'une souche bactérienne afin de pourvoir la soumettre dans une plateforme d'annotation....
A program to identify integrons, attC sites and gene cassettes
Integrons drive the spread of antibiotic resistance genes in bacterial populations. While their role is widely known (integron+antibiotic+resistance in PubMed gives > 1700 hits), there was no software available to identify integrons and their different components. We have made a script (in Python) which annotates DNA sequences (with prodigal), then identifies the integrase of the integron (using hmm protein profiles), searches attC sites (using covariance models from structurally annotated multi...
Identification of Transcription Start Sites and small RNAs in Leptospira interrogans by transcriptome analysis
Leptospiral promoter regions are poorly characterized: experimentally proven transcription factor binding sites have not been described in the literature and promoter prediction algorithms and E. coli consensus sequences of DNA motifs are not appropriate for Leptospira. Identification of Transcription Start Sites (TSS) and promoters on a global scale will provide essential information on DNA motifs that are targets of RNA polymerases, sigma factors and transcription factors. RN...
Role of SUMO, a new epigenetic mark, in stress response
The post-translational modification by SUMO is an essential regulatory mechanism of protein function that is involved in most challenges faced by eukaryotic cells. Gene expression is particularly regulated by sumoylation as many SUMO substrates are transcription factors and chromatin-associated proteins, including histones. The emerging paradigm for the proposed work is that sumoylation controls multiple aspects of chromatin structure and function in response to external cues. According to this ...
INNOV DIAG HPV
Molecular markers of cervix lesions linked to HPV infections....
Influence of chromatin dynamics on genomic stability during replication
Genomic DNA is hierarchically packed within the living cells and genome duplication requires the concerted effort of many thousands of individual replication units. As such, to ensure the integrity of transmission of the genetic information, both eukaryotes and prokaryotes have evolved sophisticated mechanisms to monitor DNA replication. Some of these mechanisms aim to maintain both a temporal and a spatial organization of the replication program, leading to multiple replication time regions and...
Transcriptome analyis of two human T cell subsets
The summary is below. I would prefer to keep it confidential except the tittle...
a web interface for MacSyFinder (a tool to detect macromolecular systems in genomes).
The tool MacSyFinder and the viewer MacSyView provide a framework to model macromolecular systems in genomes, allow their precise detection, and their visualisation in genomic context. These tools were co-developped by Sophie Abby, Bertrand Néron, Hervé Ménager, Marie Touchon and Eduardo Rocha. MacSyFinder has been the subject of a demand for a US patent by the Institut Pasteur. The aim of the project is to increase the value and accessibility of these tools by designing a web interface, a...
Analysis of host epitranscriptional modifications upon colonisation with commensals and infection by bacterial pathogens
The colonisation of the murine gut by commensal bacteria has been shown to profoundly influence the host physiology. We would like to investigate if these effects are in part mediated by changes in epitranscriptomics, i.e. mRNA modifications influencing the stability and degradation of mRNA (Dominissini et al. Cell 2012, Meyer et al. Nature 2012). To this end, we aim to investigate the levels of the m6A modification of mRNA and differentially methylated targets in organs derived from mice with a...
Deconvolution of synthetic homologous chromosomes in 3D
Meiosis is the specialized, highly regulated process at the basis of the sexual reproduction of eukaryotes. During this process, a diploid cell undergoes a single round of DNA replication and two successive rounds of chromosome segregation, halving the chromosome set to generate four haploid products (gametes). Homologous (i.e. paternal and maternal) chromosomes during the prophase of the first division of meiosis undergo a highly regulated succession of events that include recognition, pairing,...
Analyse de données de microarray
Grâce à la plateforme PF2 à Pasteur, nous avons réalisé une étude de microarray ( Affymetrix Genechip Mouse Gene 2.0 ST Array) avec les fibroblastes de souris. Pourriez vous SVP nous aider à analyser ces données?...
Characterization of an unusual Leishmania major HSP70-related protein
WYSIWYG editor...
Single cell gene expression profiling of HIV-specific CD8+ T cells associated with HIV control
Controlling virus replication by generating a strong CD8+ T cell response against HIV is one of the major goals in the development of an effective HIV vaccine candidate. Indeed, during the chronic phase of infection, HIV-specific CD8+ T cells were shown to have impaired functionality and fail to control viral replication. Understanding the profile of CD8+ T cells able to efficiently tackle HIV is therefore much needed. HIV controllers (HIC) are individuals who control viremia without antiretrovi...
Implementation of a statistical tool for HDX-MS data analyses
Hydrogen deuterium exchange detected by mass spectrometry (HDX-MS) is a powerful technique to probe the conformation and dynamics of proteins. Over the past 10 years, the HDX-MS workflow has been optimized and automatized leading to a rapid expansion of the technology in both academic lab and pharmaceutical companies. Thanks to these improvements, modern HDX-MS can be applied to investigate more complex biological systems, including large protein complexes and membrane proteins. However, the hig...
Analyse de séquence 16S
To perform assignment of 16S sequences to bacterial genera and statistical analysis of variations of bacterial populations collected from mice feces...
Analyse de données de miRNA
Recherche de cible pour des miRNAs chez l'Humain....
Methods to identify and characterize orthologs of genes encoding small proteins
We wish to investigate the extent of conservation and prevalence of small orfs of unknown function expressed in stationary phase of growth in Salmonella...
Analyses of SNP diversity of Legionella pneumophila strains
Legionella pneumophila is from a genomic point of view a very diverse species, however, only few clones are responsible for over 50% of all human disease cases. Thus we aim to understand the evolution and emergence of these 5 major disease related clones. We have sequenced a large number L. pneumophila strains belonging to these clones and are undertaking comparative and phylogenetic genome analyses....
Interactive web interfaces and Analysis Tools of Bacterial NGS data for Postgenomics Life Scientist
Improvement of two existing tools, COV2HTML (published in 2014) and SEQ2HTML (private), and transform two scripts into interactive web interfaces addressed to biologists. ...
Genomic analyses of E. coli strains
We are examining differences within the genomes of E. coli strains....
Molecular analysis of muscle stem cells
Skeletal muscle stem cells constitute a population of cells with heterogeneous properties. Interestingly, muscle stem cells have a remarkable capacity to regenerate muscle fibres after regeneration. We are performing a molecular analysis of these stem cells....
Transfert annotations
Transfert des annotations d'un fichier genbank sur une séquence fasta ayant une région de 183 kb inversée par rapport à la séquence parentale...
Identification of new cellular parameters involved in HIV-1 integration selectivity
HIV-1 replication requires the integration of the viral genome into the cell genome. A viral-encoded enzyme, integrase (IN), performs this critical step of infection and is a promising target for anti-viral therapeutics. If the catalytic properties of INs are well characterized, the mechanisms responsible for their site selectivity are still under investigation. Several cellular proteins, such as the LEDFGF/p75 transcription co-activator, the RNA polymerase II machinery, nuclear pore proteins an...
Formatage et soumission de données à l'EBI
Le génome de Cryptococcus neoformans a été réannoté grâce à des données RNA-seq. Ces nouvelles annotations doivent être soumises dans les banques publiques....
Détection de variants dans des données NGS (miSeq) de phage
The goal of this project is to set sequence analysis tools to evaluate the frequency of mutations within a pool of bacteriophage genomes sequenced by NGS....
Whole-genome sequencing of microbial agents for disease surveillance, outbreak investigation, epidemiology and population biology
The PIBnet initiative is a joint effort by the above laboratories to modernize their activities, including collection management and microbial characterization approaches and technologies. Within this large concerted effort, a priority is to promote WGS as the major characterization approach of microbial agents for surveillance and outbreak investigation. Our ambition is to have shifted to WGS as a routine strain characterization method for epidemiological surveillance and outbreak investigatio...
Fast and accurate implementation of the raw read coverage homogenization technique
When dealing with high depth read data, a simple way to associate accurate analyses to moderate computational resources is to extract a subset of raw reads that allows observing both homogeneous and moderate coverage depth. Unfortunately, current implementations are often unexpectedly slow and require many significant pre-processing of large files to be used in practice. I...
Systems wide analysis of amastigote and promastigote stages of Leishmania donovani
The aim of the project is to create a viewer that will help visualisation and correlation between genomic, transcriptomic, proteomic and metabolomic data generated by the comparison of amastigote and promastigote stages of the Leishmania donovani parasite....
Study of lncRNAs in Cryptococcus neoformans
The recent analysis of the Cryptococcus neoformans transcriptomes revealed the presence of thousands of lncRNAs. In these yeasts, different types of lncRNAs seem to exist. The ones that are antisense of coding genes (the NATs), the ones that are located between coding genes (the lincRNAs) and some others that seem to result from alternative transcription start site selection. We identified growth conditions under which the expression of some of them is regulated. We have also identified some g...
gRNA library design
We have recently identified around 500 long non-coding RNAs that follow a very precise expression pattern in undifferentiated mouse Embryonic Stem cells. In order to assess if any of those molecules are functionally relevant for the biology of ES cells we will perform a functional screening based on the CRISPR technology. We plan to use a modified version of the CRISPR-CAS9 technology, the CRISPRon system, in which (i) the guide-RNAs (gRNAs) will target the promoters of our candidate lncRNAs (at...
Novel regulators of cell wall maintenance in Aspergillus fumigatus
The increased incidences of invasive fungal infections coupled with the paucity of available antifungal drugs for treatment have driven the search for novel agents with unique fungal targets. Studies ...
Host microbiota modification by the pathogen Listeria monocytogenes
Listeria monocytogenes is a gram positive facultative intracellular foodborne bacterium responsible for serious clinical manifestations including febrile gastroenteritis, meningitis, encephalitis and maternofetal infections in humans and livestock. Intestinal microbiota plays fundamental roles in the resistance to foodborne infections. Intestinal microbiota commensals protect against pathogens by direct antimicrobial activity through production of bacteriocins, competition for nutrients o...
Mapping of research themes and fields of expertise available in the Institut Pasteur international Network
Using data extracted from Pubmed, we would like to develop a tool for systematic analysis of research themes and fields of expertise available in the Institut Pasteur International Network (IPIN). The tool would be available to the Pasteur community and could be questioned using search terms in Pubmed, identifying articles involving research teams from IPIN and displaying the name of authors, research units, and location in a visual format. We hope this tool would enable researchers to ident...
Development of analysis tools for mate-paired data.
The developed tool will allow to retrieve usually filtered information in experiments that generate mate-paired sequences....
Assembly of 3 Bacillus strains
Continuous updating of the genome sequence of Bacillus subtilis, the model of the Firmicutes, is a basic requirement needed by the biology community. In this work new genomic objects have been included (toxin/antitoxin genes and small RNA genes) and the metabolic network has been entirely updated. The curated view of the validated metabolic pathways present in the organism as of 2012 shows several significant differences from pathways present in the other bacterial reference, Escherichia coli: v...
- Claudia Chica
- Alexis Criscuolo
- Varun Khanna + 3 operators
Gene regulation in yeast quiescence
In wild life, yeast cells are able to survive in severe conditions, without nutriment for a long period of time because the cell is able to enter in stationary phase. During this phase, the cell can transform varied sources of energy and pause its growth to preserve the cells from death. It is known that most of genes are downregulated in stationary phase and the cell activity is globally reduced to its strict minimum, while a subset of “specialized” genes is induced to promote survival in e...
viral evolution around Ebola Treatment Centre in Macenta and according to disease outcomes
The 2013-2015 Ebola virus disease epidemic is the largest outbreak so far described with 27 305 cases and 11 169 deaths. The virus spread by human to human contact throughout Western Africa and never before has a variant been transmitted for such a sustained period of time. Ebola virus are RNA virus so as other RNA viruses they could accumulate mutations during evolution. Therefore it is an emergency to monitor viral changes and adaptation within and between individuals in order to help research...
Transcriptome of Human sperm
We search for the expressed transcript in mature normal sperm as compared to the infertil one....
Systems Biology Data Management and Analysis Platform (SYSMAP)
Most of the national and international projects performed between our lab and the GFMI unit (Anavaj Sakuntabhai) are driven by data collected at different (molecular/cellular/clinical) levels. The increased use/reuse of multiple data sources, large-scale technologies and increasing cohort sizes make state-of-the-art data management and analysis on a project-by-project basis very labor-intensive. To ensure efficiency and quality of our data-rich research, we propose the creation of a Systems Bio...
Impact des facteurs épidemiologiques et strategiques sur l'incidence du paludisme à Thiès
L’objectif de cette thèse s’inscrit dans le but commun aux pays d’Afriques sub-saharienne celui des évaluations des stratégies thérapeutiques et des choix des politiques de santé publique dans la lutte contre le poids en terme de morbi-mortalité qu’ y représente le paludisme à plasmodium falciparum notamment chez l’ enfants . Il concerne la méthode d’évaluation globale de l’étude de l’impact des facteurs épidémiologiques et stratégiques sur l’incidence du paludis...
HIghthroughput CRISPR-Cas9 screen in bacteria
CRISPR-Cas9 tools have recently emerged as a very powerful way to edit genomes and control gene expression. The Cas9 protein is an endonuclease that can be guided by a small guide RNA (gRNA) to any target DNA sequence of choice. This feature has enabled the construction of gRNA libraries to perform genome-wide CRISPR-Cas9 functional screens. Such screens have notably been used to identify factors involved in drug and toxin resistance in human cells. We are now in the process of developing such a...
MacSyFinder development: models data structure
Modification of MacSyFinder models and profiles data structure to facilitate models distribution, and integration in the Mobyle platform. This consists in organizing the way XML models and HMM profiles of given system or set of systems in order to allow running the detection of all the macromolecular systems in a given folder. This will also ensure that the profiles are always distributed with the appropriate definitions of the systems, and thus avoid collisions of profiles name....
Genome-wide replication lanscape of Candida glabrata
Background: The opportunistic pathogen Candida glabrata is a member of the Saccharomycetaceae yeasts. Like its close relative Saccharomyces cerevisiae, it underwent a whole-genome duplication followed by an extensive loss of genes. Its genome contains a large number of very long tandem repeats, called Megasatellites. In order to determine the whole replication program of C. glabrata genome and its general chromosomal organization, we used deep-sequencing and Chromosome Conformation Capture (3C) ...
Phylogenetic analysis of the Leishmania HSP70 protein family
Across bacterial, archaeal and eukaryotic kingdoms, heat shock proteins (HSPs) are defined as a class of highly conserved chaperone proteins that are rapidly induced in response to temperature increase through dedicated heat shock transcription factors. While this transcriptional response governs cellular adaptation of fungal, plant and animal cells to thermic shock and other forms of stress, early-branching eukaryotes of the kinetoplastid order, including trypanosomatid parasites, lack classica...
Characterisation of skeletal muscle stem cell properties in distinct physiological states
Stem cells are defined by their is their capacity for self-renewal and differentiation. Some adult tissues maintain a reservoir of stem cells, that generally reside within specialized microenvironments, known as stem cell niches, that regulate their behaviour. Skeletal muscle stem (satellite) cells are quiescent in homeostatic conditions in adults, and they are activated after muscle injury, when they re-enter the cell cycle, proliferate and differentiate into myoblasts, which will then fuse to ...
search for transcrition factors upregulating Tgfb1 expression in FHL2-/- cells
We observed that Tgfb1 is upregulated at the transcription level in cells deficient for the four and a half LIM-only protein 2 (FHL2). The upregulation of Tgfb1 leads to increased liver and kidney fibrogenesis in FHL2-/- mice. We have carried out microarray analysis with mouse embryonic fibroblasts derived from FHL2-/- embryos. We would like to have help for the analysis of our microarray data to identify the transcription factors that would be responsible for the upregulation of Tgfb1 expressio...
Characterization of microevolution in Candida albicans isolates
Candida albicans is responsible for the majority of life-threatening fungal infections occurring in hospitalized patients and is also the most frequently isolated fungal commensal of humans. Microevolution of C. albicans isolates has been observed in a number of instances, being in particular characterized by loss-of-heterozygosity events. Yet, most studies that have investigated such microevolutions have not used whole-genome sequencing. In this project, we aim to characterize C. albicans micro...
Candida albicans population genomics
Candida albicans is responsible for the majority of life-threatening fungal infections occurring in hospitalized patients and is also the most frequently isolated fungal commensal of humans. The C. albicans population includes at least 18 phylogenetic groups (or clades). Specific phenotypes can distinguish isolates within a given clade from those in other clades and yet, the relationships between C. albicans natural genetic and phenotypic diversities have not been explored in depth. We have sequ...
Evolutionary relationships between giant viruses and eukaryotes
The phylogenetic position and status of “giant viruses”, formerly called NucleoCytoplasmic Large DNA viruses (NCLDV) or putative order Megavirales, are controversial. Many preliminary phylogenetic analyses have been published, but their presentations are usually highly biased by the prejudice of the authors concerning the nature of giant viruses. Our own preliminary analyses suggest that giant viruses are indeed ancient (they predate the last universal eukaryotic ancestor) and have possibly ...
An automatic pipeline to call SNPs from RNA-seq reads
Dengue is an arthropod-borne viral disease caused by dengue virus (DENV), which is transmitted by Aedes mosquitoes. Recent studies estimate that 100 million cases occur annually worldwide, making dengue the most prevalent mosquito-borne viral disease of human beings. DENV transmission results from interactions between humans, mosquitoes, viruses and their environment. If the human immune response against DENV is well studied, there are knowledge gaps in understanding how mosquitoes and DENV inte...
développement d'un logiciel danalyse sur la base de spade et visne
Nous recherchons un logiciel basé ou pas sur spade qui tourne sous R qui permet de faire une analyse des fichiers de cytométrie de type FCS par clustering multiparamétrique. nous serions également intéressé par visne également. les fichiers peuvent être transformé en CSV Il existe un logiciel commercial Cytobank mais qui ne rempli pas toute les fonctions souhaité....
Regulation of HIV replication by cellular DNA topology
HIV-1 replication requires the integration of the viral genome into the cell genome. A viral-encoded enzyme, integrase (IN), performs this critical step of infection and is a promising target for anti-viral therapeutics. If the catalytic properties of INs are well characterized, the mechanisms responsible for their site selectivity are still under investigation. Several cellular proteins, such as the LEDFGF/p75 transcription regulator, the RNA polymerase II machinery, nuclear pore proteins and s...
Genomic approach for the identification of new targets of antimycobacterial drugs
Several mycobacterial species have been used for the screening of chemical libraries with the aim of avoiding natural resistance mechanisms developed by specific species. In this way, different compounds with antibacterial activity have been identified. Mutants resistant to each compound have been isolated and their genomes have been sequenced. The comparison of these sequences with the wild type strain genome will allow us to identify the targets for the antibacterial activity and the mechanism...
Mapping the cell surface signature of the developing mouse heart
Cell surface protein signatures have been successful to discriminate hematopoietic progenitor populations allowing major advances in understanding blood cell production, to define pathways in hematologic malignancies and to foster new therapeutic approaches. Limited knowledge on the phenotype of cells that participate in heart formation impairs our understanding of progenitors of the cardiac cell lineages and their eventual persistence in the adult organ. As a consequence, therapies to restore ...
Sequence alignment – implement algorithm in C
The CRISPR/Cas9 technology is a recent breakthrough in rapid genetic editing. A major part of getting the technology to work is the proper design of a guide RNA that will help Cas9 target specific genomic sequences. The design of this guide RNA must take into account all possible matches along an organism’s genome with as little as 50% similarity. Such a high toleration for error means that current alignment algorithms are not well suited to the task. This issue leads to suboptimal guide RNA d...
Image-based siRNA and drug screens of infection by the pathogen Listeria monocytogenes
In the context of the swiss consortion InfectX (www.infectx.ch), we performed siRNA and drug screens to investigate the invasion of host cells by the bacterial pathogen Listeria monocytogenes. As a primary readout for infection we detected by fluorescence microscopy the presence of the bacterially-secreted protein InlC, which accumulates in the cytoplasm of infected cells (Kühbacher et al. 2013). A first manuscript concerning the analysis of a kinome-wide siRNA library and a drug library has be...
Linking Phenotype to genotype in C. neoformans clinical isolates
Cryptococcus neoformans is a pathogenic yeasts that infect mostly immunocompromised people. The strain H99 belongs to the C. neoformans variety grubii group. This is the reference strain that have already been sequenced. A project initiated by the Broad Institute aims at analysing the genome of about 300 clinical isolates including 28 of our French isolates. Part of our French isolates have been screened in terms of interaction with macrophages (774). Huge variations in terms of phagocytosis ...
