BISTRO
Beautiful Interface and System To Report and Organize
#19216 : Evolution towards bipartite genome - core genes distribution in monochromosomal and bichromosomal Paracoccus species
The genus Paracoccus (Alphaproteobacteria) includes bacteria carrying genomes of very different structure - from unichromosomal strains containing no plasmids (P. suum), through strains possesing multiple extrachromosomal replicons of medium size (hundreds kb) and different nature (megaplasmids and chromids) (e.g. P. aminophilus, P. yeei or P. marcusii), to strains having a large well-constituted chromosome 2 (a chromid of over 1.5 Mb with high density of housekeeping genes), which are found in ...
#19215 : Red Cross health workers and the continuity of care in the COVID-19 pandemic: A mixed methods operational approach
Voluntary organizations provide essential support to vulnerable populations and front-line health responders to the COVID-19 pandemic. The French Red Cross (FRC) is prominent among organizations offering health and support services in the current crisis. Comprised primarily of lay volunteers and some trained health workers, FRC volunteers in the Paris (France) region have faced challenges in adapting to pandemic conditions, working with sick and vulnerable populations, managing limited resources...
#19214 : The mode of replication of repABC replicons (Alphaproteobacteria)
RepABC replicons consist one of the most important groups of extrachromosomal replicons in Alphaproteobacteria, which includes numerous plasmids (e.g. pTi of Agrobacterium), megaplasmids (e.g. pSymA of Sinorhizobium) and chromids (e.g. chromosome 2 of Brucella). Recently, we have experimentally demonstrated that within this family some replicons replicate unidirectionally and others bidirectionally. This project aims to identification of phylogenetical patterns of distribution of these two repli...
#19207 : Etude de la réponse immunitaire néonatale dans la coqueluche maligne : approche transcriptomique
La coqueluche est une infection respiratoire communautaire causée par la bactérie Bordetella pertussis (Bp). Elle est à l’origine d’un nombre important d’hospitalisations malgré une couverture vaccinale élevée, et est responsable d’une mortalité conséquente. La forme la plus sévère de cette maladie, la coqueluche maligne, est observée chez des nourrissons âgés de moins de 3 mois et est caractérisée par une détresse respiratoire aigüe, une défaillance multiviscérale...
#19152 : Detection of newly produced NIRVS in mosquito persistently infected cells
Persistent viral infections in mosquitoes require equilibrium between viral replication and efficient antiviral defenses. Arboviruses are able to counteract immune defenses and especially, the RNAi system. Production of DNA forms from several non-retroviral RNA viruses (vDNA) has been found to promote persistent infections and prevent lethal acute infections in mosquitoes and cell cultures. In vitro, vDNA was detected at the early stage of infection (24 hours post-infection for dengue virus). vD...
#19137 : User experience design for Oncodash
Oncodash is an open-source software developed within the DECIDER H2020 project, which aims at improving clinical decisions via integrating multiple data to overcome chemotherapy resistance in high-grade serous ovarian cancer. The corresponding DECIDER workpackage is led by Johann Dreo and Benno Schwikowski. The current state of the software can be checked at: https://github.com/oncodash/oncodash...
#19128 : Evaluation of a novel mouse model for Primary Antibody Deficiency (PAD)
Previous animal models of Primary Antibody Deficiency (PAD) display severe dysbiosis and gut inflammation, which makes them incompatible to study a wide spectrum of PAD (e.g., most IgAD subjects display only mild dysbiosis and are asymptomatic). We would like to evaluate a novel mouse model of PAD and then perform microbiome transplant and IgA supplementation. The first objective is to evaluate the causal role of the microbiome in mediating PAD-associated disease. Our second objective is to appl...
#19121 : Understanding the mode of action of epigenetic inhibitors active against Plasmodium falciparum
We are working on malaria drug discovery. In an attempt to understand the mode of action of epigenetic inhibitors active against Plasmodium falciparum, we culture the parasite under drug pressure to induce drug resistance, along with a control treated in the same conditions with the solvent only. We then clone resistant and control parasite lines and sequence their genomes to compare them to try to understand which gene is responsible for the resistance and thus may constitute the inhibitor's ta...
#19120 : Deciphering mutation signatures on hepatitis B virus genome
According to the WHO, the Hepatitis B virus (HBV) infects chronically 295 million persons. After several decades, persistently infected patients become at risk to develop liver cirrhosis and/or liver cancer (hepatocellular carcinoma, HCC). Each year around one million persons die from these two complications directly triggered by HBV. In the course of infection, the HBV DNA genome accumulates mutations that become progressively dominant. Some of the recurrent mutations are suspected to play a...
#19119 : Comparative genomics analysis of cyclic-di-GMP metabolism across the Leptospira genus
Finely tuned sensory systems enable bacteria to sense and respond to fluctuating environments, coordinating adaptive changes in metabolic pathways and physiological outputs. For pathogenic Leptospira, signaling pathways allow a timely expression of virulence factors during the successive steps of infection of a mammal host. As the bacteria is excreted by its host, signaling pathways enable switching the expression towards factors promoting survival in the environment. A unifying theme across bac...
#19102 : Exploring pathogenic mechanisms of chronic inflammatory disease: unresolved issues in IL-23/IL-17 biology
Chronic inflammatory diseases (CID) are clinically heterogeneous conditions that share common inflammatory pathways and derive from aberrant immune responses. Genome-wide association studies (GWAS) demonstrated that Th17 cells play a pivotal role in the pathogenesis of these diseases and several loci involved in the IL-23/IL-17 are associated with the CID (IL23R, IL12B, IL6R, IL1R2, RORC, RUNX3, TYK2, JAK2, CARD9). IL-23 is important for the expansion and the functional activity of the Th17 cell...
#19089 : Research of homopolymers in the integron integrase genes
Research of homopolymers in the integron integrase genes...
#19086 : FLAVIMMUNITY
FlavImmunity is an international project aiming to study the immune response developed after yellow fever vaccination....
#19084 : Modelization of the timing of abscission
Cytokinesis is the last step of cell division and leads to the physical separation of the daughter cells. The purpose of this project is to infer the timing of abscission in various cell types by using few microscopic images of live cells and fluorescent markers....
#19082 : fliC locus of Y. pestis
The fliC locus codes for the FliC protein, the flagellin molecule that constitutes the flagellar filament of motile bacteria, like Y. pseudotuberculosis. Until now, it was commonly accepted that transcription of this locus was completely repressed in the non-motile Yersinia pestis (a recent clone of Y. pseudotuberculosis, which still harbors flagellar genes), but by transcriptomics analysis we observed that it was actually active. Even more, we showed that deletion of the fliC locus in Y. pestis...
#18716 : Better characterization of long chimeric virus-human reads after target enrichment on integrated viral genomes.
Since the advent of 3rd generation sequencing technologies, the application of long-read sequencing has had many applications in the study of infectious diseases. There is one area where these technological improvements can have a considerable impact on a better understanding of the disease, namely in virus-induced cancers. Indeed, in most cases, the viral genome integrates into the host genome and during this process may also induce alterations in the host genome at the site of integration (del...
#18714 : Genetic diversity of arbovirus populations in Aedes aegypti mosquitoes from Colombia
Several arboviruses have emerged and/or reemerged in the New World in the past decades. While yellow fever and dengue are historical diseases which continue to cause deadly epidemics, Zika and chikungunya have recently invaded the South American continent, causing great concern. In Colombia, Aedes aegypti is the vector of most of human arboviruses. We collected Ae. aegypti eggs in Medellin in Colombia in 2020 and infected adults with dengue (DENV), chikungunya (CHIKV), yellow fever (YFV) and Zik...
#17991 : Genetic diversity of yellow fever virus populations in mosquitoes
Yellow fever (YF) is a fatal hemorrhagic disease caused by an arbovirus, Yellow Fever Virus (YFV) transmitted by the Aedes aegypti mosquito vector. YFV is currently endemic in Africa (5 strains) and South America (2 strains), and although an effective vaccine is available, YFV remains a major public health issue. Native from Africa, YFV was transported to South America and the Caribbean during the slave trade (15th to 19th century) and caused devastating outbreaks. After two centuries of outbrea...
#17976 : Fast and accurate identification of the medoid of a set of genomes
Because of the fast-growing number of assembled genomes available in the public repositories (GenBank/RefSeq), it is now quite common to end up with many genome assemblies that belong to the same species. In this current context, determining the type strain/species of any new species/genus requires to identify the representive one(s) within a large collection of genomes. The medoid of a genome collection being the one(s) whose sum of distances to all other genomes is minimal, it is an ex...
#17970 : Identification of non-coding RNAs regulated by oxidants in pathogenic Leptospira
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 estimated annually in the word, with 10% of mortality. Patho...
#17965 : Evaluation in cellulo of the impact of insecticide usage on arbovirus population
The recent propagation of resistance mechanisms to insecticides constitutes a major challenge in the fight against the transmission of vector-borne diseases. Even though alternatives are being explored in mosquitoes, there are few studies focusing on the role that these molecules could have or play in the transmission of arboviruses. Using an in cellulo model, this project aims to determine the impact that an insecticide selection can have on an infection caused by the chikungunya virus....
#17962 : Measles virus type 1 infection disturbs the mitochondrial network leading to type I interferon production through the RNA polymerase III/RIG-I pathway
Measles virus (MeV) impairs the mitochondrial network. This leads to the fusion of mitochondria and simultaneous release of mitochondrial DNA (mtDNA). We have shown that released mtDNA is recognized as a danger signal, capable of stimulating signaling pathways and inducing the production of pro-inflammatory cytokines. The expression of human cytidine deaminase APOBEC3A is highly upregulated by interferon responses. This enzyme catalyzes the deamination of cytidine to uridine in single-stranded m...
#17940 : Analysis of the molecular pathways induced by the activation of the Nod2 receptor by MDP in hypothalamic neurons
Nod2 is expressed on brain neurons, however the downstream effects of its activation by its ligand MDP are not know. We used RNAseq strategy to answer this question...
#17921 : Viral metagenomic in noctule bats from East Europe
The objective of this project is to study the virome present in noctule bats from East Europe, in order to identify potential (re) emerging zoonotic viruses....
#17917 : Viral metagenomic in Chinese bats and their associated ectoparasites.
The objective of this project is to study the virome present in specific bat colonies in China and their associated ectoparasites, in order to identify potential (re) emerging zoonotic viruses and to elucidate their transmission route, especially as putative arboviruses....
#17905 : PacBio sequencing analysis of DM1 cells
Myotonic dystrophy type 1 (DM1 or Steinert disease) is a monogenic neurodegenerative disorder due to the expansion of a CTG trinucleotide repeat in the 3' UTR of the DMPK gene on chromosome 19. We developed a strategy to induce a DNA double-strand break (DSB) within the expanded repeat in order to contract it below the pathological range in humans. This approach was successful in yeast and mouse cells and we are now trying to apply it to human cells from a patient affected by DM1. This patient w...
#17897 : Effect of Chlamydia trachomatis infection on histone methylation and consequences
We observed that Chlamydia trachomatis infection results in deep changes in the histone methylation profile of the infected cells....
#17896 : Quick phage data mining
We are studying a specific genomic signature and would like to evaluate how frequent is this signature in phage genomes....
#17884 : Identification of factors influencing the activity of bacteriophage within the gut of mammals
We aim to characterise the transcriptome of OMM12 mice under different experimental conditions...
#17865 : Monitoring tool for scientist who have received MAASCC career guidance
Monitoring tool for scientist who have received MAASCC career guidance...
#17789 : Study of the role of cyclic dimeric guanosine mono-phosphate (c-di-GMP) in the regulation of virulence and biofilm formation in Leptospira interrogans
Leptospirosis is a re-emerging zoonosis that affects more than one million people and causes nearly 60,000 deaths per year worldwide. This disease transmitted to humans via an environment contaminated by bacteria of the genus Leptospira has a record incidence in Oceania. Pathogenic leptospires are able to survive for several weeks in the environment. The production of a biofilm allows them to efficiently resist to hostile conditions and would explain their persistence in the environment. Our rec...
#17778 : Codon Usage Bias Analysis in Vibrio
Vibrio cholerae has a multipartite genome. This project aims to analyze the codon usage bias of each replicon to see if there is a difference....
#17746 : Support technique - Cours de Phylogenie
Installation logiciels sur machine virtuelle linux deployée sur 16 postes au centre des enseignements (salle 5 )...
#17745 : A genome-wide RNAi screening for mitochondrial fission factors
Mitochondria are dynamic organelles that undergo constant morphological changes, resulting from fusion and fission events. Mitochondrial fission is crucial for mitochondrial function, apoptosis, mitophagy, and mitochondrial segregation during mitosis. While core mitochondrial fission factors have been elucidated and characterized, it is unclear if additional molecules participate or are main players of the fission process. To solve this question, we setup a genome wide, high content imaging (HCI...
#17744 : Estimation of the impact of differential apoptotic rate on local clone size
We have performed a systemic characterisation of apoptosis distribution and clone dynamics in the Drosophila wing imaginal disc. Surprisingly, we outlined a systematic spatial bias in the rate of apoptosis with regions shoing high rates of apoptosis which correlate with high probability of clone disappearance and small clone size. We would like to formulate analytically the prediction of local clone size assuming a homogenous proliferation rate and knowing spatial differences in clone disappeara...
#17743 : Comparative analysis of choanoflagellate proteomic data
Proteomes of different cellular compartments of choanoflagellates will be compared to omic datasets from other species to gain insights into the evolution of animal cellular phenotypes....
#17724 : Gene conversion and allelic selection drives L. donovani genomic adaptation in experimental Sand fly infection
Leishmania genomic adaptation during sand fly infection is only poorly understood. In particular, the possibility of allelic selection in a given parasite population inside the insect vector has not been investigated, even though sexual recombination and the possibly of self-sex (selfing) can change allele frequencies and thus may be relevant for parasite transmission and virulence. We investigate this important open question conducting experimental sand fly infection with bona fide amastigotes ...
#17689 : Centrosome and basal body function in human parasites
Centrosomes are the main microtubule organizing center of eukaryotic cells with critical roles in cell division, polarity, signaling and structure. In most cells, one or both centrioles act as basal body (BB), nucleating microtubules to form cilia or flagella, sensory and motile organelles of vital importance for a wide range of biological functions. Notorious deadly diseases such as cancer, microcephaly and ciliopathies correlate with dysregulation in the number and/or structure of the centroso...
#17687 : Early life imprinting of the immune system by the gut microbiota
The weaning reaction is a robust intestinal immune response that is induced by the expansion of the symbiotic microbiota during food diversification from milk to solid food. This weaning reaction is critical in setting the reactivity of the immune system in the long term to confer protection against inflammatory pathology in adulthood. With the aim to identify the key players in mediating this protective immunological imprinting, this project focuses on elucidating the role of myeloid cells and ...
#17660 : HKA: systemic analysis of two-component signalling
Bacteria use two-component systems (TCS) to sense and adapt to their environment. The aim of this project is to characterize the regulatory network of each of the 20 TCS in the neonatal pathogen Streptococcus agalactiae....
#17619 : CORSER-4 Cohort Study: Assessment of the humoral immune response to COVID-19 vaccination in each subpopulation defined by type of vaccination regimen, at 1-3-6-12-24 months
Vaccines against COVID-19 have been developed for use as homologous two-dose regimens and several of them have demonstrated efficacy. There is limited data on the clinical and the immune response induced by heterologous vaccination regimens (HVR) using alternate vaccine modalities. CORSER-4 is a Viro-Immunology cohort promoted by the Institut Pasteur that will follow-up subjects from the time they receive a prime vaccine dose or a boosting dose. We determined subjects sub-groups of interest def...
#17594 : An online database of RNA-small molecules complexes for rational drug design
The majority of approved drugs target proteins, which are encoded in a very small fraction of the human genome. When a pathology is associated with so-called undruggable proteins, an alternative strategy should be sought. In the last twenty years, non-coding RNA molecules have been shown to perform a variety of crucial biological functions, including regulating gene expression, protecting chromosomes from foreign nucleic acids, and guiding telomers synthesis. In this context, targeting either mR...
#17584 : Clinical and biological characterisation of auto-antibodies to the nicotinic receptors in major psychiatric disorder patient
In recent years, immune dysfunctions, including auto-immune mechanisms and peripheral inflammation, have been clearly associated with severe neuropsychiatric disorders like bipolar disorders (BD) and schizophrenia (SZ). These findings are supported by an extensive litterature highlighting a higher risk to develop neuropsychiatric disorders in patients suffering from auto-immune diseases and also the presence of low-grade inflammation and abnormal immunoglobulin rates in patients with psychosis. ...
#17578 : Regulation of IL23R expression
Chronic inflammatory diseases (CID) are clinically heterogeneous conditions that share common inflammatory pathways and derive from aberrant immune responses. Genome-wide association studies (GWAS), together with mouse models of autoimmune disease, demonstrated the implication of the IL-23 cytokine pathway in several CID. The overall goal of our work is to improve our understanding of the role of IL-23 in the pathophysiology of CIDs, such as axial spondyloarthritis, psoriatic arthritis, and psor...
#17567 : Role of the histone demethylase Kdm6b in ILC2 maturation and functional activation
Kdm6b is a histone demethylase that specifically demethylates tri-methylated histone3 lysine27 (H3K27me3), a repressive mark responsible for gene silencing. Its removal by Kdm6b enables the transcription of specific target genes. Kdm6b is expressed in many cell types such as neurons, hematopoietic stem cells, leukocytes or fibroblasts. Type 2 Innate Lymphoid cells (ILC2) are the innate counterpart of Th2 lymphocytes enriched at the barrier surfaces where they play a role in tissue repair and ant...
#17556 : Characterization of a broad spectrum chemical inhibitor targeting the endocytic pathway to prevent bacterial intoxications.
Bacterial toxins can induce a wide range of life threatening diseases and are at risk of bioweapon development due to their extreme toxicity and ease of production. Some AB-like toxins exploit the host cell endocytic machinery to enter into the cell cytosol where they exert their poisoning effects. Host-targeted therapy involving the development of small molecules interfering with key vesicular trafficking components hijacked by bacterial toxins offers to counteract toxin action. We have identif...
#17537 : The LeiSHield-MATI consortium: Investigating genomic adaptation of Leishmania parasites in endemic areas
Leishmania causes devastating human diseases – leishmaniases - representing an important public health problem in the Mediterranean basin and declared as emerging diseases in the EU due to climate change and population displacement. The LeiSHield-MATI consortium will for the first time investigate in an integrative fashion the complex parasite-vector-host interplay in cutaneous leishmaniasis affecting Morocco, Algeria, Tunisia, and Iran (MATI), using field isolates and human clinical samples. ...
#17437 : Mechanisms defining functional heterogeneity of anatomically distinct myogenic populations: insights from single nuclei-ATAC-seq data
Muscle stem cells in different anatomical locations are programmed with distinct upstream regulators prior to acquiring myogenic identity. This intriguing observation is most evident between cranial and trunk/limb muscles, and it correlates with the fact that cranial muscle stem cells are functionally more robust in terms of expansion capacity, resistance to stress, and engraftment efficiency, when compared to those in the limb. In this project we are using genomic approaches (sn-RNAseq and sc-...
#17370 : ISV detection in mosquito cell lines
To better understand the vector specificity of Aedes aegypti mosquito in the transmission of the alphaviruses CHIKV and ONNV, we are using an in vitro system to specifically depict critical viral infection steps at the molecular level: transcription and replication of the viral genome. This in vitro system requires mosquito cell transfections followed by luciferase quantification. For better describe the viral replication in mosquito cells, we need to characterize our mosquito cell lines since i...
#17345 : Modification and reliance of Chlamydia trachomatis on host cell metabolism
This project addresses two main questions: does Chlamydia trachomatis modify glycolysis and/or oxidative phosphorylation in the host, and do the bacteria need these metabolic pathways to complete their developmental cycle....
#17289 : Mosquito vector competence for Zika virus
Before the WHO considered it as a public health emergency of international concern in February 2016, Zika virus (ZIKV, Flavivirus, Flaviviridae) was a neglected mosquito-borne virus. First identified in Uganda in a sylvatic cycle, ZIKV has caused in few months millions cases, emerging in the five continents (Latin America, the Caribbean, Southeast Asia/Pacific Ocean, Africa/Indian Ocean, European countries (Portugal, Spain, France, Switzerland, the Netherlands)). We have initiated the most compr...
#17277 : Analysis of the viral diversity of coronaviruses in field samples.
Advances in high-throughput sequencing may allow more rapid characterisation of viral diversity in samples. However, although there are many tools to perform taxonimuqye assignment of the reads obtained, there is no automated pipeline to obtain the different sequences by species and genus, and when the depth is sufficient to apply correction algorithms. In the end, obtaining these sequences will allow us to better understand the diversity and prevalence of each of the species highlighted in our ...
#17266 : RNA virus discovery
Describing viruses of invertebrate vectors of disease, provides better understanding of evolution and host range for various virus groups. In addition to filling the gaps in the current knowledge of the virosphere, viromes can serve as necessary contextual data for ongoing disease control measures and outbreak preparedness. This project aims at delivering a comprehensive analysis of RNA viromes from RNA sequencing data....
#17210 : QTL mapping using new mouse reference genetic populations
New mouse genetic reference populations obtained from 8 distinct founder strains, including 3 wild-derived strains, have been developped since the 2000s and are now available. These populations captured around 95% of the existing murine genetic diversity and constitute a better model than standard inbred laboratory mouse strains. These populations constitute tools to identify new phenotypes and to map the causative genetic variants (QTL mapping) behind these phenotypes. These populations include...
#17102 : Development of a secure API for ARIAweb
Last year, we have developed the ARIAweb server for automated NMR structure calculation. The server was well received by the community (200+ users and ~1400 jobs performed) as of today. ARIAweb offers an interface for data conversion and interactive setup of ARIA calculations. Somme years ago, developers of NMR related software agreed on a new standard for storage of NMR data used in structure calculation, called NEF (NMR Exchange Format). The Structural Bioinformatics, as developer of ARIA comm...
#17084 : Development of a web server to calculate functional binding sites using Deep Learning
We have developed a computer tool, named InDeep, that relies on 3D fully convolutional neural networks to predict functional binding sites at the surface of proteins. These functional binding sites can take two forms, either a epitope binding site (location of a protein-protein interaction), or a druggable binding site (location for the binding of a future drug). Presently, the tool is already used on campus in several structural biology and drug discovery projects to support the identification...
#17079 : Comparing viral replication of intergenotypic hepatitis C virus Core recombinants
Using reverse genetics, we produced recombinant viruses within a prototypic HCV strain backbone, by substituting its core coding sequence by the equivalent sequences from from clinical isolates of different HCV genotypes. To verify that heterologous core sequences did not impair cross-talk with prototypic viral elements and could be used for comparative studies, we monitored the viral replication of our set of core intergenotypic viruses. For this, we quantified the amount of intracellular viral...
#17078 : Etude de l’évolution des Troubles Olfactifs chez les patients ayant une perte de l’odorat persistante des suites de la COVID-19
La pandémie de la COVID-19 est un défi médical inédit en particulier du fait de la nature systémique de cette pathologie. En effet, la COVID-19 affecte à la fois plusieurs organes et systèmes. L’atteinte cérébrale s’effectue de plusieurs façons : infection directe des cellules nerveuses par le SRAS-CoV-2, inflammation du système nerveux central avec, entre autre, invasion de lymphocytes T et activation de la microglie, inflammation systémique sévère qui inonde le cerveau d'agen...
#17077 : Microbiology Course : Practical course "Antibiotic resistance"
The general objective of the course (October 4th -15th) will be to obtain and characterize mutations leading to colistin resistance arising spontaneously during K. pneumoniae growth under laboratory conditions. During one week, the student will learn how to use complete genome sequence data to characterize mutations. Like last year, due to the SARS epidemic, bioinformatics analysis will be given to 2 groups of 10 students, each time for one week on the campus. If distance learning is required, ...
#17063 : Tests serologics anti-CNF1
Nous étudions la toxine CNF1 des E. coli uropathogènes. Cette toxine active des protéines ayant des activités pro-oncogéniques et pro-inflammatoires. Ces E. coli peuvent être en portage asymptomatique dans la flore intestinale de patients sains. Par des mesures quantitative du taux d’anticorps anti-CNF1 sérique nous cherchons à définir l’exposition de ces patients à cette toxine. Ici nous cherchons à définir si les différences mesurées entre groupes de patients sont significati...
#17060 : Understanding IL-23 role in chronic inflammatory diseases in innate and adaptative immune cells
The chronic inflammatory diseases (CID), as psoriasis, psoriatic arthritis (PsA) and axial spondyloarthritis (SpA), are clinically heterogeneous conditions that share common inflammatory pathways and derive from aberrant immune responses. GWAS strongly suggests that the IL-23/IL-17 pathway plays a key role in several CID. The successful treatment of psoriasis, PsA and axial SpA with IL-17A inhibitors has been validated. Interestingly, in literature, a strong GWAS association of IL23R with SpA wa...
#17058 : Development of a contributor management webpage for iPPI-DB.
We have recently developed and published our last version of iPPI-DB (https://ippidb.pasteur.fr/), our database of protein-protein interactions modulators. Thanks to the group of Hervé Ménager, the database is now hosted at Institut Pasteur and is completely remodeled, with a new web interface. As for many other databases, its success and interest for the community rely on the constant input of new data. For this, we also designed a contributor mode that allows anyone to add published data fro...
#17011 : A pipeline to detect correlated evolution on phylogenetic trees
Correlated evolution is the process by which the evolution of a trait (e.g., a genetic mutation) influences the evolution of other traits. Notably, when genetic mutations evolve together, the fitness effect resulting from the combination can be more or less important than the sum of the independent fitness effects. The disposition of mutations on a phylogenetic tree reflects to some extent the relationships that may exist between different mutations. One example is the evolution of co-occurrent ...
#17009 : Codon usage dependent translation and antibiotic stress in V. cholerae.
The aim of this study is to shed light into novel mechanisms which increase antimicrobial resistance (AMR) in Gram negative bacteria. In order to gain insight into new mechanisms involved in development of AMR, we study the strategies undertaken by Gram negative bacteria in response to low antibiotic stress, and particularly the role codon bias. Our preliminary results point to a role of codon usage in the survival to low antibiotics targeting various functions. Differences in codon decoding ma...
#17008 : Klebsiella MALDI-Typer
Klebsiella pathogens affect human and animal health and are widely distributed in the environment. Among these, the Klebsiella pneumoniae species complex, which includes seven phylogroups, is an important cause of community and hospital infections. The Klebsiella oxytoca species complex also causes hospital infections and antibiotic-associated haemorrhagic colitis. The unsuitability of currently used clinical microbiology methods to distinguish species within each of these species’ complexes l...
#17005 : Human ORFeome LIMS and website
Déploiement sur l'infra-structure de l'Institut Pasteur du LIMS permettant la gestion de la collection “ORFeome humain” à partir d'une base de code open-source contenant deux projets (une API et une interface web). Cet outil informatique permet la gestion de la collection ainsi que des sous-collections qui en découlent, il permet également d'effectuer des recherches multi-critères et d'éditer des listes de cherry-picking dans un format directement utilisable sur la plateforme robotique...
#16987 : Rabomism - Understanding rabies virus tropism
Factors determining RABV tropism are largely unknown. Here, we are identifying the susceptibilities and influence of glial cells on RABV infection....
#16982 : Statistical comparisons of Oroboros measurements
We seek to make the appropriate statistical comparisons of oxygen consumption and mitochondrial membrane potential measurements in paired, high-resolution respirometry measurements between control and experimental samples...
#16959 : Imprinting by immune cross regulation modulate airway allergic inflammation
There are papain treated and papain+CPG treated group. From mouse lung tissue, I'd like to find out the target cell and their key molecule through scRNAseq and receptor-ligand analysis. When I get the target cell, I want to do ATACseq (or scATACseq) of target cell to see if memory of previous exposure to inflammatory stimuli represented by chromatin accessibility and which has something to do with 2nd exposure of same allergen....
#16953 : ANR Arbovec- CHIKV/Aedes interactions
To better understand the vector specificity of Aedes aegypti mosquito in the transmission of CHIK virus, we try to identify genes involved in the primary responses of the viral infection when the virus is still in the midgut of mosquitoes, prior to the crossing of the gut epithelium. This investigation will be performed via mRNAseq from sequences of pools of 8 mosquitoes that fed on blood (controls) or on blood +CHIKV (infected mosquitoes)....
#16898 : PacBio sequencing of DM1 cells treated with a TALEN
Myotonic dystrophy type 1 (DM1 or Steinert disease) is a monogenic neurodegenerative disorder due to the expansion of a CTG trinucleotide repeat in the 3' UTR of the DMPK gene on chromosome 19. We developed a strategy to induce a DNA double-strand break (DSB) within the expanded repeat in order to contract it below the pathological range in humans. This approach was successful in yeast and mouse cells and we are now trying to apply it to human cells from a patient affected by DM1. This patient w...
#16896 : Single-cell and spatial transcriptomics of cells of the hematopoietic and stromal lineages in the zebrafish embryo
Hematopietic stem cells (HSCs) are essential for supplying blood and immune cells of the vertebrate body. They are essentially formed during the embryonic time-period, from the wall of vessels and in particular the dorsal aorta. Their survival and self-renewal capabilities are depending on environmental conditions provided by hematopoietic niches among which the bone marrow microenvironment, in adult mammals. During embryonic development, HSC precursors home in transient niches; the main organ b...
#16876 : Identification of ASD markers using HD-EEG
Autism Spectrum Disorder (ASD), a disorder of social communication and restricted and stereotyped interests, represents a major societal challenge with its prevalence of 2.93% (Baio et al., 2018). Since genetic factors have been identified, their links with phenotypic expression (incl. neuroanatomical aspects) are being explored (Bourgeron et al., 2015). The first neuroanatomical studies are promising, and reinforced by the development of interaction neurosciences, notably with the high-density ...
#16870 : Transcriptomics on mosquitoes
This projects aims at performing transcriptomics on mosquitoes infected with arboviruses such as Dengue or Zika virus....
#16850 : Stem cells and systemic inflammation
Our project aims to study the consequences of the systemic inflammation on muscle stem cells (MuSCs). To address this question, we use two in vivo mouse models associated with high systemic inflammation, an acute viral respiratory infection, with the influenza virus, and a solid tumor growth. Both paradigms are associated with muscle catabolism, named cachexia, which is intensively studied in the cancer field. However, most studies are focusing on the muscle fibres, the contractile apparatus of ...
#16847 : Natural variation of TE content and expression in Aedes aegypti mosquitoes
Investigating the genetic basis of an organism’s phenotype typically focuses on genomic sequences annotated as genes. This traditional approach ignores repeated sequences such as transposable elements (TEs) that often make up a large fraction of the genome and contribute significantly to genetic diversity, including variation in genome size. TEs are mainly known to play an important role in genome architecture and evolution through their mutational potential but TE expression itself can also r...
#16822 : Genome analysis of the immunostimulatory commensal SFB
The gut microbiota is instrumental in stimulating, shaping and educating the host immune system, both in and outside of the gut. One of the most immunostimulatory commensals identified to date is the unusual bacterium Segmented Filamentous Bacteria (SFB). SFB intimately attaches to absorptive epithelial cells in the ileum after weaning in a host-specific manner. We aim to do compare the genomes of SFB from a range of vertebrate species to identify shared and strain-specific differences that may ...
#16817 : BIGSdb-Pasteur web pages and design renewal
The project aims to develop a website providing information related to BIGSdb-Pasteur, https://bigsdb.pasteur.fr/, and harmonize its web design with Pasteur website...
#16813 : 3DPATH
Complex chronic diseases such as type 1 and 2 diabetes are caused by the accumulation of genetic, microbial and lifestyle factors. The number and complexity of such factors makes prediction of pathogenesis and therapy particularly difficult. Although a single factor is rarely sufficient to trigger pathology, genetic and environmental factors have so far been studied in isolation. Nevertheless, a substantial number of genetic variants have been associated with disease risk and the concomitant lif...
#16799 : JASS 2 : Integrating functional annotation to a multi-trait GWAS web application
JASS is a python package that handles the computation of the joint statistics over sets of selected GWAS results, and the interactive exploration of the results through a web interface (https://jass.pasteur.fr/index.html). The functionalities of the current web interface include: the interactive visualization of multi-trait GWAS results, the sharing of results through a permanent link and generation of static summary plots. This work and its accompanying tools has been described in a publicatio...
#16791 : Analysis of genes transcription profiles in E.coli after expression of the T4 phage protein Ndd
Ndd expression in E.coli induces nuclear disruption where the nucleoid is swiftly relocated from a central position in the cell to a submembrane location. RNAseq analysis showed Ndd expression induces the differential expression of hundreds of E.coli genes. We would like to see if some of those genes are related to regulation networks of several nucleoid associated proteins....
#16789 : Page web modélisation covid-19 pasteur
Le projet a pour objectif de développer une page web pour présenter les travaux de modélisation de la pandémie de la COVID-19 au grand public....
#16769 : Asymmetric heart morphogenesis
Establishment of a left-right asymmetry is essential for the function of the heart, which is to ensure a double blood circulation. This asymmetry is initiated during an embryonic process, in which the heart tube acquires a loop shape. The molecular cascade at the origin of left-right asymmetry is well established and involved in the severe heart defects of the heterotaxy syndrome. However, another 20% of heart malformations display cardiac chamber misalignment and their origin is poorly understo...
#16763 : Validation of interactions between SARS-CoV-2 proteins and cellular proteins
We are working on the validation of protein interactions between SARS-CoV-2 proteins and human proteins that have been identified by Bio-ID. Our project is the validation of those interactions using our NanoLuciferase two-hybrid system....
#16730 : Characterization of Salmonella mutants
Identification of a secondary mutation which likely appeared during the construction of a mutant strain of Salmonella serotype Typhimurium...
#16720 : Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms
The worldwide SARS-CoV-2 outbreak poses a serious challenge to human societies and economies. SARS-CoV-2 proteins orchestrate complex pathogenic mechanisms that underlie COVID-19 disease. Thus, understanding how viral polypeptides rewire host protein networks enables better-founded therapeutic research. In complement to existing proteomic studies, in this study we define the first proximal interaction network of SARS-CoV-2 proteins, at the whole proteome level in human cells. Applying a proximit...
#16696 : Regulation of nasopharyngeal microbiome in normal healthy individuals
Immune responses are conditioned by host genetics as well as environmental stimuli that include disease-causing pathogens but also a diverse community of commensal micro-organisms (bacteria, fungi, viruses). However, we still have little information on how immune reactivity is regulated in normal healthy humans. Knowledge in this arena is critical since it could lead to experimental approaches that might impact on the amplitude and duration of immune responses against pathogenic infections. A be...
#16693 : Mosquito vector competence for different RVFV variants
Historically circulating in Africa, Rift Valley fever virus (RVFV) was firstly identified in Kenya in 1930, and responsible for dozens of outbreaks in Africa in the past decades. As an arbovirus, RVFV is mainly transmitted by mosquito vector, and needs to be altered between mammalian host and mosquito vector for maintaining the genome stability. In this project, we are analysing the mosquito vector competence for several RVFV variants obtained from different host cells, to better interpret the r...
#16686 : Transcriptional profiling of the innate immune response of human fibroblasts of the LabEx Milieu interieur collection: interindividual variability and response to infection
The LabEx Milieu interieur (MI) project is a clinical study aiming to define the natural variability of the human immune response. Fibroblasts were prepared from skin biopsies of 300 of the 1000 healthy donors (30 men and 30 women in each of 5 decades from 20 to 69 years) by Genethon. Each primary line is annotated by metadata derived from the systematic genotypic-phenotypic analysis Labex-MI (serology, genomic analyzes, proteomics, transcriptome, microbiota, clinical data and epidemiological se...
#16678 : Etude des TSS alternatif chez Cryptococcus
Dans les années récentes, l’utilisation de données RNA-Seq nous a permis de ré-annoter le génome des trois souches de références de, respectivement, C. neoformans, C. deneoformans et C. deuterogattii (JANBON et al. 2014; GONZALEZ-HILARION et al. 2016; FERRAREZE et al. 2020). En utilisant des données de TSS-Seq et 3UTR-Seq, nous avons identifié les extrémités de chaque gène codant, ce qui nous a permis de décrire en détail la structure des Transcript Leader (TL) (WALLACE et al. 20...
#16644 : HPV RNA-SEQ
HPV RNA-Seq, a novel and unique molecular test that allows detection of pre-cancerous lesions of the cervix from cervical samples....
#16637 : basic alignment/visualisation pipeline
Establishment of simple and basic procedures for alignment/visualisation of NGS data for unexperienced biologists...
- Claudia CHICA
- Rachel LEGENDRE
- Fabien MAREUIL + 1 operator
#16636 : Defining the effects of TNF-blockers and IL-17A-inhibitors on immune responses in spondyloarthritis patients, analysis of protein and gene expression signatures
Anti-TNF therapy has proven effective to reduce inflammation and clinical symptoms in SpA, however, the high rate of non-responsiveness (30-40%) to TNFi exposes a substantial fraction of patients to side effects without clinical benefit, and it is still not possible to determine which patients will respond to TNF inhibitors (TNFi) before treatment initiation. The recent introduction of antibodies blocking IL-17A has expanded the therapeutic options for axial SpA (axSpA), as well as psoriasis and...
#16635 : Regulation of IL-23 Receptor expression
Chronic inflammatory diseases (CID) are clinically heterogeneous conditions that share common inflammatory pathways and derive from aberrant immune responses. Genome-wide association studies (GWAS), together with mouse models of autoimmune disease, demonstrated the implication of the IL-23 cytokine pathway in several CID. The overall goal of our work is to improve our understanding of the role of IL-23 in the pathophysiology of CIDs, such as axial spondyloarthritis, psoriatic arthritis, and pso...
#16631 : The master regulator of virulence gene expression in Group B Streptococcus
This RNA-seq project aims to characterize the function of genes regulated by the master regulator of virulence in Group B Streptococcus....
#16608 : Changes in cellular pathways during SARS-CoV-2 infection upon drug treatment
SARS-CoV-2 depends on the activation or inactivation of specific cellular pathways for efficient replication. The project screened small molecule compounds that affected epigenetic regulation of such pathway. The project aims to characterize these specific pathways, so identify specific steps important in the viral replication cycle and with this to describe the mode of action of these compounds....
#16604 : Single-cell characterization of autoreactive IgG-secreting cells in Immune thrombocytopenia
Immune thrombocytopenia (ITP) is an autoimmune condition characterized by an autoantibody response against platelets, driven by pathogenic plasma cells often found in the spleen. This autoreactive plasma cell population remains poorly characterized, especially in terms of antibody affinity and anatomical distribution. In order to tackle this problem, we have developed a microfluidic platform to characterize platelet-specific plasma cells isolated from ITP patients, in terms of their IgG secretio...
#16594 : Identifying new population(s) of NK cells involved in memory to bacterial infection
In recent years the concept that only adaptive immunity mediates memory responses has been challenged by several examples of innate immune memory, as shown for macrophages and NK cells. NK cells are innate lymphoid cells, with well-established roles in targeting cancer and virally infected cells, and in addition, are crucial players in antibacterial immunity. Similarly to what has been shown in response to virus, our work is revealing that NK cells maintain a memory of bacterial infection, as se...
#16585 : Phages - bacteria interactions network of the healthy human gut
With an estimated 1031 particles on earth, bacteriophages are the most abundant genomic entities across all habitats and important drivers of microbial communities. Growing evidence suggest that they play roles in intestinal human microbiota homeostasis, and recent metagenomics studies on the viral fraction of this ecosystem have provided crucial information about their diversity and specificity. However, the bacterial hosts of this viral fraction, a necessary information to characterize further...
#16560 : Induction of highly efficient HIV-specific CD8+ T cell responses
The key role of CD8+ T-cells in controlling HIV replication has been particularly well established. Functional and metabolic properties of HIV specific CD8+ T cells appear to be essential for an effective control of the virus, as shown in HIV-1 and HIV-2 controllers. Mounting of functional CD8+ T cell responses is dependent on the effective priming of optimal antigen specific memory like CD8+ T-cells. However, factors that may dampen or promote effective priming of CD8+ T-cell responses during H...
#16536 : Transcriptional analysis of injured skeletal muscle
This project aims at characterizing the transcriptional signature of skeletal muscle during regeneration....
#16522 : A cost-effective molecular Tool for Strengthening Antimalarial drug Resistance surveillance in Africa (TSARA)
In the TSARA project, we aim at developing and validating a molecular platform (Dual Index Targeted Amplicon Deep Sequencing on Illumina iSeq) and a dedicated bioinformatics pipeline for targeted high throughput sequencing of genetic loci related to antimalarial drug resistance. The iSeq Illumina platform, proposed here, is designed for dual indexing of samples, consisting of a 3’ and 5’ individual barcode, which allows the user to connect every sequence generated to a specific sample (up to...
#16423 : Track Analyzer
Track Analyzer is Python-based data visualization pipeline for tracking data. It does not perform any tracking, but takes as input any kind of tracked data. It analyzes trajectories by computing standard parameters such as velocity, acceleration, diffusion coefficient, divergence and curl maps, etc. This pipeline also offers a trajectory visualization in 2D (and soon in 3D rendering), using a selection tool allowing to perform some fate mapping and back-tracking....
#15884 : Setup of bioinformatic pipelines for paleo(meta)genomics
Paleo(meta)genomics is an emerging and rapidly growing field where most is yet to be done. In most cases, it consists in the analysis of ancient DNA high-throughput sequencing data obtained from archaeological material or historical samples, and the goal is to retrieve and interpret the genomic information from species that from the past (microbial, eukaryotic, etc.) It combines tools borrowed from different fields, such as genomics, computational biology, microbial ecology, phylogenetics, pop...
#15876 : Analyse statistique de données de phénotypage à haut débit
Ce projet, discuté avec le groupe « Statistiques », a pour but de proposer une analyse statistique des données quantitatives de phénotypage à haut débit générées au laboratoire. Le groupe Statistiques se propose de former et d’accompagner C. Maufrais à ce type d’analyse. Notre jeu de données de phénotypage consiste en des données multivariées (mesure de 16 variables sur 42 souches cultivées dans 100 conditions de croissance, avec réplicats biologiques et techniques)....
#15813 : Identification, structural and functional analyses of peptides from SARS-Cov2 binding with high affinity to MHC-E and impact on NK cell responses in SARS-Cov2 infection
We propose to identify peptides derived from the S protein that can modulate the HLA-E restricted activity of NK cells. Through in-silico analyses, we have already identified in the S protein of SARS-Cov1, SARS-Cov2 and MERS-Cov regions coding for peptides with HLA-E binding motifs. We will perform functional and structural analyses of the binding of these peptides to MHC-E. We will study MHC-E restricted responses of NK cells in blood and tissues during SARS-Cov2 infection in non human primates...
#15731 : Genome organization and synteny analysis of Yersinia pseudotuberculosis strains responsible for the Far-East Scarlatine-Like Fever
The Yersinia pseudotuberculosis complex comprises the plague pathogen Yersinia pestis, the enteropathogen Yersinia pseudotuberculosis, as well as specific sub-group of Y. pseudotuberculosis strains responsible for the Far-East Scarlatine-Like Fever (FESLF). We have sequenced the genomes of FESLF strains and we are interested in investigating the genome organization of these bacteria....
#15721 : Yersinomics SynTView instance deployment for 85 genomes and development of a SynTView javascript local view
Yersinia pestis, Y. pseudotuberculosis and Y. enterocolitica are major human pathogens. Bacnet is a Java based platform to develop websites for multi-omics analysis. Yersinomics allows comparative genomics and transcriptomics between pathogenic Yersinia species. In the tool a SynTView module is dedicated to study synteny profiles between several strains. We use complete genomic data from Yersinia bacterial strains obtained in the refseq ftp site to compute the orthologs between three pathogen...
#15696 : Identification of the genetic basis of bacteriophage-resistant isolates
Bacteria exposed to bacteriophages deploy several defence systems that we wished to identify by genomes sequencing of bacteriophage-resistant isolates...
#15658 : Conditionnal formating in an excel file for certain data over a certain period of time.
We aim to identify, on an excel file that compiles molecular and epidemiological data, when certain results happen with a certain frequency in a determined period of time....
#15485 : Providing correlationPlus software to the scientific community for analysis of dynamical correlations in biological macromolecules
Molecular dynamics simulations and elastic network models are two widely used computational methods for investigation of dynamics of biological macromolecules. These methods can reveal dynamical correlations between residues, nucleotides, domains and chains of biological macromolecules. Even though analyses of these correlations are employed frequently, there is not an application and API that can facilitate the analysis and the visualization of them. A coherent API/app can accelerate the analys...
#15457 : Search for genetic determinants of aminoglycoside tolerance
Antibiotic resistance development is a public health liability and treatens treatment of bacterial infections. We are inetersed in genetic determinant of antibiotic resistance in Gram negative bacteria. We have identified V. cholerae mutants which are more tolerant to aminoglycosdies. Our aim is to identify cellular processes involved and characterize molecular mechanisms....
#15447 : Modulation of Flu transmission in Niger , according to climate variations over the past ten years
Modulation of infectious diseases transmission by climate conditions must be investigate in Sahel to prevent epidemics. Registration of data on flu transmission and on rainfalls+ temperature was conducted over the last ten years by the Flu national reference center in Niamey. Time series analysis must be conducted to investigate the correlation between the number of cases and climatic conditions....
#15424 : Effect of metabolic disturbance on the host transcriptional profile during Chlamydia infection
Chlamydia trachomatis is an intracellular bacterium. We have observed that some of the epigenetic changes in the host that occur in infection can be reversed by modifying the culture conditions. We will measure the impact this has on the global transcriptional response of the host to infection....
#15377 : Correlative analysis between lipid droplets number and volume in hepatocytes infected by hepatitis C virus variants
Hepatitis C virus (HCV) infection is a slow and asymptomatic progressive liver disease leading to metabolic disorders such as steatosis, an accumulation of lipid droplets (LDs) in hepatocytes. We have assessed the interplay between HCV variants recovered from chronically infected patients and LD content in infected hepatoma cells, through quantitative imaging approaches....
#15355 : Biology of noncoding regulatory elements in Anopheles
Enhancers are cis-regulatory elements that control developmental and spatial gene expression in eukaryotes. Enhancers have been little studied in mosquitoes, including the Anopheles vectors of malaria....
#15354 : Genetic association of malaria susceptibility by Anopheles population resequencing
The highest global malaria prevalence is in Africa, where the most important vectors are members of the Anopheles gambiae species complex. We generated a large curated panel of infected wild Anopheles gambiae mosquitoes in West Africa to analyze for association of genetic variants with susceptibility to the human malaria parasite Plasmodium falciparum....
#15353 : NGS-based genetic linkage mapping in Anopheles
The mechanisms underlying Anopheles mosquito susceptibility to malaria parasite infection in nature are not understood. We infected wild Anopheles pedigrees in West Africa to map loci for susceptibility to the human malaria parasite Plasmodium falciparum. Individuals from phenotyped pedigrees were entirely sequenced in order to identify and fine-map segregating loci....
#15228 : Coaching in R
Background : The Immunoregulation Unit is composed at present of: Lab Head, one senior staff scientists, two “ingegnieurs” (one IP, one Fondation APHP), two PhD students. The focus of the research is the study of immuno-mechanisms in the pathogenesis of chronic inflammatory diseases, and of the molecular basis of response to treatment. All members of the lab have expressed an interest in acquiring basic R skills for the analysis of large gene expression data sets, collected from the study o...
#15173 : Analysis of the transcriptome during lyssavirus infection in torpid bat: an in vitro model. Act 1
The aim of this study is based on the analysis of the transcriptome during the infection with European bat lyssavirus type 1 (EBLV-1) in torpid bat. This study will be conducted using an in vitro model using another bat cell line from an European bat....
#15170 : Statistical analysis of qRT-PCR data
We studied the impact of deletion of different component of a regulatory system on the transcription of specific genes....
#15169 : French GWAS Covid webpage
Institut Pasteur and institut Imagine will coordinate a french collection for genome-wide association study of COVID suceptibility and severity. This collection will contribute to the ongoing major international efforts addressing this question (https://www.covid19hg.com), but it will also be a major platform for a range of other national and international collaborations addressing host biology questions, and for integrative approaches including host genomics data (metabolomic, transcriptomic…...
#15163 : Left-right patterning of heart precursors
Left-right asymmetry of the heart is essential for establishing the double blood circulation. Impairment of left-right embryo patterning is associated with severe congenital heart defects. During embryonic development, the heart initially forms as a straight tube. While it elongates, it acquires the shape of a rightward helix, a process referred to as heart looping. Previous work suggests that dynamic signaling in the heart precursor cells are essential for heart looping completion, but so far o...
- Anne BITON
- Rachel LEGENDRE
- Emeline PERTHAME + 1 operator
#15135 : An integrated software having a graphical user interface for the analysis of time-lapse images of bacterial microcolonies
In our laboratory we focus on the single-cell biology of tuberculosis. Phenotypic variation helps bacterial cells to endure stressful environmental conditions, and is one of the possible causes of antibiotic persistence and chronic infections. We have recently demonstrated that phenotypic variation is indeed associated with a different response to a class of antimicrobials, in particular in subpopulations of mycobacteria experiencing different levels of DNA damage. Therefore, targeting phenotypi...
#15116 : Study of the deficiency in lactose utilization by Shigella strains
Bacteria of Shigella species are responsible for bacillary dysentery (shigellosis) in humans. A characteristic feature of these bacteria, used for identification purposes, is their inability to use lactose as a carbon source, in contrast to the closely related species Escherichia coli. We recently isolated clones of Shigella exhibiting a Lac+ phenotype on Drigalski medium and we are attempting to identify the gene(s) involved in this phenotype....
#15114 : Proteomic analysis of Listeria monocytogenes molecules impacted upon exposure to Listeriolysin S
Listeriolysin S (LLS) is a bacteriocin from Listeria monocytogenes that targets other Gram-positive bacteria, including Listeria monocytogenes itself. In order to understand the mechanism of action of LLS on target bacteria, we exposed the LLS-susceptible L. monocytogenes strain 10430S to the bacteriocin. We identified the proteome of the target bacteria with the goal of understanding which metabolic pathways are upregulated upon exposure to LLS....
#15113 : A cost-effective molecular Tool for Strengthening Antimalarial drug Resistance surveillance in Africa (TSARA)
In the TSARA project, we aim at developing and validating a molecular platform (Dual Index Targeted Amplicon Deep Sequencing on Illumina iSeq) and a dedicated bioinformatics pipeline for targeted high throughput sequencing of genetic loci related to antimalarial drug resistance. The iSeq Illumina platform, proposed here, is designed for dual indexing of samples, consisting of a 3’ and 5’ individual barcode, which allow the user to connect every sequence generated to a specific sample (up to ...
#15084 : Research of orphan LytTR DNA-binding domain
We want to look at the prevalence of protein composed of an orphan LytTR DNA-binding domain in diverse bacteria....
#15067 : Building a database with a pattern mining system designed for virus nucleic acid data
Because of the increasing biological data generated due to next-generation sequencing of the genetic material of organisms, storing and analyzing these data have become challenging both for molecular biologists and computer scientists. Here, we propose to design a system that attempts to solve this from building a secure repository up to designing algorithms that process sequences to produce biological insights, particularly mining for sequential patterns present in the sequences. Discovering se...
#15066 : Small RNA signature on RIG-I like receptors
The RIG-I like receptors (RLRs) play a major role in sensing viral infection to initiate and modulate antiviral immunity. These are three RNA helicases entitled RIGI, MDA5 and LGP2 that interact with particular signatures of viral RNA molecules in cytoplasm of infected cell triggering a downstream signalling cascade resulting in the expression of type-I IFNs, proinflammatory cytokines and divers set of antiviral genes. We have recently generated stable cell lines expressing tagged RLRs. By apply...
#15049 : Determination of RABV RNAs signatures recognized by RLRs
Rabies virus (RABV) is a causative agent of lethal neurological disease. It presents a public health threat in the world resulting in more than 59,000 human deaths every year around the world. RABV possesses negative strand RNA genome, 11.9 kb, encoding five viral proteins: Nucleoprotein (N), Phosphoprotein (P), Matrix protein (M), Glycoprotein (G) and polymerase or Large protein (L). Structural modelling of L protein suggested that L contained different conserved domains: i) RdRp for RNA transc...
#15033 : Identification of internal methylations of RABV mRNAs using RiboMeth sequencing approach
Rabies virus (RABV) is a causative agent of lethal neurological disease, a member of Lyssavirus genus, belonging to Rhabdoviridae family in the order Mononegavirales. It presents a public health threat in the world resulting in more than 59,000 human deaths every year around the world. RABV possesses negative strand RNA genome, 11.9 kb, encoding five viral proteins: Nucleoprotein (N), Phosphoprotein (P), Matrix protein (M), Glycoprotein (G) and polymerase or Large protein (L). Structural modelli...
#15011 : Collaboration between CETEA, C2RA and Hub for optimization of experimental designs (3R)
As part of a collaboration between the CETEA, the C2RA and the Hub of Bioinformatics and Biostatistics, we aim at refining the experimental projects by improving their design through reviewing projects, training project designers and developing softwares....
- Anne BITON
- Pascal CAMPAGNE
- Vincent GUILLEMOT + 3 operators
#15004 : Parvimonas micra's impact on primary human colonic cells DNA methylation
Parvimonas micra is a gram+ anaerobic coccus bacteria associated with colorectal cancer (CRC). The stool of patients with CRC has higher Parvimonas micra concentration compared to healthy individuals. It is also present in the colonic mucosa of CRC patients. Even if we find it in the adjacent healthy tissue, it is predominantly found in the tumor. Furthermore, it is correlated with the CpG island methylator phenotype (CIMP), a particular subtype of CRC. More specifically, it is associated with ...
#15003 : Analysis polymorphism in a specific gene of Aedes aegypti using exome sequencing data.
We are currently characterising a set of genes that are involved in the yellow fever mosquito, Aedes aegypti, vector competence. We would like to investigate the polymorphisms of those genes using exome sequencing data....
#14989 : Mitochondrial polarization identifies functionally mature human NK cells
Energy demands vary widely depending on cellular activation states. Here we perform an integrated bioenergetic analysis (epigenetic, transcriptomic and metabolomic) of the human CD56Br and CD56Dim natural killer (NK) cell subsets under steady-state conditions and after cytokine activation. We found that CD56Dim NK cells were metabolically active at steady state, but that both subsets increased bioenergetic properties upon priming with IL-15, with metabolic profiles similar to tonsillar NK cells....
#14985 : Genome-Wide Mapping of Integron Cassette Integration Target Sites.
We wish to study the genome-wide integration preferences of integron cassettes in the MG1655 Escherichia coli genome....
#14968 : Analysis of microbiota in Anopheles mosquitoes
Cepia mass produces two species of Anopheles mosquitoes for research teams studying malaria. The aim of this project is to assess 1) whether or not the compostion of the bacterial microbiota fluctuates over time and if so to what extent ; 2) if there are significant variations can these be correlated with the degree of infectability by plasmodium parasites and/or the fitness of the mosquitoes (measured by their survival rate)....
#14967 : Transcriptional regulation of bacterial physiology during host-pathogen interaction
The aim of this RNA-seq project is to characterize three transcriptional regulators of Streptococcus agalactiae, the main etiological agent of bacterial meningitis in neonate, and one transcriptional factor of Enterococcus faecalis, a second Gram-positive opportunistic pathogen....
#14680 : Modulation of cellular pathways involved in neuropathology of rabies infection
Viruses have evolved powerful countermeasures to evade host innate immunity, which produces immediate, but non-specific, immune response during infection. Among viruses possessing RNA genomes, the order of negative-single-strand viruses (Mononegavirales) encompasses many human and animal pathogens that cause severe disease, including measles virus, mumps virus and rabies virus. Rabies virus is known for its neurotropic retrograde progression from the site of transmission to brain parenchyma, and...
#14672 : Flemmingsome: A Midbody Remnant Proteome Database
The central part of the intercellular bridge connecting the two daughter cells during cytokinesis is a highly dense structure named the Midbody first described by Flemming in 1891. We set up an experimental protocol to purify intact, detergent-free MBRs in order to have the full proteome of this organelle. Quantitative, label-free proteomics enabled us to identify MBR proteins, that we named the “Flemmingsome”, and 489 of them were found enriched as compared to whole cell lysates, thus name...
#14671 : Functinal analysis of proteome and phopshoproteome changes in murin intestine – mechanism of Streptococcus gallolyticus-induced carcinogenesis
Streptococcus gallolyticus sous espèce gallolyticus, autrefois dénommée Streptococcus bovis biotype I, est une bactérie de la flore intestinale qui constitue une cause émergente de septicémies et d’endocardites chez les personnes âgées. Depuis plus de 50 ans, les études épidémiologiques indiquent l’existence d’une forte association entre les infections invasives à S. gallolyticus et le CCR (cancer colorectal) (Pasquereau-Kotula et al., 2018). Néanmoins, le rôle exact de S.gal...
#14667 : improvement of new methodology for oral infection on mice
Oral administration is a preferred model for studying infection by bacterial enteropathogens such as Yersinia. In the mouse model, the most frequent method for oral infection consists of oral gavage with a feeding needle directly introduced in the animal stomach via the esophagus. In this study, we compared needle gavage to bread feeding as an alternative mode of bacterial administration....
#14643 : Plasmodium vivax Invasion Pathways into Human Reticulocytes - VIPers
In this project, we aim to identify P. vivax ligands involved in host cell invasion and understand how P. vivax has gained the capacity to infect reticulocytes from Duffy-negative individuals. Our strategy will be based on a 2-step approach by taking full advantage of next-generation sequencing and functional biological analysis (including in vitro invasion assays and infection in humanized mice) and by availing our access to P. vivax isolates from both Duffy-negative and Duffy-positive vivax ma...
#14612 : Implementation of the ViroScreen workflow in Galaxy
The ViroScreen workflow is a bioinformatic pipeline dedicated the the analysis of NGS metagenomic data, especially in the field of virology (virome analysis). The aim of the project is to implement this bioinformatic workflow, developed with Corinne Maufrais (Bioinformatics and Biostatistics Hub), in Galaxy, to make it easly accessible to the scientific community, in easy-to-use way....
#14611 : Deciphering the transcriptome profil during rabies infection in brain in mouse and in human
The transcriptome signature during rabies infection will be analyzed both in animal model (mouse) and in human, at the central nervous system level, to identify the main canonical pathways involved during the infection....
#14608 : Integration and advanced statistical analyses of complex datasets for host factor identification involved in Salmonella and Shigella intracellular niche formation
Salmonella enterica serovar Typhimurium (S. Tm) and Shigella flexineri actively invade non-phagocytic human epithelial cells in a similar fashion. Both pathogens use bacterial effectors injected through a Type III Secretion System to interfere with host pathways for invasion, survival and proliferation within host cells. Our team has performed different screening approaches to identify subverted host pathways during infection. The wide range of obtained data includes functional data from loss-of...
#14607 : Récupération des données associées aux séquences de génomes de Klebsiella pneumoniae téléchargées du NCBI
Dans le cadre d'une étude de souches de Klebsiella pneumoniae multirésistantes, nous avons besoin de comparer nos génomes avec ceux présents dans la base de données ncbi. Dans ce cadre, nous avons téléchargé l’ensemble des gènome de K. Pneumonie disponible fin novembre 2019. Nous utilisons des outils comme kleborate pour obtenir le Sequence Type, le résistome et des informations sur des mutations dans les gènes de la capsule et les porines. Afin de lier les caractéristiques génét...
#14589 : Development and design of new functionalities for MEMHDX, a web application dedicated to the statistical analysis and vizualization of large HDX-MS datasets.
Hydrogen Deuterium eXchange followed by Mass Spectrometry (HDX-MS) is a recognized biophysical tool in structural biology capable of probing protein/ligand interactions, conformational changes, and protein folding and dynamics. Over the last decade, major improvements in the technology have been made (i.e., refrigerated UHPLC system, mass spectrometers with enhance resolution and sensitivity…) allowing the structural analysis of highly challenging biological systems. The characterization of su...
#14587 : Off-target sites of Cas endonucleases targeted to trinucleotide repeats
Many neurodegenerative disorders are caused by the large expansion of a repeated sequence, called a "trinucleotide repeat". Our laboratory is using the CRISPR-Cas family of endonucleases in order to shorten the repeat tract below the length that is known to be pathological in humans. Some of the nucleases tested are very efficient at cutting the repeat tract, but in order to make this approach a viable gene therapy strategy, we must ensure that the nuclease is not inducing mutations in other par...
#14555 : Identification of non-coding RNAs under the control of the PerR regulators
Pathogen leptospires are responsible for the zoonotic disease leptospirosis. During infection, Leptospira are confronted with dramatic adverse environmental changes such as deadly reactive oxygen species (ROS). Defenses against ROS, e.g. peroxidase activity, are crucial for Leptospira virulence and the adaptive response to ROS is controlled by PerR regulators. We aim at studying how small non-coding RNA participate in the adaptive response to oxidative stress in pathogen Leptospira....
#14510 : Shigella targeting of human colonic Lamina Propria Mononuclear Cells
The enteropathogen, Shigella, is highly virulent and remarkably adjusted to the intestinal environment of its almost exclusive human host. Key for Shigella pathogenicity is the injection of virulence effectors into the host cell, via its type three secretion system (T3SS), initiating disease onset and progression. T3SS-mediated host cell targeting is associated with Shigella invasion and dissemination in epithelial cells. Yet, our group reported the direct targeting of human lymphocytes by an in...
#14386 : Cartography of the expansion of pathogenic Yersinia in Vietnam
We aim to establish a comparison of the genetic diversity of different Yersinia spp. genomes and their geographic coordinates in order to characterize the possible associations of genotypes and spatial distances from an epidemiological point of view...
#14385 : Evaluation of the mutation rate per site and dN/dS in the genomes of Yersinia enterocolitica
Evaluation of the mutation rate per site and dN/dS of the genomes of 4 Yersinia enterocolitica strains isolated from the same patient during 14 years....
#14337 : Long-term preservation of a Campylobacter fetus strain and genomic stability
Ensuring good storage conditions is fundamental for a long-term conservation of bacterial strains. Freeze-drying, freezing, and liquid nitrogen are methods the most frequently used for long term storage. The effectiveness of these different methods to ensure the stability of the genetic characteristics of the bacterial strains over the long term preservation needs to be evaluated. The submitted project aims to see what impact has the long term preservation at the genomic level and if the differe...
#14332 : Proteomic analysis of the intracellular compartments containing Brucella abortus
Brucella abortus is a zoonotic pathogen that affects cattle by inducing abortion. Humans are accidental hosts that acquire the infection through contact with animal fluids from infected animals. The pathogenesis of brucellosis relies in the ability of B. abortus to survive intracellularly. This bacterium enters host cells, evades the lysosomal route and re directs its traffic to the endoplasmic reticulum. The type IV secretion system VirB has been shown to be crucial for the intracellular fate o...
#14331 : Spatial analysis of cysticercosis seroprevalence in villages of Ivory Coast
soumis plus tard...
#14328 : SHERLOCK4HAT - WP1.1
African trypanosomes are transmitted by the bite of the tsetse fly and cause the debilitating, and often fatal, neglected tropical disease sleeping sickness, or Human African Trypanosomiasis (HAT). Trypanosoma brucei gambiense, the parasites responsible for 98% of human cases, first reside in the patient blood and skin for months to years before invading the central nervous system, where they cause the neurological symptoms of the disease. HAT is approaching elimination, with the number of cases...
#14231 : Implementation of the ViroScreen workflow in Galaxy
The ViroScreen workflow is a bioinformatic pipeline dedicated the the analysis of NGS metagenomic data, especially in the field of virology (virome analysis). The aim of the project is to implement this bioinformatic workflow, developed with Corinne Maufrais (Bioinformatics and Biostatistics Hub), in Galaxy, to make it easly accessible to the scientific community, in easy-to-use way....
#14071 : MacSyFinder 2.0
MacSyFinder is a framework to model and detect macromolecular systems in genomes using decision rules (gene content and architecture) and similarity searches (protein profiles). It was initially developed at GEM by Sophie Abby with the help of Bertrand Néron and Hervé Ménager. The generic program - MacSyFinder - and its associated tools developed subsequently (i.e., CapsuleFinder, CasFinder, CONJscan, TXSScan) were pivotal in several recent analyses performed and published by our unit (Per...
#13980 : MLST versus Short Tandem repeats (Microsatellites) for Pneumocystis jirovecii genotyping
Comparison of Microsatellites and Multi Locus Sequences Typing approaches. Fungi: Pneumocytis jirovecii...
#13848 : Secretome Analysis of OIS IL6KO SASP
Cellular senescence is a stable cell cycle arrest that can be triggered by various biological stresses. Importantly, senescent cells remain metabolically active and secrete numerous molecules, such as cytokines, chemokines, proteases and growth factors. This secretome is called SASP (senescence associated secretory phenotype). Senescence plays a role in several processes, most notably in cancer, where it acts as an intrinsic tumor suppressor mechanism by inhibiting cell growth of premaligna...
#13699 : DNMT and RNMT in Leishmania
We tested DNMT and RNMT inhibitors on Leishmania parasites survival and would like to know which could be the potential targets....
#13672 : Impact of APC gene mutations on anti-tumoral immune responses
The aim of this project is to understand how inherited APC gene mutations affect the immune system of familial adenomatous polyposis patients, and to evaluate the potential contribution of altered immune responses to polyposis and intestinal cancer development in these patients. (see https://research.pasteur.fr/en/project/projet-de-recherche-clinique-impact-des-mutations-du-gene-apc-adenomatous-polyposis-coli-dans-les-reponses-immunes-anti-tumorales/)...
#13654 : Role of Tunneling nanotubes in Glioblastoma
Glioblastoma cells interconnect forming a functional and resistant network. We are investigating the role of these connections in the cancer relapse and treatment-resistance...
#13522 : CRISPR design tools on crispr.pasteur.fr
We would like to add activity prediction and other design tools for guide RNAs on crispr.pasteur.fr...
#13496 : Microscystis transcriptome
The litterature examine mostly the basic metabolism of this photosynthetic organism that forms toxic bloom worldwide. Previously, Straub et al (2011) demonstrated the differential expression of the natural products of Microcystis in function of the day/night rythm, and more recently, we observed even changes in the metabolic profile of several Microcystis involved in intraspecific interactions (Briand et al., 2016). Here, we explore the expression of the genes dedicated to natural products in th...
#13471 : Bioinformatic analysis of paired alpha and beta T cell receptor sequences obtained at the single cell level by illumina sequencing
The rare patients who spontaneously control HIV replication in the absence of therapy show signs of a particularly efficient T cell response. We aim at characterizing the molecular determinants underlying this efficient antiviral response. We have previously shown that CD4+ T cells from HIV controllers express T cell receptors (TCRs) of particularly high affinity for Gag peptides/ MHC II complexes. Furthermore, HIV controllers shared Gag-specific TCR clonotypes at higher frequencies than treate...
#13458 : Assessing the role of gut microbiota in spondyloarthritis patients and impact of anti-TNF treament on its composition
Our hypothesis is that gut microbiota could define predictive markers of response and tolerance to biologics. A. Preliminary results: gut bacteria predicting response to TNF blockers. A proof-of-concept study has been performed on 58 patients who were recruited according to the following criteria: active disease despite NSAIDs intake; no history of inflammatory bowel disease; no antibiotics intake within 3 months prior recruitment. Bacterial 16S rRNA gene sequencing region was performed on...
#13429 : Uncovering diversity and improving gene annotation of Leptospira sppo
Leptospirosis is an emerging zoonotic disease, with high prevalence in tropical regions. It affects both wild and domestic animals, as well as humans, and it is disseminated by asymptomatic carriers, such as rats and mice, that contaminate water with urine. Its etiological agents are some species of the genus Leptospira, member of the phylum Spirochaetes, which are able to colonize hosts through skin injuries or mucous membranes. Once inside the host, the bacteria is able to disseminate quickly ...
#13426 : ICARE
We are interested in Spondyloarthritis. Spondyloarthritis is a chronic inflammatory rheumatism. Currently 2 biologic treatments are available : anti TNF and anti IL-17A. We are analyzing how these treatments modify the immune system of the patients. The goal of this part of the project is to describe how biologics treatments in Spondyloarthritis modifiy the frequence of immune cell populations....
#13412 : Analysis of the clinical manifestations of Lyme borreliosis in France from 2003 to 2011
Lyme borreliosis (LB) is an important tick-borne disease which can cause a broad range of symptoms mainly affecting the skin, the nervous system and the joints. It is caused by bacteria of the Borrelia burgdorferi sensu lato (s.l.) complex. In Europe, at least five genospecies are known to be pathogenic, namely Borrelia afzelii, Borrelia garinii, B. burgdorferi sensu stricto, Borrelia spielmanii and Borrelia bavariensis. In order to assess the health burden, data on the incidence of all the diff...
#13408 : Proteome remodeling induces by the Cytotoxic Necrotizing Factors 1
Urinary Tract Infections (UTIs) represent approximatively 150 to 250 million cases per year, thus are of major public health concern. 80% of community-acquired UTIs are caused by UPECs and about 40% of UPECs are known to produce the Cytotoxic Necrotizing Factors1 (CNF1). The CNF1 is a Rho-activating toxin that catalyzes a specific deamidation of a glutamine of Rho GTPases for cells invasion. The deamidation maintains the GTPases constitutively activated and the constant activation of RhoGTPases ...
#13406 : Multiparametric immunophenotyping of whole blood in IFN-treated multiple sclerosis patients
Adaptive immune cells play important role in pathogenesis of multiple sclerosis by infiltrating the central nervous system, thereby contributing to demyelination and maintenance of an inflammatory microenvironment. In particular, autoreactive T cells, CD4+ T helper and CD8+ T cells exert a detrimental effect, while CD4+ regulatory T cells (Treg) have impaired suppressive function. Interferon b (IFNb), a commonly prescribed treatment for relapsing-remitting multiple sclerosis (RR-MS) decreases re...
#13401 : Identification of mouse skin macrophage subpopulations
The global aim of the project is to characterize and explore the role of dermal macrophage populations in the control of vascular integrity in health and diseases. Currently, we are limited by the lack of population-specific markers that would allow us to study them down to the molecular level. We thus propose to perform a single cell gene expression analysis on pan leukocytes (CD45+) isolated from mouse skin dermis and epidermis in order to identify and define the genetic signature of the stea...
#13393 : Excess calorie intake early in life increases susceptibility to colitis in the adult
Epidemiological data report an association between obesity and inflammatory bowel disease (IBD). Furthermore, animal models demonstrate that maternal high fat diet (HFD) and maternal obesity increase susceptibility to IBD in offsprings. However, the mechanisms that translate maternal obesity and HFD into increased susceptibility to IBD later in life remain unknown. Here we report that excess calorie intake by neonatal mice, as a consequence of maternal HFD, forced feeding of neonates or low litt...
#13391 : Finding SNPs associated with Dengue infection in the mosquito Aedes aegypti
Our research team recently identified an Aedes aegypti mosquito population that is partially resistant to dengue virus infection. We also have candidate genes that potentially innerly this phenotype. In this project, we would like to test wether specific SNPs are associated with virus infection in those mosquitoes. Sequencing data has already been generated with the Omics platform and handled by C3BI....
#13387 : Distribution of Cytotoxic necrotizing factor 1 among the sequence type 131 emergent multidrug resistant lineage of Escherichia coli
E. coli sequence type 131 is primarily responsible for 40-80% of extended-spectrum beta-lactamase (ESBL) infections causing million antimicrobial resistant infections annually. Population genetic analyses indicate that ST131 consists of three different sublineages, clade A, B and C, genetically defined by polymorphisms in the gene fimH (fimH41, H22 and H30, respectively). The Cytotoxic necrotizing factor 1 (CNF1) is one major Uropathogenic E. coli (UPEC) virulence factor that catalyzes a pro-onc...
#13382 : Mechanisms of HIV-1-infected cells susceptibility to Fc effector functions
Deconvolution of the polyclonal antibody response targeting HIV-1 allowed the identification of broadly neutralizing monoclonal antibodies (bNAbs) targeting the viral envelope. Infusion of bNAbs protects against HIV-1 acquisition and decreases viral load. bNAbs kill HIV-1-infected cells, modulate host immune responses, and, when associated to latency-reversal agents, delay viral rebound in animal models. These antiviral activities are mediated by the Fc region, which is required for optimal in v...
#13376 : Antiviral activities of anti-HIV-1 antibodies
Despite the success of anti-retroviral therapy (ART) to treat HIV-1-infected individuals, the persistence of a viral reservoir remains an obstacle to a cure. Characterization of the antibody repertoire in patients led to the identification of broadly neutralizing antibodies (bNAbs) targeting the viral envelope glycoproteins and suppressing HIV-1 infectivity with unprecedented potency. Passive administration of bNAbs in animal models or in infected humans revealed their capacity to decrease viral...
#13341 : Serpentine: a flexible 2D binning method for differential Hi-C analysis
Hi-C contact maps reflect the relative contact frequencies between pairs of genomic loci, quantified through deep-sequencing. Differential analyses of these maps facilitate downstream biological interpretations. However, the multi-fractal nature of the DNA polymer inside the cellular envelope results in frequency values spanning several orders of magnitude: contacts involving loci pairs at large genomic distance are much sparser compared to closer pairs. The sa...
#13324 : Defining the differential contributions of CD4+ and CD8+ anti-CD19 CAR T cells to tumor outcome, immune recruitment and toxicity
Gene-modified T cells expressing a chimeric antigen receptor (CAR) targeting the CD19 molecule have demonstrated promising clinical efficacy in the treatment of B cell malignancies. However, the frequent relapses and toxic adverse events such as cytokine release syndrome represent hurdles to the success of CAR T cell therapies. In most clinical settings, CAR T cells are generated from a mixture of autologous CD4+ and CD8+ T cells before being infused into patients. This inter-patient heterogenei...
#13305 : Characterization of the bacterial and fungal microbiota in Aedes aegypti natural breeding sites and larvae
Although the microbiota of mosquitoes is known to play an important role in their vectorial capacity for human pathogens, most earlier studies have focused on mosquito-bacteria interactions at the adult stage. Mosquitoes are holometabolous insects whose larvae develop in aquatic habitats, whereas the adults are terrestrial. Larval and adult stages are not independent from each other because the larval environment can influence adult life-history traits through carry-over effects. We recently pro...
#13296 : Quality controls for human plasmas and serums stored in biobanks
The quality of the samples stored in biolocial resources centers is a real concern at the international level. Recent scientific publications highlighted difficulties for reproducing published scientific results which constitute a brake to consequent developpment of medical applications.. The quality of the samples used in experiments may partly explain those difficulties. Within the ICAReB platform, samples dating from 1950 are conserved. The question of their quality and usability is posed. ...
#13292 : The anti-IgE antibody Omalizumab induces adverse reactions through engagement of Fc gamma receptors
The therapeutic anti-IgE antibody Omalizumab is used for the treatment of severe asthma, and is known to trigger anaphylaxis in some patients. Since Omalizumab is a humanized IgG1, so we hypothesized that Omalizumab could trigger anaphylaxis through the alternative FcgR-mediated pathway. Indeed, we observed that Omalizumab can trigger anaphylaxis in genetically modified mice expressing human FcgRs. We further produced a mutant version of Omalizumab which can still block IgE but cannot bind FcgRs...
#13287 : Targetting the function of a hypothetical protein
We want to determine the function of a protein conserved among certain phages. Homology searches yield about a hundred hits that clearly share some motifs, however they remain 'putative', without an assigned function. Searching for known motifs doesn't give any hits neither. We would like to use a database of C3BI dedicated to viral proteins to find a possible clue about the protein's role....
#13267 : Analysis of Internal Deletions in EV71
We passaged EV71 in cell culture, followed by RNAseq analysis. The sequences were analysed for the presence of internal deletions within the viral genome. Such deletions can contribute to non-homologous and homologous recombination within Enteroviruses, which can have positive effects, such as the purging of deleterious mutations or to overcome host restrictions. On the other hand such deletions could result in the formation of defective interfering particles (DIs), which have the ability to int...
#13264 : maintenance du site de la Collection des cyanobactéries
mise à jour suite à modification du lien du catalogue CRBIP...
#13260 : Heterogeneity of the skeletal muscle microenvironment
This projects aims at characterizing at the single cell level the stromal microenvironment of the skeletal muscle, to get a better insight into the heterogeneity and function of different cell populations involved in skeletal muscle homeostasis and regeneration....
#13259 : Defective interfering viral genomes of shrimps' viruses
This project to characterize defective viral genomes of shrimp pathogens i.e. Yellow head virus (YHV) from next-generation sequencing of viral RNAs data by using DI-tector or similar tools. NGS data are already available for analysis. We are looking for someone interested in virology in general and more precisely the complexity of viral genomes....
#13205 : Optimisation of freeze and conservation method of peripherical blood mononucleated cells
The provision of human biological material collected, processed and stored under optimal conditions is crucial to ensure the quality of research carried out downstream. These optimal conditions must be determined by a rational method validation approach taking into account the critical parameters of the different biological sample management processes that are likely to have an impact on their quality....
#13204 : Early transcriptional signature of T-cell memory after dengue vaccination
Dengue virus (DENV) induces strong T and B cell responses upon infection. However, there is currently neither vaccine nor specific treatment against DENV, which is spreading worldwide causing 400 million new infections every year, of which 100 million cases are symptomatic, ranging from a self-limiting febrile illness named dengue fever (DF) to more severe life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). One of the major obstacles of dengue vaccine development i...
#13196 : Chikungunya virus adaptation to a low temperature in a French population Ae. albopictus
The chikungunya virus (CHIKV) is an emerging mosquito-borne virus which has widely spread around the world in the last two decades. The virus is transmitted between human hosts by Aedes mosquitoes, including Aedes albopictus which is now established in more than 51 departments in France. The transmissibility of CHIKV can be affected by a combination of both intrinsic and extrinsic factors. Since mosquitoes are poikilothermic insects, environmental temperature is of particular importance. Indeed,...
#13174 : Characterization of Yolk Sac Derived Progenitors in the Fetal Liver
Erythromyeloid progenitors (EMPs) originate from the yolk sac during early mouse development and migrate to the fetal liver via the circulation where they undergo massive expansion and differentiation into hematopoietic lineages. These events occur prior to the intraembryonic emergence of hematopoietic stem cells (HSCs). Unlike HSCs, EMPs cannot give rise to lymphoid lineages, nor can they provide long-term repopulation. As such, they are considered a transient fetal population, yet it is EMP-de...
#13146 : Intégration d'outils bioinformatique dans Galaxy pour identification bactérienne
Intégration d'outils bio-informatique dans Galaxy pour identification bactérienne...
#13141 : 3D PATH
Complex chronic diseases are caused by the accumulation of genetic, microbial and lifestyle factors. The number and complexity of such factors makes prediction of pathogenesis and therapy particularly difficult. Although a single factor is rarely sufficient to trigger pathology, genetic and environmental factors have so far been studied in isolation. Nevertheless, a substantial number of genetic variants have been associated with disease risk and the concomitant lifestyle shift and excessive hyg...
#13128 : Remettre les servers Genolist comme LegioList, TuberclListe, Colibri etc en service
The servers like LegioList are used by my group and many groups around the world working on Legionella pathogenesis since its establishment in 2004. This server has provided us with an important reserach tool and valuable information for research and is providing Institut Pasteur with international visibility...
#13125 : Move of the DISCO-BAC server VM to the new DSI infrastructure
DISCO-Bac (http://disco-bac.web.pasteur.fr/), a Web server, is a part of a recent publication https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-3932-y (Co-authored by former Hub member Olivia Doppelt-Azoueral, who conceived and implemented the DISCO-BAC database and its sophisticated interface). The main result of the paper is to show the widespread existence small peptides across prokaryotes, the predictions being accessible, along with context information, through DISCO-BAC. ...
#13116 : Targeted search of specific commensals in 16S databases
Bacteria analysis of fecal samples by 16S sequencing has provided a wealth of information for the distribution of bacterial species in both health and disease conditions. When looking at bacterial composition, the focus in generally put on the presence or absence of the most abundant species; yet, even low abundant species may have significant effects on the host when present at even low abundance. To assess the possible contribution of low abundance bacterial species, we aim to undertake a tar...
#13081 : Hamper cell-to-cell variation to enhance drug-mediated killing
Without new treatment development tuberculosis could cause about 70 million deaths by 2050, mostly due to the spread of multidrug-resistant strains. The standard drug regimen still builds on the first drugs introduced decades ago, and takes 6 months in the case of drug-sensitive tuberculosis, and up to 2 years in the case of drug-resistant tuberculosis, with heavy side effects. This long therapeutic regimen often results in patients not being able to follow it or complete it correctly, which pro...
#13078 : Determination of the transcriptome controlled by the two-component system BvrR/BvrS using dominant positive and negative BvrR mutants
Our project is focused on the intracellular life of Brucella abortus, the causative agent of bovine brucellosis. B. abortus is a facultative extracellular-intracellular pathogen that upon infection of its mammalian host, invades professional phagocytes in which the bacterium transits into the Brucella-containing vacuole and reaches its replicative niche, the endoplasmic reticulum (ER). A key element required for B. abortus intracellular replication is the BvrR/BvrS two-component system. Previous...
#13043 : Build a software to decipher Gephyrin alternative transcripts obtained with long read sequencing
Disruption of GABAergic inhibitory circuits is one of the common alteration responsible for several psychiatric developmental disorders. Gephyrin (GPHN) is the common and main molecular organizer of inhibitory synapses. It acts as a hub under the postsynaptic membrane for the multiple protein-protein interactions. Intriguingly, inhibitory synapses are highly heterogeneous, bearing various inhibitory postsynaptic potential (IPSP) properties and also specific subcellular localization on their targ...
#12997 : Identifying subpopulation-specific signatures of tuberculosis persistence for enhanced diagnostics.
Microbes are prone to rapid changes and they can either exploit or countervail their variation in a context-dependent manner. To this purpose, both genetic diversity and non-genetic phenotypic variation exist. However, while the overall mutational evolution occurs over lengthy timescales, epigenetic changes take place on a large scale and more rapidly. Collectively this implies that the diversity we observe is profoundly driven by non-genetic variation. This is particularly relevant for the WHO ...
#12996 : Analyse transcriptionnelle du cellules cancéreuse intestinal vs normales après co-culture avec la bactérie associée au cancer Streptococcus gallolyticus
Streptococcus gallolyticus sous espèce gallolyticus, autrefois dénommée Streptococcus bovis biotype I, est une bactérie de la flore intestinale qui constitue une cause émergente de septicémies et d’endocardites chez les personnes âgées. Depuis plus de 50 ans, les études épidémiologiques indiquent l’existence d’une forte association entre les infections invasives à S. gallolyticus et le CCR (cancer colorectal) (Pasquereau-Kotula et al., 2018). Néanmoins, le rôle exact de S.gal...
#12992 : Genomic DNA sequencing of Burkholderia ambifaria Q53 strain isolated from peanut rizospheric soil
Burkholderia ambifaria bacteria are uiquituos microorganisms present in different environmental sources. Particularly these bacteria have been found to be frequently isolated from rhizospheric soils of a wide variety of plants. Burkholderia bacteria have been proved to be benificial to the plants by improving their growth trough different mechanisms. The B. ambifaria Q53 strain was isolated from the rizosphere of peanut (Arachis hypogaea L.). This leguminous plant is a very important crop in man...
#12991 : Role of RNA primary and secondary structure in non-homologous recombination
Enteroviruses are known to recombine a lot during the replication cycle. A lot of viruses produce defective genomes, which are generated by the polymerase skipping several nucleotides and thus, forming internal deletions of the genome. We would like to look at this process more closely and come up with a model, which includes the role of the RNA virus genome itself, including its structure....
#12988 : LGP2 binds PACT to regulate RIG-I- and MDA5-mediated antiviral response
We need an independent statistician to confirm that appropriate statistical tests were used to analyze the data in your manuscript for the final revision of our manuscript in Science Signaling (Manuscript Number: aar3993, \"LGP2 binds PACT to regulate RIG-I- and MDA5-mediated antiviral response\" ). Sincerely yours, Anastassia Komarova...
#12987 : Afribiota-Neuro
Globally one out of four children under 5 years is affected by linear growth delay (stunting). This syndrome has severe long-term sequelae including increased risk of illness and mortality and delayed psychomotor development. Stunting is a syndrome that is linked to poor nutrition and repeated infections. To date, the treatment of stunted children is challenging as the underlying etiology and pathophysiological mechanisms remain elusive. We hypothesize that pediatric environmental enteropathy (P...
#12963 : Gene expression and its regulation during and after inpatient detoxification of cocaine: a link to relapse?
Cocaine is the most widely used illicit stimulant in Europe1, with a recent increase in use in the French general population. Cocaine addiction (CocAdd) is recognised as a public health priority worldwide, affecting 3% of the US general population, with high burden for individuals and societies1 (4 to 8-fold increase in standardised mortality rates). Clinically, (cocaine) addiction (or substance use disorder) is defined as the compulsive use of a substance causing clinically and functionally sig...
#12929 : Single nucleotide polymorphisms and genome organization in members of the genus Yersinia
Members of the genus Yersinia include environmental as well as pathogenic bacteria. Pathogenic species (Y. pestis, Y. pseudotuberculosis and Y. enterocolitica) have historically been targets for research aimed at understanding how bacteria evolve into diverse mammalian pathogens. The advent of large-scale population genomic studies has greatly accelerated the progress in this field, revealing how gene gain, gene loss and genome rearrangement events have impacted evolution of enteropathogenic bac...
#12920 : Séquençage à haut débit (NGS) et traitement de séquences ADN des domaines variables d’anticorps simple chaine d’alpaga (domaines VHH ou Nanobodies®)
Dans notre laboratoire nous nous intéressons à la conception et construction de banques d’anticorps simple chaine issus du répertoire immunitaire des alpagas. Ces banques immunes, sont constituées d’un million de séquences ADN différentes codant pour les domaines variables des anticorps simple chaine spécifiques d’une protéine cible donnée, plus communément appelés domaines VHH ou Nanobodies®. Nous souhaitons à présent caractériser ces banques crées au laboratoire par sé...
#12913 : Genetic and statistical analysis of data produced with the Collaborative Cross at the Institut Pasteur
The project aims at developing (1) a database dedicated to the storage and statistical analysis of Collaborative Cross based data and (2) implement genetic analysis tools based on rqtl2 for the identification of QTL on this data....
- Pascal CAMPAGNE
- Vincent GUILLEMOT
- Rachel TORCHET + 1 operator
#12901 : crispr.pasteur.fr
crispr.pasteur.fr is a website providing resources to visualize CRISPR screen data and design CRISPR experiments in bacteria...
#12897 : Comparative genomics of Listeria monocytogenes isolates
There exists a broad biodiversity inside the Listeria monocytogenes species, which can be summarized by the existence of evolutionary lineages and more than 100 clonal complexes (CCs or clones) based on core genome multilocus sequence typing (cgMLST), which are geographically and temporally widespread. We aim to link genomic markers to temporal, geographical and sampling origin in order to better understand the ecology and evolution of Listeria monocytogenes....
#12891 : Identification d’une mémoire épigénomique à Streptococcus pneumoniae
Les modifications de la chromatine, au niveau de l’ADN ou des histones, jouent un rôle fondamental dans la régulation de l’expression des gènes chez les eucaryotes, en contrôlant l’accès de la machinerie transcriptionnelle aux séquences promotrices. Des études récentes ont mis en évidence que modifier la chromatine est l’un des moyens par lesquels les bactéries pathogènes interfèrent avec le programme transcriptionnel des cellules hôtes. Cependant, les mécanismes moléculai...
- Claudia CHICA
- Rachel LEGENDRE
- Adrien PAIN + 1 operator
#12853 : Impact des contraintes biomécanistiques sur la dynamique des macro-ouverture induits par l'EDIN de Staphylococcus aureus.
Several bacterial pathogens compromise the barrier function of endothelia by triggering the opening of transendothelial cell macroaperture (TEM) tunnels as large as several micrometres in width. This phenomenon has been linked to the dissemination of Staphylococcus aureus via the haematogenous route. The opening of TEMs occurs in response to the overall relaxation of the actomyosin cytoskeleton and cell spreading-associated with a disruption of focal adhesions via either toxin-induced inhibition...
#12833 : Training project for bacterial ChIP-seq Analysis on Streptococcus agalactiae
Streptococcus agalactiae (GBS) is a commensal gram-positive bacteria which asymptomatically colonize the genital and intestinal tract of healthy women. However, GBS is the leading cause of bacterial invasive infections in newborns in developed countries. The ability of GBS to succeed both as a commensal and a pathogen relies on a highly dynamic regulation of colonization and virulence related genes. The major regulator identified to date is the two-component system CovSR (Control of Virulence ...
#12775 : Determination of host response elicited by different Salmonella lifestyles
A number of mammalian cell types are susceptible to Salmonella Typhimurium infection, including epithelial cells, fibroblasts and macrophages. It has recently been demonstrated that Salmonella display specific lifestyles in a host cell type-specific manner, where these lifestyles are remarkable for the subcellular localization and replication rate of Salmonella. During epithelial cells infection, Salmonella are first uptaken by the host cell and being encapsulated in a unique endocytic compa...
#12771 : Tissue-resident stromal cell heterogeneity
Stromal cells are essential during organ morphogenesis and for the maintenance of tissue homeostasis. In addition, increasing evidence indicates that stromal cells play a role in certain type of chronic diseases, such as cancer. In this project, we will investigate stromal cell heterogeneity at the single cell level in specific organs at homeostasis and during pathology....
#12767 : Comparative genomics of Helicobacter pylori bismuth resistant strains
Helicobacter pylori is a Gram-negative pathogen whose infection results in various gastric diseases including gastric cancer in Humans. Current drug therapy against the bacteria involves a combination of two antibiotics, proton-pump inhibitor and a Bismuth salt. Introduction of bismuth has resulted in increased success rate compared to traditional therapies without bismuth salt. H. pylori is a genetically variable bacteria with high rates of mutations and recombination. Interestingly till now, t...
#12765 : Viral Host Range Databank
Bacteriophages infect bacteria. One bacteriophage can infect several strains. Around the world, many labs have performed spot tests to determine the host range of bacteriophages but this information is not accessible because there is no tool to process and store it. Developing such a tool will be useful for the phage community but also for the entire community of virologists....
#12674 : DNMT orthologs in Leishmania
Looking for DNMT (DNA methyltransferase) orthologs in Leishmania which could be potential targets of epigenetic inhibitors active against the parasite....
#12670 : Genome-wide interactions between HP1g 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, HP1g has been shown to localize within the body of coding genes in correlation with their transcriptional activity. We have identified funct...
#12647 : Sequence analysis of Mycobacterium marinum mutants
Nous souhaitons analyser les séquences de sept mutant de Mycobacterium marinum générées par l’utilisation de concentrations croissante d’un antibiotique candidat dont nous ne connaissons pas la cible. Avec ces mutants, nous essayons de connaître la cible de ce composé....
#12641 : Functional interactomics of SKAP2
The SRC Kinase Adaptor Phosphoprotein 2 (SKAP2), a broadly expressed protein with some higher expression in haematological lineages recruiting protein partners to specific subcellular domains, plays a central role in multiple physiological processes in relation with cell migration. We have linked this gene in interaction with CNTNAP5 to susceptibility to Dengue Shock Syndrome in a cohort of Vietnamese patients. By coupling a yeast-two-hybrid screen with a luciferase complementation assay and mut...
#12627 : Role of small non coding RNAs in the adaptive response to oxidative stress in pathogenic Leptospira
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. Leptos...
#12619 : Asymptomatic pathogen carriage in stunted and non-stunted children living in Antananarivo, Madagascar
This project is integrated in the analysis of the gut ecosystem of children implicated in the AFRIBIOTA project, a translational project performed within a consortium of researchers and medical doctors from the Central African Republic, Madagascar, France and Canada (see https://research.pasteur.fr/fr/program_project/the-afribiota-project/). AFRIBIOTA aims at understanding the risk factors and pathophysiological changes underlying chronic child malnutrition as manifested through delayed growth. ...
#12618 : Cellular plasticity during mammary gland development
The development of the mammary gland occurs in five distinct phases: embryogenesis, puberty, pregnancy, lactation, and involution. Due to its extraordinary regenerative capacity, the mammary epithelium is a fantastic system to study the physiological regulation of cellular plasticity in vivo. It comprises two major cellular lineages, the outer myoepithelial (also called basal) and inner luminal cell layers. Although the existence of post-natal bipotent mammary stem cells (MaSCs) remains debatabl...
#12591 : Rainfalls and water contamination in Antananarivo over 25 years
Concerns are growing over urban drinking-water quality due to an inefficient management infrastructure in most low-income countries. Outbreaks of waterborne were linked to extreme climatic events, despite that the causal relationship between change on rainfall patterns, temperature rise and drinking water microbial quality is complex, involving an interplay of the type of water supply, water source and water treatment technology. Antananarivo, the capital of Madagascar is witnessing rapid urbani...
#12571 : Role of the Topoisomerase 1 and Guanine quadruplexes as transcriptional regulators
DNA Topoisomerase 1 (Top1) is a major regulator of gene expression with great impact on genome stability. Similarly, Guanine quadruplexes (G4) have recently emerged as critical elements for transcription regulation and potential threats to the genome integrity. Studies of Top1 and G4 have many medical implications since their mutations or deregulations are associated with several pathologies, such as cancers, neurodegenerative diseases or viral infections. A few studies, including ours, have re...
#12502 : Toxin induced dephosphorylation of H3S10
During infection with bacteria, secretion of toxin induces histone modifications in the host cell. One such modification is dephosphorylation of histone H3 on serine 10. We have characterized this modification and the bacterial factors that are important for inducing it. The bacterial toxin listeriolysin O is one such factor. However the role of this modification is unknown. Genome wide analysis of the genes or genetic regions marked with dephosphorylated H3 will help us reveal the function of ...
#12497 : Genome annotation of sequenced bacteria of the Culture Collection of the Pasteur Institut
The CRBIP, Centre de Ressources Biologiques de l’Institut Pasteur, is a structure created in 2001 that encompasses the Pasteurian culture collections: the CIP (bacteria collection), the PCC (cyanobacteria collection), the ICAReB (human samples collection) and the Eukaryotic virus collection. Since January 2016, the CIP, has sequenced more than a thousand bacterial genomes and assembled them using the P2M pipeline. An initiative has been proposed by the CRBIP, in line with its new strategy of v...
#12401 : Comparison of matrices of antibody gene usage
Our goal is to have a bioinformatic tool that performs the 2 x 2 comparison of matrices of numbers in matrix batches. Each matrix corresponds to the use of gene fragments (V or J) to create a re-arranged gene (VJ) encoding a specific antibody, identified by droplet microfluidic or flow cytometry techniques followed by high throughput sequencing (NGS). ). The matrices are made for the two chains encoding the specificity of an antibody: the heavy chain (VH) or the light chain (VL). The goal is to ...
#12288 : High content screening of mitochondrial morphology defects in mitochondrial genetic diseases
Mitochondria are double-membrane bound organelles that are essential in every tissue of the body. They are metabolic hubs and signalling platforms that are deeply integrated into cellular homeostasis. The functions of mitochondria are intimately linked to their form, which is regulated by a balance of membrane fusion and fission: dynamin-like GTPases OPA1 and MFN1/2 perform membrane fusion and DRP1 regulates membrane fission. Mutations in mitochondrial genes cause a pleiotropic spectrum of cli...
#12261 : Identification of eukaryotic 5'UTRs
Identification of alternative 5'UTR in an eukaryotic transcripts...
#12260 : Pasteur MLST: Institut Pasteur genomic taxonomy database of microbial strains
- The Institut Pasteur genomic taxonomy database of microbial strains (“Pasteur MLST”) is a free, publicly-accessible resource that hosts nucleotide sequence-based definitions of microbial strains, along with information on bacterial isolates (provenance data) and their genomic sequences. The Pasteur MLST database provides universal nomenclatures that are largely adopted for important pathogens (Klebsiella, Listeria, …), and represent a unifying language on strains for microbial population...
#12257 : Analysis of neuronal population dynamics in rodents during virtual navigation
To study the neuronal mechanisms underlying the generation of distinct memories, it is necessary to perform experiments in which the sensory elements of the environment are under the precise control of the experimenter. To achieve this goal, we have developed a virtual-reality environment for rodents that we combine with imaging and electrophysiological methods to record the activity of individual neurons and populations of neurons while the animals are navigating in virtual reality. This system...
#12246 : functional enrichment of RNA processing factors associated with proteins of influenza viruses
A protein-protein interaction screen has been done beween viral proteins of influenza A viruses and a library of about 100 human factors invovled in RNA processing through RNA exonucleases activity. 20 factors were identified as interactors of viral proteins. To see if this targeting corresponds to specific RNA metabolism focntions of the cell, we analysed using Cytoscape the first neighbors of these factors in the human ORFeome. We then compared using the ClueGo pluging the functional enrichme...
#12231 : Identification of immune response signatures that correlate with therapeutic responses to TNF inhibitors using machine-learning algorithms
Anti-TNF therapy has revolutionized treatment of many chronic inflammatory diseases, including rheumatoid arthritis, Crohn’s disease and spondyloarthritis (SpA). However, clinical efficacy of TNF-inhibitors (TNFi) is limited by a high rate of non-responsiveness (30-40%) both in SpA and other diseases, exposing a substantial fraction of patients to important side-effects without any clinical benefit. Despite the extensive use of TNFi since many years, it is still not possible to determine which...
#12220 : The Flemmingsome: the proteome of intact cytokinetic midbodies
The central part of the intercellular bridge connecting the two daughter cells during cytokinesis is a highly dense structure named the Midbody first described by Flemming in 1891. Work in the past ten years revealed that the midbody is a platform that concentrates essential proteins involved in cytokinetic abscission. After abscission, the midbody is cut on both sides, thus generating a midbody remnant (named MBR). The MBR usually interacts with the cell surface of one of the two daughter cells...
#12193 : Automated merging of CSV documents.
We want to automatize the merging of CSV document for data analysis purposes. We've already discussed it with Gael Millot....
#12128 : Transcriptomics of Anopheles – Plasmodium vivax interactions towards identification of malaria transmission blocking targets
Despite the worldwide importance of malaria due to Plasmodium vivax, there is currently almost no data on the molecular responses of the Anopheles mosquito vectors to this parasite species. Understanding these responses will contribute to identify relevant strategies to interrupt the transmission of P. vivax by targeting the mosquito vector. Such approaches are urgently needed, as P. vivax is difficult to target on the long term in humans as a consequence of the hypnozoite stage that is res...
#12107 : Ecological evolution in Klebsiella
In this project we study ecological diversification of Klebsiella pneumoniae and closely related species. Using comparative genomics we want to identify the pattern of genome adaptation to different environments...
#12106 : An Aedes albopictus-driven epidemiological prediction for arboviral diseases outbreak in Europe
As a result of combined climate change and globalization (increased flow of travelers and goods), the distribution of the mosquito Aedes albopictus is expanding significantly outside tropical regions. Ae. albopictus has already established stable colonies in 20 European countries (https://ecdc.europa.eu/en/publications-data/aedes-albopictus-current-known-distribution-june-2018). Being the main mosquito that can be incriminated in the transmission of chikungunya, dengue, and zika viruses in E...
#12069 : Heterogeneity of tissue resident stromal cells
Tissue resident stromal cells form the scaffold of all organs. In addition, they provide signals for proper positioning, survival and interaction of a number of other cell types, such as immune cells. Following tissue damage, the stromal microenvironment play an esssential role to organize inflammation and tissue repair. The stromal vascular fraction (SVF) of most organs is composed of immune cells, endothelial cells, mesenchymal stromal cells and tissue stem cells. Our lab investigates the impa...
#12068 : Antimalarial drug resistance in Africa: A comprehensive molecular analysis of the emergence of artemisinin resistant parasites in Africa
We are involved, in collboration with the WHO, in the SaMARA which aims at detecting the emergence of antimalarial drug resistance in Africa. Samples (dried blood spots) are collected from the Nantional Malaria Control Programmes in Africa during clinical efficacy studies. My group at the Institut Pasteur in collaboration with the Institut Cochin (Frédéric Ariey) tested these samples and assessed the proportion of parasites harboring SNPs or CNV associated to antimalarial drug resistance. We...
#12049 : Understanding the pathways of small RNA production during Meiotic Silencing by Unpaired DNA (MSUD) in the fungus Neurospora crassa
The canonical (“textbook”) process of DNA homology search and recognition is initiated by DNA double-strand breaks and is mediated by the universally conserved recombinases of the RecA family. Using the phenomenon “Repeat Induced Point mutation” (RIP) in N. crassa as a model system, we have previously revealed the existence of another way to search for DNA homology, which does not require RecA proteins and which apparently operates on intact DNA double helices. This pathway can be extrem...
#12041 : Characterization of Yolk Sac Derived Progenitors in the Fetal Liver
Erythromyeloid progenitors (EMPs) originate from the yolk sac during early mouse development and migrate to the fetal liver via the circulation where they undergo massive expansion and differentiation into hematopoietic lineages. These events occur prior to the intraembryonic emergence of hematopoietic stem cells (HSCs). Unlike HSCs, EMPs cannot give rise to lymphoid lineages, nor can they provide long-term repopulation. As such, they are considered a transient fetal population, yet it is EMP-de...
#12018 : Assessing the integrations of viral sequences into the genomes of Aedes albopictus and Aedes aegypti
Aedes albopictus is an important vector for transmitting arboviruses, such as Dengue, Chikungunya, West Nile or Zika viruses. Its worldwide distribution due to its high ability to adapt to variable environments makes this species a serious threat. This mosquito also better transmits Chikungunya than Dengue virus, and many studies are still trying to understand the deep relationships between these viruses and their vectors in order to develop new control strategies. Moreover, it is now well kno...
#11988 : Phage infection dynamics in the gut of gnotobiotic mice
Taking advantage of a murine model of controlled microbiota composed of 12 strains, we evaluated the activity of a cocktail of three virulent bacteriophages to target a murine Escherichia coli strain in the mammalian gut....
#11975 : Analyse d’expression de gènes de la réponse immune par voies fonctionnelles
Ce projet a pour but de réaliser une analyse par voies fonctionnelles d’environ 600 gènes impliqués dans la réponse immunitaire chez l’homme avec une attention particulière vis-à-vis des gènes impliqués dans le contrôle de l’inflammation et de l’auto-immunité....
#11966 : Dynamic and integrative multidimensional OMICs analysis of the cellular senescence fate
Cellular senescence is a complex stress response that durable (yet not irreversibly) arrests cell proliferation and is accompanied by widespread changes in chromatin structure, metabolism and gene expression including the production and secretion of a plethora of inflammatory factors. Cellular senescence plays beneficial roles during embryonic development, tissue regeneration, and tumor suppression. Paradoxically, it is also considered a major contributor to aging and age-related diseases, the l...
#11936 : Dissecting Peptidoglycan pathways in human near-haploid cells
It has been found that specific fragments of the peptidoglycan (PG), namely the Muramyl-triDAP (MTP) and Muramyl-dipeptide (MDP) are specifically recognized by the innate immune receptors Nod1 and Nod2, respectively (Girardin, 2003). However, it is still not known how these fragments reach the cytosol after being shed by bacteria. Therefore, the near-haploid human cell line HAP-1 (horizondiscovery;HAPLOGEN) has been transducted with a retroviral construct containing a promoterless GFP that wil...
#11931 : High-throuput nanobodies (VHH) screening and sequencing
Alpacas belong to the family of camelids, which has the peculiarity to produce two kinds of antibodies: conventional antibodies made of heavy and light chains and particular single chain antibodies made of heavy chain only. In these antibodies the antigen recognition domain, called nanobodies or VHH, is monomeric and has the advantage to have high affinity for the antigen and to be smaller and more stable compared to that of conventional antibodies. The gold standard technique to isolate nanobo...
#11885 : 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 tools already exist, such as peptigram and drawmap, they don’t fully fufill our expectations and are not completely appropriate for us. To develop this integrative tool, we propose to use proteomics datasets obtained for the analysis of modified histones as a pilot. This work will then be published...
#11805 : 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 séquence nucléotidique de différents gènes répartis dans le génome (généralement entre 5 et 10). L’Institut Pasteur développe depuis de nombreuses années des schémas MLST pour différentes souches d’intérêt biomédical (e.g. Bordetella, Klebsiella, Listeria, Escherichia, Salm...
#11793 : 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 infections in newborns in developed countries. The ability of GBS to succeed both as a commensal and a pathogen can be linked to its capacity to efficiently colonize the host, while still retaining its toxic capacities for the invasive phase of the infectious process. This highly dynamic regulation relies on...
#11691 : 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 conformational change. Viral fusion proteins are the most well studied and are classified in three different groups: class-I, with a central trimeric alpha-helical coiled coil with the fusion peptide at the N-terminal end; class-II, which are folded as three beta-sheet rich domains with an internal ...
#11681 : 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 ...
#11642 : 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...
#11593 : 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....
#11514 : 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...
#11491 : 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 ...
#11317 : 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...
#11315 : 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...
#11308 : 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...
#11305 : 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...
#11290 : Analyse statistique d'interactions protéine-protéine
Réalisation d'un interactome entre des protéines de mammifères et une protéine bactérienne de virulence....
#11226 : 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...
#11221 : 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...
#11123 : 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...
#11075 : 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...
#11074 : 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...
#10966 : 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....
#10958 : 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...
#10948 : 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...
#10940 : 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...
#10939 : 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...
#10938 : 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...
#10937 : 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....
#10934 : 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...
#10928 : 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...
#10921 : 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...
#10920 : 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...
#10913 : 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...
#10906 : 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 ...
#10896 : 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...
#10895 : 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...
#10893 : 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....
#10841 : 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....
#10840 : 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...
#10825 : 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...
#10791 : 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 ...
#10781 : 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...
#10757 : 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....
#10712 : VCF filtering script
A partir de fichier VCF appliquer un certain nombre de filtre et retourner un fichier VCF...
#10700 : 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...
#10674 : 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....
#10570 : 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,...
#10540 : 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...
#10508 : 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...
#10502 : 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...
#10357 : 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...
#10344 : 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...
#10343 : 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...
#10315 : 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...
#10297 : 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....
#10209 : 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...
#10143 : 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...
#9762 : 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...
#9635 : 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...
#9210 : 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...
#8806 : 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 ...
#8788 : 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...
#8727 : 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 ...
#8657 : 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...
#8565 : 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...
#8543 : 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....
#8528 : 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...
#8521 : 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 ...
#8494 : 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...
#8491 : 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...
#8453 : 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...
#8392 : 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....
#8364 : 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...
#8363 : 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 ...)...
#8340 : 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...
#8328 : 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...
#8318 : 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....
#8302 : 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...
#8290 : 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...
#8263 : 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....
#8239 : INNOV DIAG HPV VALOEXPRESS
Molecular markers of cervix lesions linked to HPV infections....
#8232 : Looking for the SNPs in evolved Corynebacterium diphtheriae genomes
Searching and annotating SNPs in evolved Corynebacterium diphtheriae genomes...
#8227 : 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...
#8217 : 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...
#8202 : 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...
#8130 : 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 tract there are rare, but complex to resolve, cases of E. coli infection of central veinous catheter. To determine whether the E. coli strains that colonize central veinous catheters have specific properties we have started a preliminary project where few E. coli strains responsible for such infect...
#8125 : 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....
#8117 : Histone Methyltransferase and Demethylase in Leishmania
I would like to retrieve all HMT and HDM in Leishmania...
#8094 : 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,...
#8067 : 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...
#8002 : 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...
#8001 : 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...
#7990 : 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...
#7968 : 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....
#7965 : Statistical analysis of PI survey for the scientific direction
Statistical analysis of PI survey for the scientific direction...
#7964 : Identification de SNP entre 2 souches bactériennes
Identification de SNP entre 2 souches bactériennes la souche sauvage et le révertant (Pseudomonas aeruginosa)...
#7930 : 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...
#7917 : Recombination among enteroviruses
Notre objectif est d'étudier comment la recombinaison génétique génère de la diversité au sein des écosystèmes d'entérovirus....
#7901 : 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....
#7841 : 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...
#7836 : 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 ...
#7834 : 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...
#7829 : 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....
#7820 : 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...
- Thomas BIGOT
- Marie-Agnès DILLIES
- Rachel LEGENDRE + 2 operators
#7810 : 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...
#7789 : 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...
#7757 : 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. ...
#7750 : 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...
#7721 : 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 ...
#7704 : 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 ...
#7631 : 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...
#7608 : 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...
#7607 : 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
#7596 : 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...
#7528 : 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...
#7437 : 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,...
#7429 : 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...
#7427 : 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 keywordTool DevelopmentProject organismBacteriaManagerOperators
#7419 : 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....
#7413 : 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...
#7409 : 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...
#7331 : 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....
#7283 : 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 ...
#7277 : 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....
#7213 : 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...
#7198 : Genomic analysis of bacterial evolution
We are interested to look at evolution of bacteria in presence of bacteriophages within the gastrointestinal tract of animals. ...
#7188 : 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...
#7143 : 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 ...
#7142 : 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.
#7121 : Determination of phage termini using NGS
See below ...
#7089 : 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....
#7074 : 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....
#7072 : 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...
#7069 : 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...
#7066 : 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...
#7046 : 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 ...
#6952 : 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....
#6826 : 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...
#6818 : 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...
#6803 : 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...
#6783 : 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...
#6761 : Impact of hepatic inflammation on microbiota
The aim of the project is to search for the effects of hepatic inflammation on microbiota....
#6759 : 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....
#6721 : 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. ...
#6701 : 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...
#6699 : 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...
#6667 : 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....
#6579 : 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...
#6535 : 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 ...
#6510 : 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...
#6333 : 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...
#6325 : 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,...
#6313 : 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....
#6311 : 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...
#6272 : 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....
#6040 : 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....
#5740 : 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...
#5679 : 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 ...
#5667 : 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...
#5583 : 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....
#5567 : Rift valley fever NSm protein functional study
Screening for NSm function in infected mammalian cells by proteomic analysis....
#5489 : Zebrafish microbiota
16S OTU assignment and statistical analysis of zebrafish microbiota in different experimental conditions....
#5412 : 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....
#5310 : 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...
#5121 : 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...
#5034 : 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...
#4863 : 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....
#4711 : 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...
#4541 : 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...
#4489 : 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...
#4336 : 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...
#4173 : 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...
#4109 : 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....
#4108 : 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...
#3936 : 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....
#3907 : 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
#3905 : 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...
#3883 : 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 ...
#3826 : 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...
#3564 : 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...
#3475 : 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...
#3456 : 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...
#3442 : 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...
#3346 : 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...
#3327 : 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...
#3322 : 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...
#3312 : 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. ...
#3257 : 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...
#3255 : 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....
#3254 : 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. ...
#3223 : 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...
#3127 : 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...
#3103 : 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...
#3100 : 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...
#3086 : 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...
#3035 : Immunovax
Analysis of the immune response to yellow fever 17D vaccination...
#3030 : 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...
#2976 : 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...
#2944 : Antibody sequencing by MS: Automation of analysis
Protein sequencing by MS: Automation of analysis...
#2937 : 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....
#2936 : 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. ...
#2933 : Variant effects on influenza virus proteins
Collect statistics on variants found in different strains of influenza virus. Determine variant effects to the protein sequence....
#2922 : 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...
#2920 : Un workflow pour l'analyses des polymorphismes des souches de grippe saisonnier.
analyses et classification des échantillons grippales....
#2919 : 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....
#2918 : 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...
#2917 : 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....
#2905 : 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 ...
#2904 : 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....
#2892 : 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 ...
#2889 : 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...
#2882 : 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...
#2881 : 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)....
#2875 : 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...
#2873 : 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...
#2871 : 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...
#2850 : 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....
#2829 : 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....
#2827 : N/A
N/A...
#2822 : 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...
#2760 : 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...
#2741 : 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...
#2720 : 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...
#2712 : 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....
#2622 : 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
#2598 : 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....
#2596 : 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....
#2595 : 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...
#2561 : 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...
#2552 : 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 ...
#2548 : INNOV DIAG HPV
Molecular markers of cervix lesions linked to HPV infections....
#2535 : 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...
#2533 : Transcriptome analyis of two human T cell subsets
The summary is below. I would prefer to keep it confidential except the tittle...
#2529 : 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...
#2528 : 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...
#2527 : 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,...
#2526 : 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?...
#2525 : Characterization of an unusual Leishmania major HSP70-related protein
WYSIWYG editor...
#2512 : 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...
#2510 : 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...
#2506 : 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...
#2504 : Analyse de données de miRNA
Recherche de cible pour des miRNAs chez l'Humain....
#2497 : 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...
#2490 : 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....
#2485 : 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. ...
#2484 : Genomic analyses of E. coli strains
We are examining differences within the genomes of E. coli strains....
#2479 : 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....
#2456 : 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...
#2436 : 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...
#2426 : 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....
#2418 : 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....
#2417 : 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...
#2416 : 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...
#2409 : 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....
#2405 : 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...
#2391 : 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...
#2318 : 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 in the pathogenic yeast Candida albicans have attempted to identify novel transcription factors that may be associated with regulating antifungal drug tolerance. In order to investigate novel regulators of cell wall permeability and antifungal responses in the pathogenic mold Aspergillus fumigatus, ...
#2314 : 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...
#2309 : 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...
#2303 : 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....
#2294 : 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...
#2286 : 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...
#2277 : Transcriptome of Human sperm
We search for the expressed transcript in mature normal sperm as compared to the infertil one....
#2267 : 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...
#2266 : 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 su