BISTRO

#19319 : Data analysis of protein measurements in patients with multiple sclerosis

A statistical analysis of protein measurements in serum and CSF fluids of patients with multiple sclerosis will be performed in order to find some correlative links...

#19315 : CRISPR antimicrobials

We want to add/create a similar website to CIRPSR.pasteur.fr to use CRISPR-Cas9 as an antimicrobial....

#19310 : Role of microbiota and bacterial cooperation in gastrointestinal tumorigenesis

Gastrointestinal (GI) cancers are due to over time accumulation of genetic and epigenetic alterations resulting from complex interplay between host, bacterial and environmental factors. Several bacteria have been associated with GI cancers development. Our hypothesis is that GI tumorigenesis likely involves synergistic or sequential impacts of several pathobionts. Based on molecular tracks establishing links between bacteria and host pathways, we aim to understand how several pathobionts co-in...

#19304 : Adaptation to the gut environment

Archaea and Bacteria have adapted multiple times independently to the gut environment, but the general mechanisms of adaptation to this environment are not very well know or it as been studied on very specific models. This project is focused on the multiple adaptations of Archaea to the gut environment, with a comparison to selected lineages of Bacteria....

#19297 : CHIP-seq identification of IRF8 binding site

We are in the process of publishing a paper showing that IRF8, a transcription factor, regulates MS4A1 expression. Indeed, we showed IRF8 was necessary for MS4A1 expression by knocking-out the gene. A reviewer is asking us to directly assess IRF8 binding on MS4A1 gene using already published CHIP-seq data (PMID:31000603)....

#19291 : SatelliteFinder

Bacteriophage-bacteria interactions are key drivers of microbial populations. They are affected by phage satellites, which may facilitate, hinder or even block phage reproduction. These elements have been known for decades and shown to carry numerous defense systems, antibiotic resistance genes, and virulence factors. Yet, only recently it has become apparent that they are very diverse and numerous. Further understanding of their diversity and distribution has been hampered by the lack of a comp...

#19290 : Transcriptomic comparisons of African trypanosome infections in mouse skin and blood

African trypanosomes are flagellated protist parasites transmitted to mammals by the infectious bite of the tsetse fly. They are responsible for sleeping sickness in humans and nagana in cattle. Trypanosomes first proliferate freely in the blood, and then, about six hours after being inoculated, leave the bloodstream to invade various organs, including the skin, which is an anatomic reservoir for the parasites. Few details are known on the metabolic aspects of the different parasite stages in th...

#19289 : OLFACTORY DYSFUNCTION, NEUROINFLAMMATION AND NEUROINVASION IN POST-ACUTE COVID-19 SYNDROME

It is increasingly clear that SARS-CoV-2 infection does not only affect the airways, but also the central nervous system (CNS) by interfering with neurons, glial cells, and the immune response in the brain, sometimes leading to long-lasting neurological signs, including anosmia and anxio-depressive symptoms. These and other persistent symptoms constitute a new entity that is currently called Long-COVID or Post-Acute COVID-19 Syndrome (PACS), however, it still lacks definitive diagnostic criteria...

#19284 : Deciphering the role of viral transmission on the establishment of persistent infections

Several molecular pathways are known to play pivotal roles in Drosophila antiviral defense. The main parameters used to assess this response are fly survival and viral titers, which are both helpful to describe pathogenesis and virulence. However, little is known about the processes that prevent infection and if the known antiviral pathways are involved. Moreover, studies of the insect antiviral response are based on the administration of large doses of pathogens that barely simulate the physiol...

#19282 : High content screening of mitochondrial morphology defects in mitochondrial genetic diseases: discovery of new therapeutic compounds

Mitochondria are double-membrane bound organelles that act as metabolic hubs and signaling platforms, involved in an array of essential cellular processes that include the production of ATP by oxidative phosphorylation (OXPHOS), the generation and control of reactive oxygen species (ROS), metabolites biosynthesis, calcium homeostasis, inflammation, and programmed cell death. Mutations in mitochondrial genes cause a pleiotropic spectrum of clinical disorders whose underlying genetic, morphologica...

#19277 : Gitlab implementation and NMR data processing automatisation

The goal of this project is to centralize and automatize programming tasks inside the Biological NMR Platform. This can be done by implementing dedicated software such as Gitlab, snakemake/nextflow, and docker/singularity containers and training group members to use these tools efficiently....

#19259 : Clinical Metagenomics Analytical Flow

Clinical Metagenomics Analytical Flow...

#19257 : Neonatal acquisition of ESBL-PE in the community of a Low-Income Country

Severe bacterial infections are a leading cause of neonatal deaths, with low income countries (LICs) bearing the highest burden. In LICs, neonatal bacterial infections are mainly caused by Enterobacteriaceae. One important driver of unfavorable outcome in infections caused by these bacteria is multidrug resistance. Of particular concern, extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) are resistant to most penicillins and especially cephalosporins (3rd-4th generation). ...

#19255 : Genomic study of the Pseudoalteromonas genus

Based on the analysis of two bacterial strains isolated from the sea cucumber Holothuria forskali, we are describing a novel species in the genus Pseudoalteromonas. Vibrionaceae and Pseudoalteromadaceae represent the only two families from the gamma-proteobacteria class with multipartite genomes. Whereas the Vibrionaceae genome is well studied, the information on Pseudoalteromadaceae is scarce. In addition, the taxonomy of the genus Pseudoalteromonas needs to be greatly clarified....

#19239 : Human nasopharyngeal virome variation in healthy and disease individuals.

The Milieu Intérieur program aims to understand the genetic and environmental determinants of normal healthy immune responses. One component of this program involves analysis of the nasopharyngeal mucosal immune variation. At upper respiratory tract level, nasal-associated lymphoid tissue is strategically located to potential respiratory pathogens; in this context, B cell activation induces specific secretory IgA while T cells/ILCs produce cytokines. One factor that has been poorly studied and...

#19238 : Virulence and natural anti-sense RNA in Entamoeba histolytica, the agent of human amoebiasis

Several evolutionary processes influence microbes virulence, a process ending with damage impacting host survival. Parasites are favored to exploit their hosts prudently to prolong infection in general overcoming the host immune response and avoid killing the host. Parasites also need to use some host resources to reproduce and transmit infections to new hosts. We are interested in parasites affecting humans as Entamoeba histolytica, which is a protozoan parasite and an amitochondriate pathogeni...

#19226 : Kinase involvement in antifungal resistance in C. glabrata

A phenotypic study of antifungal tolerance have been performed with a collection of 100 mutant strains of C. glabrata and a statistical analysis of these data should be conducted....

#19224 : Transcriptional analysis of niche cells in the context of tumour progression in the Drosophila brain

We are interested in the behaviour of healthy cells in the context of tumour growth in the Drosophila brain We want to know the genes changing in healthy cells response to the tumour....

#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...

#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...

#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....

#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....

#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...

#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