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Role of SUMO in interferon pathways : Identification of SUMOylated proteins in response to interferon – SUMO and IFN
Interferons (IFNs) are a family of cytokines that exhibit diverse biological activities. Identified and named for their antiviral properties, IFNs have also immunomodulatory, antiproliferative and apoptotic activities. IFNs are successfully used in therapy to treat viral infections, cancer or multip
Pathophysiological implications of IgH locus accessibility to chromatin remodelling and to AID activity. – IgH-AID-Access
B lymphocytes are unique in that they diversify their antigen receptors through somatic hypermutation (SHM) and class switch recombination (CSR). These transcription-dependent reactions are initiated by DNA damage inflicted by the Activation Induced Cytidine Deaminase (AID) enzyme. Restricting acces
Mechanism of extended self renewal in mature differentiated macrophages – ReNEW
Our observation that MafB/c-MafB deficient macrophages show extended self-renwal, without malignant transformation, loss of differentiated function or stem cell intermediates represents a novel concept as self-renewal normally is a defining characteristic of stem cells. We want to decipher the un
Coordinating signaling, cytoskeleton and intracellular traffic to control major leukocyte effector functions – LEUKOSITRACY
Even if their functions are very different, some immune cells utilize very similar intracellular mechanisms. The two partners in this project previously showed that intracellular signaling, cytoskeleton and targeted vesicle traffic play key roles in T cell and macrophage functions. The goal of this
Integrative Mobile genetics Elements hijacking the bacterial Chromosome dimer resolution machinery: contribution to the emergence of new pathogenic strains. – IMEX
The aim of this project is to decipher the mechanisms that permit the activity of the Xer machinery when it is hi-jacked by mobile elements. Revues à comité de lectures Das B, Martinez E, Midonet C, & Barre FX (2012) Integrative mobile elements exploiting Xer recombination. Trends Microbiol 21(1):2
Structure and evolution of membrane fusion protein complexes of the alphaviruses – StrucEvolAlpha
Fusion is crucial to many biological processes, vesicular trafficking, fertilization... Fusion between cellular and viral membranes, first step of a viral infection is a model of choice to study the fusion mechanism and the evolution of fusogenic proteins.Our project aims to better undertstand this
Iron Sulfur cluster biogenesis under stress conditions – FeStreS
Iron-sulfur (Fe-S) clusters are inorganic cofactors, ranking among the oldest catalysts in the evolution of life and are found in all kingdoms of life as parts of a large number of proteins involved in most cellular processes, such as DNA replication, repair, gene expression, metabolism, respiration
Characterization of Plasmodium species in wild chimpanzees, gorillas, bonobos and humans in rural forest areas in order to evaluate the presence of a primate reservoir for human malaria in Central Africa. – PRI-MAL
It is now well established that wild African apes are infected with at least 9 different Plasmodium species, with 1 being at the origin of the P. falciparum pandemic. The overall goal of this study is to determine whether the recently identified Plasmodium species of the Laverania subgenus and othe
Heterospecific non self recognition in filamentous fungi : from receptors to the cellular response – Mykimun
Immune responses in plants and animals rely on comparable immune receptors of the NB-LRR type that are believed to result from a convergent evolution. This type of receptors are absent from fungal genomes, the third branch of the eukaryote kingdom. We set up to identify fungal immune receptors and t
The Ikaros family proteins: molecular targets and downstream events in lymphocyte development – Ikaros-in-Lymphocytes
Proteins of the Ikaros family regulate gene expression, and bind to specific sequences on the chromosomes. Several members of this family have been involved in lymphocyte development (Ikaros, Aiolos, Helios, Eos), but their function is not well understood. We aim to better understand these functions
New mechanisms involved in the exceptional radioresistance of the bacterium Deinococcus radiodurans – Radioresistance
Many different mechanisms contribute to D. radiodurans radiation resistance: efficient DNA double strand break repair, protein protection against oxidation, compaction of DNA inside the cell, induction of specific genes in response to radiation exposure, but several factors still remain controversia
Signalling to Epigenetics: Remodelling of the host cell epigenome by Theileria during parasite-induced leukocyte transformation – S2E_Thei
Theileria, a member of the phylum Apicomplexa that includes the deadly pathogens Plasmodium and Toxoplasma, is the only eukaryote known to transform its host cell and constitutes a unique model system to explore parasite-host interactions. Our ambitious project brings together parasitologists, cell
Deciphering the molecular mechanisms of PI3P-mediated vesicular transport to the apicoplast in apicomplexan parasites – APICO-PIP
Despite prevention campaigns, availability of medicines and insecticides, malaria is still a threat for the world population. The apicoplast is absent from the host organism. Therefore this organelle represents a priority target for drug design. Our fundamental project partly relies on Toxoplasma as
Role of the Neisseria meningitidis PTS component HPr in the correlation between carbon metabolism and virulence – MeniViruCarb
Neisseria meningitidis is an exclusively human pathogen, which represents a major threat to health. It is commensal of the nasopharynx with 10 to 15% of the population in Europe being asymptotic carriers. Upon specific signals, which have not yet been identified, N. menigitidis crosses the epitheli
Coevolution of Caenorhabditis nematodes and viral pathogens – CAENOVIRUS
The present project proposes to build on these preliminary results and undertake the following studies about C. elegans anti-viral immunity and viral host specificity: Task 1: Characterization of the infection of the model organism C. elegans by the newly discovered Orsay virus and development of i
Regulation of the antibacterial immune response in drosophila respiratory and intestinal epithelia – RegImDep
Notre tube digestif contient plus de bactéries que notre corps contient de cellules. Ces bactéries qui persistent en nous ont des répercutions essentielles sur de nombreuses fonctions de notre organisme. Cet ensemble bactérien est aujourd’hui considéré comme un organe à part entière. Pour connaître
Host and parasite pathways controlling exogenous MHC I antigen presentation during Toxoplasma gondii infection – CROSSTOX
T. gondii infection can have dramatic consequences in immunocompromised individuals, as well as in fetuses. Furthermore, T. gondii represents an interesting model to study other intracellular parasites, such as the one responsible for malaria. These pathogens have developped strategies to survive
Role of SigmaS in bacterial fitness and adaptation to the environment – SIGMADAPT
SigmaS remodeles the physiology of Salmonella to favor stress survival and virulence while limiting capacity for growth. This project aims at identifying targets and major players in this strategy. We will assess: 1) how SigmaS activity is regulated, 2) whether and how the negative effects of SigmaS
Research of emergent pathogens in Africa – MALEMAF
The techniques of diagnosis in bacteriology in the time of care are quickly changing with the installation of fast molecular detection on targeted micro-organisms. It is possible that in poor and emergent countries, the strategies of culture of the 20th century, which are specialized and heavy, woul
Identification of key cellular pathways and genes involved in the pathogenicity and resistance to Rift Valley Fever virus. – GenRift
The Rift Valley fever virus is transmitted by mosquitoes. It is responsible for a severe zoonosis both in terms of morbidity and mortality in humans and livestock. The virus was first identified in 1931 in the greater Rift Valley of Kenya. The Rift Valley fever virus has already demonstrated a real
Cellular and structural bases of MHC/peptide complex antigenicity in humans – pMHCantigenicity
- - - - The aim of our project is to determine the overall characteristics of naive T cell repertoires directed against various viral or tumoral antigens in humans as well as parameters influencing these repertoires both qualitatively and quantitatively. An in depth understanding of these mechanisms
Genetic dissection of chronic muco-cutaneous candidiasis in humans – GENCMCD
To identify the genes responsible for an increased susceptibility to chronic mucocutaneous candidiasis, we are combining a specific recruitment of patients presenting this disease without any other clinical disorder to powerful and innovative genetic techniques. These studies should lead to the desc
Rac1 E3 ubiquitin-ligase in bacterial invasion and inflammation – RacLig-HPI
The aim of our studies is to determine the implication of the Rac1/HACE1 signaling axis in cell homeostasis and implication upon dysregulation in major human diseases, comprising cancer, inflammatory disorders and infection. Hace1 is a negative regulator of the GTP-bound active form of Rac1. We have
Epigenetic reprogramming by the pathogenic bacterium Listeria monocytogenes – EPILIS
It is a priority to characterize, during infection, the molecules that are important for regulating specific genes and to identify which factors alter and are the cause of observed pathologies. Bacterial pathogens can interfere with host nuclear proteins and modify the expression of genes important
Elucidation of the metabolism of undecaprenyl phosphate, a key lipid for bacterial cell wall polymers biosynthesis – BACTOPRENYL
The aim of the present project is to increase our fundamental knowledge on the biosynthesis and recycling of the carrier lipid undecaprenyl-phosphate which plays a central and essential role in the biogenesis of the bacterial cell wall. The project includes the identification of the genes and enzyme
Interaction PGL /lectins and modulation of the host immune response by mycobacterial pathogens – PGLECT
Tuberculosis, leprosy and Buruli ulcer consitute challenges to global public health, causing death, suffering, economic losses and poverty. We must improve our basic knowledge of the biology of bacteria responsible of these diseases and of the factors important for the pathogenesis and their mechani
Pro-inflammatory immunity and intestinal homeostasis – INFHOM
Inflammatory bowel disease, including Crohn's disease and colitis, affect more than 1% of the western population. Current treatments include partial immunosuppression, antibiotics and surgery. We aim at understanding how rupture of the intestinal equilibrium leads to inflammatory disease, and at dev
HTLV-1-associated cellular posttranscriptional deregulation – EPIVIR
The aim of this project is to produce a qualitative and quantitative explanation of some mechanisms by which the human lymphotropic retrovirus HTLV-1 persists in the host. Team 1 is involved in HTLV-1 research and has previously demonstrated that the virus persists in its host in a cell-associated m