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INSERM

Inserm
Country: France
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936 Projects, page 1 of 188
  • Funder: EC Project Code: 759120
    Overall Budget: 1,787,400 EURFunder Contribution: 1,787,400 EUR

    mRNA translation consists on translating the genetic code to proteins by the ribosome that is universally conserved in all cells. However, its structure presents significant differences between bacteria and eukaryotes. Partly because of these differences, the bacterial ribosome can be targeted specifically by a number of antibiotics without affecting the eukaryotic host cells. However, the conservation of the ribosome among eukaryotes complicates the search for specific drugs against eukaryotic pathogens such as certain protozoa like plasmodium and kinetoplastids. Our work along with other studies demonstrates the existence of significant structural differences between ribosomes of protozoa and mammals. Using Cryogenic electron microscopy, we endeavor to investigate such structural differences that are anticipated to affect some of the vital steps of mRNA translation, especially the initiation process, because of their position on the ribosome. 1. Thus we will focus on the structural differences in translation initiation between kinetoplastids and their mammalian hosts (i) by characterizing initiation complexes from several plasmodium and kinetoplastids species and compare them to their mammalian counterparts. (ii) We will also follow up on our previous works in solving the structures of various conventional, but also unconventional mammalian initiation complexes, in interaction with special mRNAs. 2. We will focus on the structure of protozoa-specific features characterized from elongating ribosomal complexes and (i) attempt to fish for regulators that they interact with from cell extracts. In addition, (ii) we will investigate the ribosomal structures from plasmodium at different stages of the parasite life cycle, as they vary according to the latter. Our results will significantly advance our understanding of protein synthesis regulation in protozoa and will represent a promising step in the search for more efficient treatments against these eukaryotic pathogens

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  • Funder: EC Project Code: 254747
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  • Funder: EC Project Code: 101001420
    Overall Budget: 1,541,620 EURFunder Contribution: 1,541,620 EUR

    Socioeconomic inequalities in children’s neurodevelopment and mental health are observed from early onwards and widen over time. Moreover, children whose parents are immigrant, particularly if they belong to ethnic minority groups, may be especially vulnerable. Yet there are important inter-individual differences in development, implying the possibility of resilience. My project will examine the consequences of multiple forms of socioeconomic adversity in children’s family and broader social environment with regard to their neurodevelopment and mental health, testing the role of social supports as sources of resilience. Specifically, I will rely upon longitudinal data collected from the ELFE child cohort study, a nationally representative sample of 18 321 children born in France in 2011 and followed-up to age 10.5 years, which will be linked with longitudinal administrative and geographical information characterizing neighbourhoods of children’s school and residence, as well as healthcare use data. Potential resilience factors will include familial (e.g. relations between the child and his/her mother and father, grandparents’ involvement) and contextual social supports (e.g. childcare prior to school entry, neighborhood social capital). Lifecourse patterns of adversity and resilience at each level of analysis will be identified using statistical methods developed for high-dimensional data and their influence on children’s development will be ascertained applying methods that strengthen causal inference (e.g. propensity scores). The results will help clarify 1) the ways in which lifecourse patterns of exposure to adversity in the family and children’s broader social environment can influence neurodevelopment and mental health, particularly among children of immigrants; 2) familial and collective factors that can help children overcome the odds and should be promoted.

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  • Funder: EC Project Code: 235934
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  • Funder: EC Project Code: 101088622
    Overall Budget: 2,475,810 EURFunder Contribution: 2,475,810 EUR

    Respiratory viruses can rapidly spread worldwide with a devastating impact, as dramatically highlighted by the COVID-19 pandemic. In addition to the pandemic threat posed by influenza A viruses (IAV) or coronaviruses, respiratory viruses, including IAV, influenza B virus (IBV), seasonal coronaviruses and respiratory syncytial virus (RSV), are the cause of yearly epidemics, with a huge impact on human health. The vast majority of in vitro studies has been performed with model cancer cell lines. However, they share limited features with the primary cells found within the human respiratory epithelium. Robust and relevant, ex vivo models of human primary airway epithelia, cultured at the air-liquid interface (ALI) have been developed over the years and nicely recapitulate the structure and composition of the in vivo respiratory epithelium. Nevertheless, in depth studies on the genes and the potent innate immune, interferon (IFN)-induced, defences regulating viral replication in such pertinent models are still lacking. The InVIRium project will address this knowledge gap by combining a newly acquired expertise in the generation and gene editing of human ALI airway epithelia, with a strong expertise in CRISPR screens and virology. The objectives of InVIRium will be to explore in depth the relationships between major human respiratory viruses, SARS-CoV-2, IAV, IBV and RSV, and their relevant, primary target cells. InVIRium will characterize the IFN-stimulated-genes responsible for the potent antiviral state, explore the mechanisms of SARS-CoV-2 escape from the IFN system and define the landscape of host genes regulating respiratory virus infection in this physiologically relevant ALI model. InVIRium will bring a change of paradigm in the way we study respiratory viruses, by implementing cutting-edge approaches in highly pertinent human models and will gather fundamental knowledge that is currently lacking on the interactions between viruses and their primary target cells.

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