Explore the words cloud of the PlasmaCellControl project. It provides you a very rough idea of what is the project "PlasmaCellControl" about.
The following table provides information about the project.
FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
|Coordinator Country||Austria [AT]|
|Total cost||2˙500˙000 €|
|EC max contribution||2˙500˙000 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2018-01-01 to 2022-12-31|
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|1||FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH||AT (WIEN)||coordinator||2˙500˙000.00|
Antibody-secreting cells consisting of short-lived proliferating plasmablasts and long-lived quiescent plasma cells are essential for the acute response to infection and long-term protection of the host against pathogens. Only a few regulators (Blimp1, IRF4, XBP1, Aiolos, Ikaros and E-proteins) have been implicated in the transcriptional control of antibody-secreting cells, and their target genes, with the exception of Blimp1 and E-proteins, are still unknown. This proposal aims to systematically identify key players in the development and function of antibody-secreting cells by using the CRISPR/Cas9 and Cre/loxP methods. For this, we improved existing protocols to extend the duration of in vitro plasmablast differentiation and showed that Rosa26(Cas9/) B cells infected with Blimp1 or Xbp1 sgRNA-expressing retroviruses recapitulated the Blimp1 and Xbp1 mutant phenotypes in this proof-of-principle experiment. Moreover, Cre retrovirus-mediated deletion of Irf4, Ikaros and Aiolos strongly impaired plasmablast differentiation in this optimized system. To discover new regulators of plasma cell differentiation, CRISPR/Cas9-based screens will be performed with pooled sgRNA libraries targeting all known upregulated genes in plasmablasts and plasma cells, followed by individual validation of the best hits. Selected top-ranked genes will be analyzed in vivo by conditional mutagenesis with newly generated, plasma cell-specific Cre lines. Regulated target genes of IRF4, Ikaros, Aiolos, XBP1 and the XBP1-regulated transcription factor Bhlha15 will be identified in plasmablasts by ChIP- and RNA-seq analyses. Target genes with potentially interesting functions will be further characterized by CRISPR/Cas9- or Cre/loxP-mediated mutagenesis. These experiments will provide fundamentally new insight into the molecular mechanisms controlling the development and function of antibody-secreting cells, which are the essential effector cells of humoral immunity.
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The information about "PLASMACELLCONTROL" are provided by the European Opendata Portal: CORDIS opendata.