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PlasmaCellControl SIGNED

Transcriptional control of plasma cell development and function

Total Cost €

EC-Contrib. €

Partnership

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PlasmaCellControl project word cloud

Explore the words cloud of the PlasmaCellControl project. It provides you a very rough idea of what is the project "PlasmaCellControl" about.

few rna libraries immunity cas9 secreting mutagenesis cells plasmablast discover quiescent xbp1 unknown experiments ranked mechanisms regulators systematically vitro lines mediated transcription mutant transcriptional expressing deletion screens regulated lived validation exception protection molecular plasma conditional functions cre aiolos extend genes seq implicated phenotypes fundamentally cell effector players consisting crispr potentially newly plasmablasts ikaros experiment infected irf4 proof upregulated loxp humoral rosa26 host interesting bhlha15 impaired sgrna protocols retrovirus proteins pooled pathogens optimized acute recapitulated retroviruses individual proliferating function showed followed vivo antibody hits chip performed blimp1 infection differentiation

Project "PlasmaCellControl" data sheet

The following table provides information about the project.

Coordinator	FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH Organization address address: CAMPUS-VIENNA-BIOCENTER 1 city: WIEN postcode: 1030 website: www.imp.ac.at contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Austria [AT]
Total cost	2˙500˙000 €
EC max contribution	2˙500˙000 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2016-ADG
Funding Scheme	ERC-ADG
Starting year	2018
Duration (year-month-day)	from 2018-01-01 to 2022-12-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH Organization address address: CAMPUS-VIENNA-BIOCENTER 1 city: WIEN postcode: 1030 website: www.imp.ac.at contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	AT (WIEN)	coordinator	2˙500˙000.00

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Project objective

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.