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RegulatioNFkB SIGNED

Deciphering transcriptional regulation of NF-kB target genes using integrative omics approaches

Total Cost €

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EC-Contrib. €

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Partnership

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Project "RegulatioNFkB" data sheet

The following table provides information about the project.

Coordinator
STICHTING KATHOLIEKE UNIVERSITEIT 

Organization address
address: GEERT GROOTEPLEIN NOORD 9
city: NIJMEGEN
postcode: 6525 EZ
website: www.radboudumc.nl

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 Netherlands [NL]
 Total cost 187˙572 €
 EC max contribution 187˙572 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-RI
 Starting year 2019
 Duration (year-month-day) from 2019-07-01   to  2021-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    STICHTING KATHOLIEKE UNIVERSITEIT NL (NIJMEGEN) coordinator 187˙572.00

Map

 Project objective

NF-kB is a family of transcription factors that regulate expression of genes that are involved in various cellular processes such as apoptosis, proliferation and differentiation. The NF-kB pathway is implicated in the initiation and progression of cancer and cancer cell drug resistance. Unfortunately, global NF-kB inhibition is harmful to the immune system; therefore, inhibition of a subset of NF-kB target genes that are linked to malignant transformation would be more appropriate. Different NF-kB target genes display distinct transcription activation kinetics, indicating that the molecular mechanisms driving expression of NF-kB target genes are strikingly diverse. Thus, it is highly interesting to study the factors that are involved in transcriptional activation of individual NF-kB responsive genes, both from a fundamental and clinical perspective. Here, we will develop two innovative strategies based on CRISPR/Cas9 based genome targeting combined with mass spectrometry-based technology to isolate single NF-kB target gene promoters upon NF-kB pathway activation and identify their constituents. We will also apply a complementary approach, ATAC-sequencing, to identify transcription factors that are involved in activation of NF-kB responsive genes. Moreover, we will study the underlying mechanisms and characterize the function of proteins that interact with NF-kB responsive promoters. Finally, the described mechanisms discovered in cancer cell lines will be verified and validated in small intestinal organoids, a non-transformed cell model for homeostasis in the intestinal epithelium. This ambitious and multidisciplinary project will greatly benefit from my expert knowledge regarding the NF-kB pathway combined with the expertise of the host laboratory in mass spectrometry and genomics. The project is expected to have a major impact in the research area of gene expression regulation in general and molecular cancer research focusing on the NF-kB pathway in particular.

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The information about "REGULATIONFKB" are provided by the European Opendata Portal: CORDIS opendata.

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