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EU-Förderung (187.572 €): Entschlüsselung der transkriptionellen Regulierung von NF-kB-Zielgenen unter Verwendung integrativer Omics-Ansätze Hor03.05.2019 EU-Rahmenprogramm für Forschung und Innovation "Horizont"
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Entschlüsselung der transkriptionellen Regulierung von NF-kB-Zielgenen unter Verwendung integrativer Omics-Ansätze
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.
Geförderte Unternehmen:
| Firmenname | Förderungssumme |
| STICHTING RADBOUD UNIVERSITEIT | 187.572 € |
Quelle: https://cordis.europa.eu/project/id/835908
Diese Bekanntmachung wurde von Englisch nach Deutsch übersetzt. Die Bekanntmachung bezieht sich auf einen vergangenen Zeitpunkt, und spiegelt nicht notwendigerweise den heutigen Stand wider. Der aktuelle Stand wird auf folgender Seite wiedergegeben: Stichting Radboud Universiteit, Nijmegen, Niederlande.
