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RegulatioNFkB

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Deciphering transcriptional regulation of NF kB target genes using integrative o...

Deciphering transcriptional regulation of NF kB target genes using integrative omics approaches 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 a... ver más

30/06/2021

STICHTING RADBOUD...

188K€

Presupuesto del proyecto: 188K€

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STICHTING RADBOUD UNIVERSITEIT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-06-30

MSCA-IF-2018: Individual Fellowships Objective:The goal of the Individual Fellowships is to enhance the creative and innovative potential...

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2 Participantes

STICHTING RADBOUD UNIVERSITE...

187.57K€ | Lider

VITAE CAPS

570.04K€ | Participante

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Duración del proyecto: 26 meses Fecha Inicio: 2019-04-17
Fecha Fin: 2021-06-30

Líder del proyecto

STICHTING RADBOUD UNIVERSITEIT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 188K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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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