CORDIS
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Endothelial RNA Modifications in Vascular Homeostasis and Disease

Project information

Grant agreement ID: 759248

Status

Ongoing project

  • Start date

    1 June 2018

  • End date

    31 May 2023

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 499 250

  • EU contribution

    € 1 499 250

Hosted by:

UNIVERSITY OF NEWCASTLE UPON TYNE

United Kingdom

Objective

Endothelial cells cover the entire arterial and venous tree, and play a pivotal role in vascular and organ homeostasis. In general, cardiovascular risk factors induce endothelial cell activation towards a pro-inflammatory phenotype leading to atherosclerosis, a major cause of mortality in the Western world. Understanding the mechanisms that orchestrate endothelial cell functions and response to environmental stimuli is essential for the discovery and development of novel biomarkers and therapeutic strategies in vascular disease.
RNA base modifications increase the RNA alphabet from the 4 canonical nucleotides to more than 140. Adenosine methylation at the N6 position (m6A) is the most prevalent RNA modification in eukaryotic mRNA and is catalyzed by a multiprotein methyltransferase complex. Accumulating recent evidence suggests that m6A RNA methylation is a critical posttranscriptional regulator of RNA metabolism. In preliminary unpublished work we have identified methylated RNA targets, which may critically regulate endothelial cell functions. Since the impact of m6A RNA methylation on vascular function is completely unknown, MODVASC aims to explore the role of m6A RNA methylation in vascular growth, homeostasis and disease. By m6A-RNA immunoprecipitation followed by RNA-sequencing we will identify the transcriptome-wide m6A RNA methylation in endothelial cells under basal and stress conditions. With the help of advanced molecular biology and biochemical methods, we will describe in single nucleotide level the impact of m6A RNA methylation on mRNA fate and RNA-protein interactions and define its functional consequences in endothelial cell functions. In vivo studies will consolidate the impact of endothelial RNA methylation on vascular growth and homeostasis as well as its contribution to atherosclerosis. Finally, MODVASC will evaluate the clinical relevance of our findings in patients with cardiovascular disease.

Host institution

UNIVERSITY OF NEWCASTLE UPON TYNE

Address

Kings Gate
Ne1 7ru Newcastle Upon Tyne

United Kingdom

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 499 250

Beneficiaries (1)

UNIVERSITY OF NEWCASTLE UPON TYNE

United Kingdom

EU Contribution

€ 1 499 250

Project information

Grant agreement ID: 759248

Status

Ongoing project

  • Start date

    1 June 2018

  • End date

    31 May 2023

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 499 250

  • EU contribution

    € 1 499 250

Hosted by:

UNIVERSITY OF NEWCASTLE UPON TYNE

United Kingdom