Atherosclerosis, the most frequent cause of death in the western world, usually starts with a pro-inflammatory activation of arterial endothelial cells, a process that affects the structure and function of blood vessels and which may ultimately lead to acute myocardial infarction or stroke. It is still unclear so far how endothelial cells “sense” the environmental stimuli and how pro-inflammatory processes are controlled. With the help of an ERC Starting Grant of € 1.5 million awarded by the European Research Council (ERC), Professor Konstantinos Stellos now plans to examine the process at single-nucleotide level of RNA molecules.

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Increasing recent evidence suggests that RNA is not just a passive copy of the genetic code serving the production of proteins, the building blocks of cells, but it is a major regulator of the intracellular transport and stability of genetic information allowing or inhibiting its decoding to proteins. Even today, how RNA rapidly mediates cellular adaptation processes to environmental stimuli is not fully understood. For example, it is still far from clear whether chemical modifications to the RNA have an influence on gene expression, endothelial cell function and therefore on atherosclerosis.

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The research group led by Prof. Konstantinos Stellos has observed two particularly common chemical modifications in the RNA of endothelial cells that occur in atherosclerosis. He has recently published that adenosine-to-inosine RNA editing is a critical regulator of RNA metabolism in atherosclerotic heart disease (Nature Medicine 2016; 22(10):1140-1150). His intention now is to investigate another RNA modification in detail, namely the impact of RNA methylation on blood vessel function.

 

The researchers aim to increase our understanding on how RNA methylation affects gene expression, which proteins play a role in this context and what is the impact of RNA methylation on vascular inflammation and atherosclerosis. Their bench findings will be further “translated” into patients with coronary heart disease. They also hope to detect biomarkers, which reveal early signs of atherosclerosis in general population as well as to develop new therapeutic strategies for this common disease.

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With the ERC Starting Grant, the European Union funds every year outstanding early-career scientists enabling them to pursue groundbreaking ideas at an institution of their choice in Europe. The European Research Council, set up by the European Union in 2007, is the first European funding organisation for excellent frontier research. Every year, it selects and funds the very best, creative researchers of any nationality and age, to run projects based in Europe. The ERC has three core grant schemes: Starting Grants, Consolidator Grants and Advanced Grants. The grants are awarded under the 'excellent science' pillar of Horizon 2020, the EU's research and innovation programme. The ERC received 3,085 proposals in this call of which around 13% were funded. Prof. Konstantinos Stellos is among the very few physician scientists who have been awarded with the prestigious ERC Starting Grant.

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Further information can be found here.