ERC Advanced Grants for Ronald van Rij and Nico Sommerdijk Millions for research on virus transmission in mosquitoes and aortic valve calcification

The European Research Council (ERC) funds research by Ronald van Rij and Nico Sommerdijk, both professors at Radboud university medical center. Van Rij will investigate how mosquitoes defend themselves against viruses and use that knowledge to develop new strategies to block virus transmission. Sommerdijk is developing a heart valve-on-a-chip to study the calcification of the aortic valve. He will visualize this process dynamically with the first microscope worldwide that can display this at the nanoscale. This is Sommerdijk's second consecutive ERC Advanced Grant.

Ronald van Rij: How mosquitoes defend themselves against viruses 

The mosquito Aedes aegypti can transmit harmful viruses to humans, causing for instance dengue and yellow fever. Besides the transmission of viruses from mosquito to human, some viruses can invade the ovaries and eggs of female mosquitoes. In this way they are transmitted from mother to offspring and spread within the mosquito population. To do so, viruses must overcome the mosquito's immune response, resulting in an intriguing conflict between virus and mosquito that has not yet been studied. 

An important defense mechanism of mosquitoes against viruses depends on small RNA molecules. Van Rij and his team will map this small RNA-based defense, for example, by disabling this mechanism in mosquitoes and studying the course of infection. The researchers will also investigate whether viruses sabotage the defense to be transmitted more efficiently. Furthermore, they will explore whether it is possible to adjust the mosquito's defense to prevent virus transmission to humans. 

Ronald van Rij: 'In this project, we will use new genetic techniques to study how the defense against pathogens works in an important mosquito species. The project generates fundamental insights into virus-host conflicts and may offer new approaches to reduce virus transmission by mosquitoes.' 

Nico Sommerdijk: Dynamically visualizing aortic valve calcification 

Calcification of the aortic valve leads to severe heart defects. In this condition, changes appear in the structure and composition of the tissue in the valve outside the cells, the so-called extracellular matrix. Normally, this matrix provides strength and structure to tissues. It is still unknown why this structure changes, mainly because good methods to investigate this process are lacking. Consequently, there is currently no drug-based therapy available, and valve replacement is the only available treatment. 

Sommerdijk and his team will develop advanced electron microscopy methods to investigate how the disease changes the affected tissue, how this leads to calcification, and how the calcification develops. Sommerdijk will create a model of human aortic tissue on a chip. In this model, chemical and mechanical signals can be applied that precisely mimic how calcification occurs. The new transmission electron microscope at Radboudumc plays a crucial role in visualizing the calcification processes. This is the first electron microscope in the world specifically built to make biological processes visible at the nanoscale in a fluid. This project will thus provide the first dynamic imaging of aortic valve calcification. 

Nico Sommerdijk: 'This project enables breakthroughs in understanding the molecular processes in the matrix during heart valve calcification. It paves the way for future drug-based treatments for aortic valve calcification and potentially other forms of pathological calcification.' 

More information

European Research Council – ERC Advanced Grants of 2.5 million euros each for:

• Project Ronald van Rij: PIWI-interacting RNAs at the interface of virus-host conflicts in Aedes aegypti mosquitoes (PIWIdefense) 
• Project Nico Sommerdijk: Real-time Multiscale Imaging of Pathological Calcification - Zooming in on Aortic Valve Calcification (REVALVE)

The researchers have been invited to start the grant agreement preparations.

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