May 27, 2021

ERC Grant at UKonstanz: Alarmones as drivers in cellular stress

Konstanz chemist Professor Andreas Marx has been awarded the prestigious Advanced Grant of the European Research Council (ERC) for the second time. His new project examines what are known as alarmones and their function in the post-translational modification of proteins in response to cellular stress. The work will help to better understand the role of this process in diseases such as cancer or degenerative disorders of the nervous system.

The genome contains all the inheritable information of a living organism. With its approximately 20,000 genes, which carry the instructions for protein production, the human genome has far fewer genes than that of a cauliflower. And yet the human body is much more complex in its development, structure and function than the vegetable. The solution to this riddle lies partly in the post-translational modification of proteins, which greatly increases the number of protein variants compared to the pure number of genes.

In his ERC-funded project with the title “Diadenosine Polyphosphate Alarmones as Drivers for Protein AMPylation”, Konstanz-based chemist Professor Andreas Marx and his research group will study a certain form of this subsequent modification of proteins, called AMPylation. In AMPylation, an adenosine monophosphate – in short AMP – attaches to the proteins through a process known as covalent bonding, causing the proteins’ properties to change. 

The project will especially shed light on the role that “alarmones” play in this process. “We’ve known for decades that alarmones are found in greatly increased concentrations in the cell during stress and there is reason to believe that they serve as signalling agents and regulate the cell’s stress response,” explains Marx. “To date, however, no one knows exactly how this happens. Our project will thus make a fundamental contribution to explaining these processes.” 

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