ERC Advanced Grant to chase the holy grail of ‘drugging the undruggable’

For Luc Brunsveld, the award of the ERC Advanced Grant is a key accolade that will help him achieve goals in terms of research and mentoring. “As a university, our first and foremost responsibility is to educate and train students to a high standard so that they can go on to roles as scientists in both industry and academia in the future,” says Brunsveld.

And according to Brunsveld, central to ensuring this training is the acquirement of external funding. “It is crucial that we as academic scientists in the natural sciences perform top-notch research with our students as this is a prerequisite to acquire further external research, such as this grant, to continue training students.”

Meet PPI-Glue

The prestigious ERC Advanced Grant will allow Brunsveld’s laboratory of Chemical Biology to pursue cutting-edge, high-risk research on the development of key innovations that could be used as integrated elements of drug development in the future.

And what are the elements in question? Well, they are previously unappraised classes of proteins. Brunsveld explains: “Existing drugs work through their interaction with a limited number of well-structured proteins in the body. However, many proteins are not well-structured. This puts strong limitations on drug development, especially for neurodegenerative diseases. So, to create the possibilities for new drug concepts, we need to enable drug discovery based on unstructured proteins.”

Enter project PPI-Glue – a project name with protein at its heart. Protein-Protein Interactions, or PPIs for short, are central to almost all biological processes in the body, while the glue part of the project name comes from the molecular glues that will be designed and explored to strengthen PPIs.

Brunsveld: “PPIs, in general, affect the activity of these unstructured, so-called intrinsically disordered proteins (IDPs), but at this moment it is very difficult to develop drugs that work via these PPIs. One of the main objectives of PPI-glue is to make IDPs druggable using their PPIs with a family of rigid proteins known as 14-3-3s (a systematic name that comes from a protein classification campaign from back in the 1960s, ed.).”

The high-risk part of the project, is to explore how these PPIs can be used to create new drugs suitable for the treatment of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s. “This part of the project is referred to as ‘drugging the undruggable’. It’s the highly explorative part of the project - the holy grail of PPI-glue,” notes Brunsveld.

Most exciting part

While the science certainly drives Brunsveld, this isn’t the most exciting part of the project. “For me, the most rewarding and exciting part is to offer talented master students, from TU/e and further afield, the opportunity to perform their PhD research with us in the laboratory of Chemical Biology. And it will also lead to hands-on training opportunities of bachelor and master students in lab-based chemical biology research via guidance by these PhD students. I can’t wait to get started on this project with the new research team.”

About the current ERC Advanced Grants

The European Research Council (ERC) has announced the awarding of 218 Advanced Grants to outstanding research leaders across Europe, as part of the Horizon Europe programme. Fourteen of these research leaders are based in the Netherlands. The grants - totalling €544 million - support cutting-edge research in a wide range of fields, from medicine and physics to social sciences and humanities.

This call for proposals attracted nearly 1,650 applications, which were reviewed by panels of renowned researchers. The overall success rate was 13.2%. Female researchers account for 23% of all applications, their highest participation rate in Advanced Grant calls up to now.

Established by the European Union in 2007, the ERC is Europe's leading funding organization for top-level pioneering research. It funds creative researchers of all nationalities and ages to carry out projects across Europe. The ERC offers four core grant schemes: Starting Grants, Consolidator Grants, Advanced Grants and Synergy Grants.