IDPro · Intrinsically disordered proteins in health and disease: mechanisms, molecular context and opportunities for drug discovery

Proteins dictate virtually all cellular processes. To do so, precise 3D-structures that fit to their binding partners are exploited. However, up to 40% of the human proteome exist in disordered, dynamic ensembles of states mandatory for function. These so-called intrinsically disordered protein and regions (IDPs) play crucial roles in most aspects of life. They mediate tens of thousands of protein-protein interactions involved in cell signaling, scaffolding, transcription, membrane-less organelles and more. While the pivotal role of IDPs in biology is recognized, most of their functions remains unexplored. The time is now ripe for the next frontier, decomposing protein-protein interactions involving IDPs on a large scale. Importantly, IDPs are emerging drug targets for treating complex diseases: cancer, neurodegenerative disorders, metabolic syndromes and viral diseases, afflicting an ageing European population. The evolving field demands a new generation of experts to take the lead in developing different types of drugs targeting IDP interactions. This MSCA DN project aims to educate ten doctoral students within this evolving field by tackling outstanding questions. In particular, we will delineate the role of context in interactions involving IDPs, including flanking regions, folded domains, disease-related mutations, and aberrant cellular signaling and also design peptide-based ligands based on disordered regions that can potentially be further developed into drugs or molecular probes. A team of 14 established scientists from seven academic institutes and five companies, with excellent experience in supervision and cutting edge knowledge on IDPs and experimental and computational techniques will form IDPro. IDPro constitutes an exceptional network where the PhD students can mature and obtain scientific excellence in academic as well as non-academic settings. IDPro will strengthen the future academic and biotech labor force of the European union.