The Network

The development of RIC and various other methods that select RBPs crosslinked to RNA has been essential for expanding the compendium of RBPs. These methodologies have led to the identification of several candidate RBPs that will be examined in depth in this proposal, including metabolic enzymes in cancer cells, or p62/SQSTM1 after SARS-CoV-2 infection from the Castello group, or in T cells from the Wolkers group.

Although RICs provide a powerful tool to detect biochemical RNA binding in cells, only functional follow-up experiments can establish the biological relevance of newly detected RBPs. Candidate RBPs that will be selected for further characterization as drug targets should have a meaningful impact on key biological processes. In this WP2, we will disrupt RBP-RNA interactions in disease relevant cellular and in vivo models and examine how this affects pathophysiological processes. On the other hand, once potential drug targets are identified (WP4), their effectiveness in disease models has also to be demonstrated.

A key step in characterizing the molecular and cellular function of novel RBPs is to identify their RNA targets, and at which level they are regulated by RBPs (splicing, stability, translation), or whether riboregulation is in place. These are the critical steps towards a mechanistic understanding of the disease.

In the past, RBPs were considered largely ‘undruggable’ because of the lack of enzymatic pockets typically targeted by small molecules, the high structural similarity between individual members of RBD families and the significant fraction of unstructured regions present in these proteins. Here, we will pursue various strategies for targeting RBPs, including using the high-capacity infrastructures owned by INNOPHARMA (part of KAETOR, Associate Partner SME), one of the seven high-capacity nodes of the European Research Infrastructure Consortium (ERIC) EU-OPENSCREEN.

The WP will be undersupervision of the Training/Doctoralstudies Committee, and involving all network partners and DCs. The main objectives will be the establishment of DC Personal and Research Career Plan (PRCP), the organisation of local training activities for the DCs, the organization of network-wide training activities, including three workshops (M8, M18 & M30), two RBP-ReguNet international meetings (M24 & M40), and five courses of Transferable skills (M8, M18 & M30), and the secondments in which the DCs will circulate among the network.

This WP will encompass the elaboration of the Dissemination, the Public Engagement, the Gender Dimension Implementation, and the Data Management plans. The organisation of scientific events will be also one of the tasks if WP6.

The main objectives of WP7 will be to organize a well-defined time-schedule of research and DC training, ensuring the achievement of planned objectives, risk management strategies and problem-solving. To ensure full synergy and integration between consortium participants.