Schizophrenia (SZ) is a severe mental disorder affecting more than 0.7% of the adult population. One of the most disabling and emotionally devastating illnesses known to man, SZ is also associated with considerable socioeconomic burden. In general, the chronic nature and the high degree of patient disability make SZ the fourth leading cause of disease burden across the globe with the management costs making up ~3% of the total healthcare budget in the Western countries. The situation is even direr in some regions, including northern Sweden and Finland, where relative prevalence of SZ exceeds two to three times corresponding national or regional averages. Poorly understood aetiology and limited diagnostic arsenal make it difficult to detect and treat SZ in a timely and efficient manner. This underscores a critical need for better understanding of the mechanisms underlying SZ and development of new diagnostic possibilities allowing its early detection, ideally prior to the onset of psychosis. The SZ_TEST will address these challenges by coordinating efforts with complementary areas of expertise in genetics, epigenetics, neurodevelopment, molecular psychiatry, clinical immunology and biotech R&D. The overarching hypothesis underlying our work is that genetic vulnerabilities, neurodevelopmental defects, exposure to pathogens, immune system status and specific lifestyle choices may compound the risk of SZ and that a systematic multivariate analysis of these factors should result in substantially improved diagnostic tools. SZ_TEST will work towards the development of molecular diagnostics tools for early detection of SZ, by using relevant cohorts of human subjects, unique animal and cell models, and combining unbiased high-throughput omic screens with knowledge-based candidate marker analyses. SZ_TEST training network is expected to have a major impact on improving the quality of life and reducing the health care costs in Europe and worldwide.

Due to the chronic relapsing nature of mental disorders and increased life expectancy, the societal burden of these non-communicable diseases will increase even further. Treatments for mental disorders are available, but their effect is limited due to patients’ (genetic) heterogeneity, low treatment compliance and frequent side effects. Only one-third of the patients respond to treatment. Today, medication selection in psychiatry relies on a trial-and-error approach based mainly on physicians’ experience. Pharmacogenetic testing enables assessing person-specific genetic factors that predict clinical response and side effects. Recent studies show that genotyping of drug-metabolizing enzymes can increase the effectiveness of treatment, which could benefit millions of patients. PSY-PGx is the first initiative to propose a large-scale non-industry sponsored clinical study that demonstrates the clinical benefits and potential of implementing pharmacogenetics for psychiatric patients in existing medical settings. To this end 1) available biobank data (www.biobankki.fi, www.ukbiobank.ac.uk), with the aid of AI, will be searched for pharmacogenetics that influence medication response. This information is used to 2) perform a clinical trial that will be the first large international, multicenter clinical trial on using pharmacogenetic-based treatment personalization in real-life psychiatric care for depressed, anxiety or psychotic disorder patients. All data is combined with AI to set-up an algorithm for personalizing medication prescription for psychiatric patients that reduces side effects and increases effectiveness of pharmacotherapy. PSY-PGx will thus deliver a new model of care for sustainable healthcare systems and reduce the suffering of psychiatric patients.

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.

PDZnet will create an innovative European PhD training network focusing on unraveling PDZ domain-mediated signaling networks. The emphasis will be on signaling nodes essential for the development of cancer and diseases of the nervous system, conditions that affect millions of Europeans and are major societal challenges. PDZ domains are protein and lipid recognizing modules that play a central role in trafficking and organizing diverse cell signaling assemblies, thereby allowing information to be transmitted from receptors, ion channels and transporters in the cell membrane. PDZ domain mediated interactions are emerging as conceptually novel and promising drug targets, with exciting opportunities for the development of novel therapies, especially within cancer and brain diseases. We will establish a European multidisciplinary platform integrating a plethora of complementary life science disciplines that range from chemical development of inhibitors to studies in live animals. The network encompasses 8 academic and 2 industrial beneficiaries as well as one industrial and one academic partner, which are all committed to promote frontline research, innovation and educational activities within the study of PDZ domain-mediated signal transduction pathways related to brain diseases and cancer. This interdisciplinary network will establish an outstanding training opportunity for Early Stage Researchers, who will be integrated in projects unraveling intracellular PDZ domain interactomes to provide pertinent information for discovering drug-related interactions. In a comprehensive and integrated training effort, involving a combination of scientific and transferable skills, the students will receive an interdisciplinary, intersectoral and innovative doctoral training from experienced industrial and academic leaders in well-reputed European Institutions.