Recent pandemics showed Europe how serious health threats can be to society. Proactive approaches are needed to ensure that medical countermeasures are available during pandemics. PROACT EU-Response’s overarching objective is to prepare Europe for future pandemics by strengthening upon existing networks of experts and civil society focused on clinical therapeutic platform trials within hospital inpatient settings across Europe. In case of an outbreak, this network will provide capacity to pivot rapidly to implement large, multi-country platform trials studying therapeutics and diagnostic-tool performance. Underpinned by strong community involvement and further strengthened by the inclusion of social and implementation scientists, PROACT EU-Response centres on six objectives: expand a solid network of clinical centres across Europe that will implement a clinical trial assessing a syndromic approach for respiratory viral infections; strengthen a laboratory network to identify pathogens and biomarkers of disease monitoring for routine surveillance; support a network of methodologists and trialists who will ensure the trials’ logistical and methodological aspects; initiate a network of professionals to work on preparedness tools to ensure a smooth pivot from inter-pandemic to the pandemic period in case of an outbreak; build a network of social science researchers who will provide nuanced understanding of the social contexts; and establish a community group to work on activities that will empower patients and citizens in Europe regarding their own health and educate them about science and health issues. By bringing together scientists, social science researchers, and civil society members, PROACT EU-Response will benefit the entire European population and beyond through decreased mortality and morbidity associated with emerging diseases, lower societal economic costs of morbidity, strengthened research and innovation expertise, human capacities, and know-how for combatting communicable diseases.

The lack of realistic in vitro organ models that can faithfully represent in vivo physiological processes is a major obstacle affecting the biological and medical sciences. The current gold standard is animal experiments, but it is increasingly clear that these models mostly fail to recapitulate the human physiology. Moreover, animal experiments are controversial, and it is a common goal in the scientific community to minimize the use of animals to a strictly necessary minimum. The emergence of stem cell engineered organ models called organoids represents the only viable alternative to animal research. However, current organoid technology is yet to produce the larger physiologically relevant organmodels that the medical sciences really need. Specifically, current organoids are too small, not vascularized and lack the 3-dimensional organization found in vivo. In this interdisciplinary project we aim to challenge all these limitations by using the recently developed gastruloid technology guided by cutting edge bioengineering and artificial intelligence. Gastruloids are formed by initiating the very early developmental processes and develops along a highly coordinated three axial process that closely resembles mammalian embryogenesis. Moreover, gastruloids can develop several organ precursors simultaneously and thus constitutes important improvements over conventional single-tissue organoids. To harvest the potential of gastruloid technology we will first implement large sequencing and imaging experiments to optimize the developmental trajectory of gastruloids for organ inductions. We will then build these datasets into a multimodal data matrix to identify gastruloid candidates for cardiovascular and foregut development. Specifically, we will identify candidates that show strong vasculogenesis as candidates for later vascularisation by anastomose with endothelial cells.

A key problem in Mental Health is that up to one third of patients suffering from major mental disorders develop resistance against drug therapy. However, patients showing early signs of treatment resistance (TR) do not receive adequate early intensive pharmacological treatment but instead they undergo a stepwise trial-and-error treatment approach. This situation originates from three major knowledge and translation gaps: i.) we lack effective methods to identify individuals at risk for TR early in the disease process, ii.) we lack effective, personalized treatment strategies grounded in insights into the biological basis of TR, and iii.) we lack efficient processes to translate scientific insights about TR into clinical practice, primary care and treatment guidelines. It is the central goal of PSYCH-STRATA to bridge these gaps and pave the way for a shift towards a treatment decision-making process tailored for the individual at risk for TR. To that end, we aim to establish evidence-based criteria to make decisions of early intense treatment in individuals at risk for TR across the major psychiatric disorders of schizophrenia, bipolar disorder and major depression. PSYCH-STRATA will i.) dissect the biological basis of TR and establish criteria to enable early detection of individuals at risk for TR based on the integrated analysis of an unprecedented collection of genetic, biological, digital mental health, and clinical data. ii.) Moreover, we will determine effective treatment strategies of individuals at risk for TR early in the treatment process, based on pan-European clinical trials in SCZ, BD and MDD. These efforts will enable the establishment of novel multimodal machine learning models to predict TR risk and treatment response. Lastly, iii.) we will enable the translation of these findings into clinical practice by prototyping the integration of personalized treatment decision support and patient-oriented decision-making mental health boards.