1. Pre- and perinatal origins of chronic disease

To decipher effects of periconceptional, pre-, peri- and postnatal insults on the origins of chronic diseases INTERPLAY will combine its large expertise in translational research. INTERPLAY PIs work with well characterized animal models to assess insults in a critical window of development on the development of chronic diseases [1]. These adverse influences are intimately associated with premature birth, which together with ensuing life-saving treatments (e.g. oxygen supply, mechanical ventilation) can lead to long-term neurological and pulmonary sequelae. Our research has entailed landmark discoveries as the origins of chronic neurodevelopmental, metabolic, and pulmonological diseases.

2. Transition to chronic diseases

Early influences in childhood affect the risk for the development of chronic diseases, e.g. chronic inflammatory diseases, such as obesity, high-grade inflammation related rheumatic diseases, immune-mediated kidney, liver and inflammatory bowel diseases, as well as psychiatric diseases such as anorexia nervosa. Even pediatric hematologic malignancies belong to this spectrum. Gene-environment interactions determine the susceptibility towards these conditions, their manifestation or chronification. Genetically susceptible individuals can develop chronic non-/inflammatory or malignant disease depending on (environmental/non-/infectious) hits. While many of the genetic determinants for susceptibility are identified, most of the environmental risk factors triggering transition to chronic disease remain elusive. To close this gap of knowledge INTERPLAY will establish an (early) risk assessment to define common denominators of chronic diseases and to predict time points of disease-transition to chronicity.

3. Gene-environment interaction in tumor development and treatment

A prerequisite for advancing the current limited understanding of the origins of chronic diseases is the elucidation of mechanisms underlying the interaction of genes and environment, e.g. nutrition, metabolism, or the microbiome. The principal investigators have outstanding records in investigating gene-environment interactions and are involved in numerous national and international research consortia.

4. Interplay of somatic and mental health

An accumulating body of evidence indicates that several somatic and mental disorders are biologically linked. INTERPLAY has selected a team of world-renowned experts in the fields of cognitive, affective, and social development and mental disorders, including genetics, neuroimaging, clinical neurophysiology, phenotyping, and therapeutic research. PIs Hebebrand and Hinney address complex mental disorders including polygenic risk scores [22]. Both are, along with PIs Herpertz-Dahlmann and Konrad, collaborators of large international consortia for Genome wide association studiesWAS (e.g. GIANT, PGC). Together with Aachen and Bochum, the Dept. of Child and Adolescent Psychiatry in Essen hosts the German anorexia-registry and is with Cologne part of the ESCA and CARE FAM NET.

5. Prevention and health care services research

INTERPLAY comprises the following five research areas:

1. Translational studies using mouse and human models to gain mechanistic insight into lifestyle interventions (e.g. exercise, nutrition) during pregnancy
2. Perinatal health services research to improve care of very-low-birth-weight infants in NICUs (HSR-NICU);
3. Development of preventive care and interventions in real-life settings regarding lifestyle factors (e.g. sedentary behavior, psychosocial well-being) and development of metabolic diseases as well as improving transition
4. Improvement of treatment and schooling by reducing barriers to implement innovations in care organizations and ensuring technology-based assisted communication
5. Analysis of the effects of psychosocial interventions in pre-schools and schools with digitally based self-help interventions (web-based parent training, smartphone apps) to prevent mental disorders, e.g. ADHD, and non-adherence of e.g. transplanted patients.

A unique characteristic of INTERPLAY is the involvement of the BZgA, a federal governmental agency and research institution for national health communication, prevention, and health promotion. The BZgA provides well-accepted websites with high reach into the population to ensure translation of INTERPLAY’s and also other DZKJ partner-sites’ research findings into multi-lingual health communication material for parents, families, and the professional workforce across sectors. It has the federal task to identify and develop prototype models of population- or setting-level interventions aimed at promoting child and adolescent health. As a large stakeholder, it acts across health-relevant sectors on the municipal, federal, and state levels, to translate, transfer, and disseminate research into practice.

6. Innovative medical technologies

Innovative medical technologies are crucial for supporting children suffering from chronic diseases. By the integration of the Helmholtz-Institute for Biomedical Engineering and the Research Centre Jülich and the artificial intelligence AI Future lab (Essen), INTERPLAY holds excellent infrastructures and specific expertise for facing technological and data science challenges:

• medical technology, engineered contactless monitoring and developed electrical impedance tomography to visualize lung ventilation independent of patient cooperation
• innovative products/implants for pediatric use, e.g. growth-capable implants such as heart valves (pulmonary and aortic valves), and vital endotracheal/-bronchial stents (PulmoStent)
• data science in development of innovative digital technologies for clinical and neuroscience applications. Technologies developed at the INM-7 led by him include the digital biomarker platform JuTrack (https://jutrack.inm7.de/) allowing for home-based data collection using patients’ own smart devices
• data management infrastructure DataLad (https://www.datalad.org/) for integration of large multimodal data resources
• digitalization and AI projects in different patient groups (KTX360° and NephroDigital) and the development of Apps as “Virtual Reality” systems for reducing anxiety and stress in children (“Pingunauten-Trainer” for MRI, Frühstart App, TELEKASPER, video consulting)
• digital applications for the assessment and treatment of mental disorders
• reality-directed physiotherapy to children with cerebral palsy and develops a Video-based outpatient follow-up care system and App-based training for children following preterm birth (e.g. hand-writing) to increase patient adherence and provide early interventions

In summary, INTERPLAY provides a unique constellation of medical, research, and translational expertise of 38 PIs in six research areas.