The quality of human (and veterinary) health care systems substantially depends on key innovations. Often, these were driven by the field of physics, followed by interdisciplinary and inter-sectorial actions in engineering, chemistry, biology, and medicine, such as X-rays in medical diagnostics, ionizing radiation in cancer treatment, and femtosecond lasers for precision surgery. Medical gas plasma technology was introduced to human health care a decade ago. Today, accredited medical plasma devices are in daily operation in dozen dermatology centers in middle Europe to improve wound healing. In addition, physical plasmas were shown to inactivate cancerous cells. Actinic Keratosis is a skin disease affecting millions of Europeans and making them prone to invasive and deadly skin cancer. Many of the available treatment options are associated with low efficacy, pain, risks, and/or high costs. Medical gas plasma technology is operated at body temperature and applied painlessly, cost-effectively, and without notable side effects. Gas plasma has been suggested to be active on high-grade cancer cells, but its activity against premalignant cells, as in Actinic Keratosis, is unknown. By using beyond state-of-the-art plasma multijet technology, the primary technical objective of PlasmACT – Plasma against Actinic Keratosis – is to support skin cancer prevention by medical gas plasma therapy of Actinic Keratosis. PlasmACT does so by educating a new generation of application-oriented scientists that are exposed to questions and findings from different scientific fields (interdisciplinary from physics over chemistry and biology to medicine) and capable of addressing questions in view of both academic as well as business needs (inter-sectoral) while incorporated in a vivid and productive environment across borders and cultures (international).

Healthspan (the life period when one is generally healthy and free from serious disease) depends on nature (genetic make-up) and nurture (environmental influences, from the earliest stages of development throughout life). Genetic studies increasingly reveal mutations and polymorphisms that may affect healthspan. Similarly, claims abound about lifestyle modifications or treatments improving healthspan. In both cases, rigorous testing is hampered by the long lifespan of model organisms like mice (let alone humans) and the difficulty of introducing genetic changes to examine the phenotype of the altered genome. We will develop C. elegans as a healthspan model. Already validated extensively as an ageing model, this organism can be readily modified genetically, and effects of environmental manipulations on healthspan can be measured in days or weeks. Once validated as a healthspan model, it can be used for an initial assessment of preventive and therapeutic measures for humans, as well as for risk identification and the initial evaluation of potential biomarkers. It will also prove useful to study interactions between genetic and various environmental factors.

Understanding mechanisms underlying comorbid disorders poses a challenge for developing precision medicine tools. Psychiatric disorders are highly comorbid, and are among the last areas of medicine, where classification is driven by phenomenology rather than pathophysiology. We will study comorbidity between the most frequent psychiatric conditions, ADHD, mood/anxiety, and substance use disorders, and a highly prevalent somatic disease, obesity. ADHD, a childhood-onset disorder, forms the entry into a lifelong negative trajectory characterized by these comorbidities. Common mechanisms underlying this course are unknown, despite their relevance for early detection, prevention, and treatment. Our interdisciplinary team of experts will integrate epidemiologic/genetic approaches with experimental designs to address those issues. We will determine disease burden of comorbidity, calculate its socioeconomic impact, and reveal risk factors. We will study biological pathways of comorbidity and derive biomarkers, prioritizing two candidate mechanisms (circadian rhythm and dopaminergic neurotransmission), but also leveraging large existing data sets to identify new ones. A pilot clinical trial to study non-pharmacologic, dopamine-based and chronobiological treatments will be performed, employing innovative mHealth to monitor and support patients’ daily life. Integration of findings will lead to prediction algorithms enhancing early diagnosis and prevention of comorbidity. Finally, we will screen to repurpose existing pharmacological compounds. Integrating complementary approaches based on large-scale, existing data and innovative data collection, we maximize value for money in this project, leading to insight into the mechanisms underlying this comorbidity triad with its huge burden for healthcare, economy, and society. This will facilitate early detection and non-invasive, scalable, and low-cost treatment, creating opportunities for substantial and immediate societal impact.