A dysfunction of cells lining the inner walls of blood vessels, i.e. the endothelium, is the primary cause of many lifestyle related diseases. According to the WHO, those diseases accounted for 60% of all deaths worldwide in 2005. Tailor-made diagnostic tools for early and reliable identification of endothelial dysfunction are urgently needed both in fundamental research and clinical routine, respectively. The Marie Skłodowska-Curie action LOGIC LAB objects to develop and characterize innovative molecular logic gates that can be applied as advanced diagnostic tools for parallel analyte sensing in live mammalian cells. Thereby, providing a unique method to discover endothelial dysfunction and the onset of diseases much easier and earlier than so far. LOGIC LAB creates a multi-faceted and multi-sectoral research environment for the next generation of scientists in order to establish a novel type of molecular logic sensors that reliably operate in biological media – a crucial requirement for their application i.e. as rapid and easy-to-handle tools for intracellular diagnostics. With excellent cross-disciplinary scientific and complementary training provided in the network, we aim to educate highly-skilled young scientists in the fields of chemistry, physics and biology, who will significantly strengthen the international research community in the domain of molecular logic sensing. Thus, in the long term, LOGIC LAB aims to finally bridge the gap between lab bench and biological or medical practice. It is this gap, that so far prevents a wide-ranging use of existing molecular logic gates e.g. for the diagnosis of lifestyle-associated diseases.

The vision of the ONTOX consortium is to provide a functional and sustainable solution for advancing human risk assessment of chemicals without the use of animals in line with the principles of 21st century toxicity testing and next generation risk assessment. Specifically, ONTOX will deliver a generic strategy to create innovative new approach methodologies (NAMs) in order to predict systemic repeated dose toxicity effects that, upon combination with tailored exposure assessment, will enable human risk assessment. This strategy can be applied to any type of chemical and systemic repeated dose toxicity effect. However, for proof-of-concept purposes, focus will be put on 6 specific NAMs addressing adversities in the liver (steatosis and cholestasis), kidneys (tubular necrosis and crystallopathy) and developing brain (neural tube closure and cognitive function defects) induced by a variety of chemicals, including from the pharmaceutical, cosmetics, food and biocide sectors. The 6 NAMs will each consist of a computational system based on cutting-edge artificial intelligence (AI) and will be primarily fed by available biological/mechanistic, toxicological/epidemiological, physico-chemical and kinetic data. Data will be consecutively integrated in physiological maps, quantitative adverse outcome pathway networks and ontology frameworks. Data gaps, as identified by AI, will be filled by targeted state-of-the-art in vitro and in silico testing. The 6 NAMs will be evaluated and applied in collaboration with industrial and regulatory stakeholders in order to maximise end-user acceptance and regulatory confidence. This is anticipated to expedite implementation in risk assessment practice and to facilitate commercialisation. ONTOX will have a deep and long-lasting impact at many levels, in particular by consolidating Europe’s world-leading position regarding the development, exploitation, regulation and application of animal-free methods for human risk assessment of chemicals.