The Human Exposome Project: a toolbox for assessing and addressing the impact of environment on health Applicants should take advantage of the last decade's rapid technological advances which have opened up new opportunities to collect, combine and analyse large data sets offering new possibilities to understand the contribution of environmental factors to the global health burden of common chronic diseases. Proposals should use innovative approaches to the systematic and agnostic identification of the most important environmental risk factors for the development of major NCDs across the life course (including in utero), leading to preventive interventions at the individual, group or population level and contribute to sustainable healthcare. Well-designed retrospective epidemiological studies may be included and proposals may envisage the creation of a prospective Europe-wide exposomics cohort and biobank, integrating behavioural, socio-economic factors and clinical records.The following components should be considered: agnostic evaluation of the role of multiple and unknown exposures; assessment of individual exposure to multiple stressors; sensors that combine external exposure and health data measurements; integration of external exposome data with cross-omics responses and (epi)genetic data; systematic evaluation and simulations of the health impacts; socio-economic modelling and econometric analysis including ethical and sex/gender aspects where relevant; better data mining tools, including advanced statistical analysis of complex data and high-performance/high throughput computing and storage; a long-term host and a single shared data infrastructure, taking into account existing structures and ensuring open access to data generated.Innovation and connections with industry are expected in the areas of sensor development (external exposome), omics technology and novel biomarker development (internal exposome), bioinformatics, and data processing and management. Proposals are expected to respond to a persistent or long-standing policy/regulatory need where the exposome approach would be useful to solve a scientific issue to underpin better regulation now or in the future (examples: indoor and outdoor air quality, waste, occupational health, noise).In order to establish an overarching Human Exposome Project, an overall coordination mechanism between the projects funded will be required and will be added at the grant preparation stage to all selected proposals as a common work package. Grants awarded under this topic will be complementary. The respective options of Article 2, Article 31.6 and Article 41.4 of the Model Grant Agreement will be applied.The Commission considers that a proposal requesting an EU contribution between EUR 8 to 12 million would allow this specific challenge to be addressed appropriately. Nonetheless, this does not preclude submission and selection of proposals requesting other amounts. Despite the general acknowledgement by the scientific community that 'Genetics load the gun but environment pulls the trigger'[[Dr. Francis Collins, Director of the U.S. National Institutes of Health (NIH) www.ncbi.nlm.nih.gov/pmc/articles/PMC2675383]] when it comes to the causation of major non-communicable diseases (NCDs)[[ http://www.who.int/mediacentre/news/releases/2016/deaths-attributable-to-unhealthy-environments/en/]], there is persistent uncertainty as to the global burden of disease attributable to environmental (including life-style and climatic) factors, including healthcare costs and negative economic impact. Deciphering the human exposome[[The concept of the exposome refers to the totality of environmental exposures (diet, lifestyle, occupational and environmental factors) from conception onwards, including its external and internal components.]] is a novel way of addressing the challenge to improve health and reduce the overall burden of disease. This will require improved knowledge of health risks, including combinations of several risk factors, and the mechanisms by which they affect health at different stages throughout the life course, including exposures in foetal life. Effective preventive action will need to be designed, building on knowledge of various risk factors, including exposure to pollutants in daily life, individual behaviour and the social context, taking into account gender issues.Developing a Human Exposome Project would present a fundamental shift in looking at health, by moving research away from ‘one exposure, one disease’ understanding to a more complex picture upon which to build solid, cost-effective preventive actions and policies in the future. It would respond to the need for more complete and accurate individual-level exposure data in order to estimate the largely unknown environmental component of NCDs. Innovation in environmental health sciences, in particular for external and internal exposure assessments and data management. Enabling researchers and policy makers to continuously include new knowledge in the policy making processes by using the toolbox to generate data and information. Better prediction of disease risk by acquisition of new knowledge on the influence of external exposures on biological pathways at different life-stages and identification of early signs of health damage caused by environmental factors.