Scientific Strategy

HEALS is organized in a series of interlinked streams of activity focusing on the different aspects of individual assessment of exposure to conventional and emerging environmental stressors and on the prediction of the associated health outcomes. These streams bring together state-of-the-art advances in human biomonitoring and systems biology towards the development of an exposure biology paradigm, exposure monitoring technologies and advanced tools for computational analyses of the exposure-to-effect continuum. In fact, HEALS proposes the functional integration of -omics derived data and biochemical biomonitoring to create the internal exposome at the individual level. These data will be exploited using advanced bioinformatics tools for both descriptive and predictive data mining. HEALS will propose a novel bioinformatics strategy focusing on biomarker fusion, and direct coupling of physiology-based biokinetic models to metabolic regulatory networks derived from -omics analyses. In this way, the internal dose of environmental stressors will be coupled to the alterations they bring about to gene expression, protein-protein interactions and metabolic regulation and plausible hypotheses on the respective pathways of toxicity can be established.

The external exposome will be derived using environmental, occupational and dietary data and model fusion using efficient algorithms for mining existing environmental monitoring datasets and ubiquitous sensing using geo-localized sensors and mobile phones. A key innovation here is the development and optimization of the necessary software apps for data integration and the coupling of these datasets with agent-based modeling incorporating the socio-economic determinants of population exposure to health stressors. Exposomic analysis will focus on critical stages in human life extrapolating to the whole lifespan using Bayesian statistical modeling to construct the integrated individual exposome.

The internal and external exposome data above will be used to derive environment-wide associations between exposure and health. Novel mathematical and computational tools will be used to explore the association between different environmental, genetic and epigenetic determinants and identified biological perturbations and, eventually, disease phenotypes. In addition, using the HEALS methodology, a plausible pathway towards establishing causality in the observed associations between environmental stressors and health status will be tread (see figure 1.1).

The HEALS approach and tools will be put to test through their application in a number of population studies (incl. twins studies) across different exposure settings tackling key health endpoints of the SCALE initiative and the Parma Declaration for both children and the elderly, including allergic respiratory diseases, bronchial asthma, neurodevelopmental and neurodegenerative disease, obesity, and childhood type II diabetes (T2D). The overall population size involved in these studies is up to ca. 335,000 individuals covering different age, gender and socio-economic status groups. The cohorts involved are dispersed across Europe to provide sufficient geographic coverage so as to facilitate drawing conclusions at the EU-wide scale. These cohorts have been carefully selected to comprise twins. The classical twin methods combined with novel technologies represent a powerful approach towards identifying and understanding the mechanisms and pathways that underlie complex traits. In this way, epigenetic modification of both exposure to and effect of co-exposure to chemical, physical and biological environmental stressors throughout a person’s lifetime will be easier to take into account when deducing environmental exposure and health associations.

Based on the results of these population studies, a pilot exposure and health survey (EXHES) will be organized in 10 EU countries to test the applicability of the HEALS approach for EU-wide large population surveys. EXHES will combine a longitudinal and a nested case-control phase to allow for better definition of environmental exposures and better characterization of disease and risk phenotypes over the limited duration of the project, whilst setting the foundation for post-project follow-up. The technological and computational integration proposed in HEALS will be tested through EXHES with regard to both technical feasibility and cost-effectiveness. The lessons drawn from the EXHES pilot survey will provide the basis for drafting scientific advice, protocols and, eventually, guidance for the setting up of a European Health and Exposure Survey, paving the way to EU-wide assessments.

These activities are underpinned by horizontal streams necessary for determining the policy context and networking with the international scientific community as well as developing scientific guidance on exposome-based risk assessment. Widespread dissemination and technology transfer/commercial exploitation of the technological advances assured by the HEALS innovations will be proactively pursued. The HEALS consortium is dedicated to the rapid translation of scientific findings in the environment and health area into actual innovative tools that can enter the market in support of both job and wealth creation as well as cost-effective policy interventions that can mitigate the environmental burden of disease in Europe and worldwide. For this reason, an aggressive knowledge transfer strategy will be followed, setting the delivery of technological and methodological innovation in the environmental health sciences and risk assessment as a key objective of the project. Innovation management will be included in the consortium agreement and a knowledge transfer strategy for HEALS as a whole and for specific parts of the technological tools developed or optimized in the frame of the project will be prepared and implemented from the onset of the work.