18HLT02 AeroTox: Measurements for mitigatin adverse health effects from atmospheric particulate pollutants

• Unité de recherche: METAS
• Numéro de projet: F-5235.30113

Mots-clé (Anglais)

Atmospheric aerosols, cell cultures, chemical models, cytotoxicity, lung organoids, optical microscopy, oxidative potential, particulate matter, inflammatory response.

Description succincte (Anglais)

Atmospheric particulate pollution has been linked to a broad spectrum of adverse health effects including respiratory problems, cardiovascular diseases, cancer and dementia. These effects depend not only on physical, but also on chemical properties of airborne particulate matter (PM) though to date it has proven difficult to disentangle the relative contribution of PM constituents to the reported population-level health effects. To address this issue this project will use "tailored" reference aerosols, combined with high-resolution optical imaging of exposed cells and state-of-the-art cell analysis methods to study the cytotoxic effects of airborne PM in vitro. This will be done in a systematic way to help inform which PM metrics are associated with the induction of toxic mechanisms so that they can then be linked to specific health effects.

This is a joint research project carried out in the framework of the European Metrology Programme for Innovation and Research (EMPIR) (see:http://www.euramet.org/research-innovation/empir/). The EMPIR initiative is co-funded by the European Unions's Horizon 2020 research and innovation programme and the participating states. METAS is one of the project partners in the project.

Objectifs du projet (Anglais)

The overall goal of this project is to identify correlations between particle component/properties (metrics) with adverse outcome pathways that are associated with the induction of acute and chronic health effects within the European population. This will be delivered through the development of a new method for studying in vitro cytotoxicity based on the use of "tailored" synthetic ambient aerosols combined with high-resolution optical imaging and state-of-the-art cell analysis methods. The specific objectives of the project are:

1. To develop a stable and reproducible laboratory-based source of well-controlled and chemically defined, synthetic reference aerosol mixtures that mimic real ambient aerosols at high concentrations (at around the limit values of the EU Air Quality Directive and up to a few mg/m3). The aerosol properties should be tunable and the source should be coupled to an oxidation flow reactor (OFR) to mimic atmospheric photochemical "ageing". To improve traceability for the physical and chemical characterisation of the synthetic aerosols using EU reference methods (target uncertainty in mass concentration 15 %, number concentration <15 %, analysis of major chemical components <15 %). Moreover, to quantify uncertainties for emerging techniques, such as Aerosol Mass Spectrometry (AMS) for chemical analysis and Brunauer–Emmett–Teller (BET) for surface area analysis and develop new approaches to ensure reproducibility and quality assurance.
2. To apply novel methods for cell exposure at the air-liquid interface (ALI) in order to mimic and quantify the effects of the in vivo aerosol inhalation routes. To study phenotypic effects using lung organoids. To compare these novel methods with the conventional cell-exposure techniques relying on submerged cell systems, where aerosol particles are collected in water with high-volume samplers.
3. To assess how the composition of the collected aerosols and their ageing impacts on their acellular and cellular oxidative characteristics, both in simple chemical models simulating human respiratory tract lining fluids (in health and disease) and in representative cell lines maintained under near physiologic conditions. To evaluate adverse outcome pathways using proteomics and transcriptomics (high throughput sequencing), to examine known causal pathways, such as pro-/anti-inflammatory responses, cytotoxicity and genotoxicity, as well as novel ‘component-specific’ pathways. The project will work toward improved, validated protocols for harmonising/standardising cell analysis studies, as well as on the integration of multi-omic approaches for statistical analysis of complex data sets on a European level.
4. To push the frontiers of optical imaging and biological image analysis to quantify the effects of particle uptake on single cells and cell populations by using various types of optical microscopy including confocal, structured illumination, light sheet and fluorescence lifetime imaging.
5. To facilitate the take up of the technology and measurement infrastructure developed in the project by the measurement supply chain (accredited laboratories, instrumentation manufacturers), standards developing organisations (CEN, ISO) and end users (e.g. hospitals and health centres).