Mercury (Hg) is an important pollutant distributed all over the world, in the atmosphere, onto continents and inside oceans. It can be accumulated and bioamplificated in aquatic food chains where concentrations of its main toxic form, monomethylmercury (MMHg), reach level potentially dangerous for human health. The main goal of the RIMNES-Project is to propose innovative geochemical and biological tools at the link between Environment and Health. Recent interest leads us to develop a new tracer tool which might characterize the different types of Hg exposure, not only in developed countries but also in emerging regions. The first objective is to understand Hg processes and transformation in the environment. Very recently, stable isotope signatures have been recognized as a powerful tool to trace processes and sources of Hg. We propose to use this method to analyze environmental samples in two contrasted regions impacted by Hg polluting activities: 1) in French Guiana, along the Oyapock R. where numerous artisanal gold-mining activities lead to recurrent environmental, social and economic pressure; and 2) in the Guizhou Province known as the “mercury capital” of China. High Hg concentrations in human hair of populations living in the selected areas have already been evidenced and attributed to food exposure (fish diet in French Guiana and rice consumption in China). Our recent studies have demonstrated that Hg isotope signatures in human hair provide qualitative and quantitative information on MMHg sources related to human exposure via diet. A focus on the trophic chain, through bedrock, sediments, biofilms, fish and rice analyses, will permit to understand Hg isotopes fractionation before absorption of MMHg by human. Additionally, an experimental study, consisting in feeding adult male zebrafish with contaminated food (MMHg and inorganic Hg), will allow us to highlight Hg isotopes fractionation in their organs (brain, liver and muscle) by metabolic processes. The second objective is to better understand the mechanisms of action of Hg species in fish and in human cells. MMHg contamination will be analyzed from aquarium and Oyapock river fish through genomic and cell biology approaches. The study will first focus on gene cluster expression relevant to metabolic pathways such as detoxification, oxidative stress, apoptosis and newly identified Notch pathway. This genomic study will be accompanied by the setting up of human cell lines dedicated to the analysis of the newly identified MMHg-dependent Notch pathway. Identified biomarkers will allow designing new informative genomic and biomarker-based cell assays. It is important to notice that the genomic and cell based studies dealing with MMHg-dependent Notch pathway activation will provide the very first data available on both fish and human models. At the end of the project, biomarker assays will be delivered in high throughput format in order to provide biomonitoring tools for in situ MMHg toxicity measurement. The strengths of this project are related to 1) its methodology combining experimental studies with natural environment sampling, 2) its originality by coupling geochemical with biological innovating methods to trace Hg sources and effects on living organisms in contaminated environments and 3) its exclusivity as we are the unique research group in the world working on the Hg isotope fractionation in human tissue.