Mercury (Hg) pollution is considered a major environmental problem. Due to its extreme toxicity, Hg has been recently included in the list of the top ten chemicals of major public health concern by the World Health Organization. Once released in the environment, it is transformed, principally in aquatic ecosystems, by microorganisms into the neurotoxic methylmercury. Its hazardous effect is biomagnified through the trophic chain, resulting in serious social and health effects. However, Hg metabolic pathways in biota remain elusive. Its understanding is crucial to elucidate its (eco)toxic effect as well as its biogeochemical cycle. Bioavailability, mobility and toxicity of an element are dependent of its chemical forms. Hg binding with proteins has been evoked as a cause for toxicity and the role of selenium (Se) as antagonist for Hg toxicity is acknowledged but not understood so far. MERSEL is an ambitious and multidisciplinary research project, which main objective is to advance the understanding of Hg metabolic pathways in living organisms paying also attention to its (antagonist) interaction with Se. The project is based on the development of new analytical approaches that combines speciation and natural isotopic fractionation in a unique pattern. Speciation provides valuable information about reactivity and potential toxicity of the metabolites. Complementary, the natural abundance isotopic signature adds a dynamic dimension, comprising the life history of the target element, its (pollution) source and reaction tracking. The resulting (bio)molecular and isotopic signature will be precious in the insight of Hg in biota and its detoxification mechanisms, including its relation with Se. On a long term prospective, this highly innovative methodology could be extended to other metal/loids and push back frontiers in life and environmental sciences related to them. The success of the project is assured by the knowhow in speciation and isotopic analysis and worldwide unique instrumental facilities of the host laboratory. MERSEL will build knowledge on environmental ecotoxicology with a potential application in health science through a multidisciplinary project (biogeochemistry, ecotoxicology and metabolomic). It will contribute to improve the understanding of Hg metabolism and its potential detoxification in fish and marine mammals, which could be used later on as a reference work to study Hg behavior in humans. It has a direct societal impact considering that until now there is a lack of efficient treatment against the toxicity of this pollutant. One of the most important socio-economic benefits is that it will help in setting new guidelines for aquaculture feeding practices to avoid fish contamination with Hg toxic forms and to insure proper bioassimilation of its antagonist, Se. It also aims the establishment for fish and seafood of more realistic mercury toxicity assessment than the current criteria that is limited to the methylmercury content. It has a direct link with aquaculture development preconized by H2020 European program to sustainably exploit and manage aquatic living resources. The aquaculture model fish studied in this project, trout, is representing with salmon the main share by value of aquatic species in world trade (FAO, 2016) and the main fish species produced in France (2nd European producer).