CE34 - Contaminants, écosystèmes et santé

Proteomics and Lipidomics Approaches for understanding molecular mechanisms of environmental chemical toxicity in conjunction with lipid metabolism in Gammarus fossarum during reproduction cycle – PLAN-TOX

Submission summary

Aquatic ecosystems are persistently exposed to environmental stressors such as chemical micropollutants from natural environment or anthropogenic activities. These chemical contaminations may result in alterations of the internal biochemical homeostasis of the aquatic organisms, noticeable at the omics scale. The major limitation in the mechanistic knowledge of environmental chemical toxicity effects on aquatic organisms is the absence of molecular information notably at the genome wide scale in environmentally relevant species. The “omics” technologies – Transcriptomics, Proteomics, Lipidomics, Metabolomics to name a few – offer great promises to help to elucidate molecular responses to exposures in aquatic organisms during specific and vulnerable life cycle stages. Lipid metabolism is the major fundamental metabolic pathway producing energy in animals. In crustacean, lipids play a pivotal role in vulnerable stages like molting, reproduction, development. Recently, it has been shown that chemical compounds interfering with lipid metabolism, recognized as obesogens like tributyltin, mislead the distribution and the synthesis of lipids in the non-target and model organism Daphnia magna. Moreover, pharmaceutical drugs used for hypercholesterolemia to lower cholesterol and triglycerides concentrations like pravastatin or bezafibrate have been detected in sewages. Another study showed that simvastatin exposure in the amphipod Gammarus locusta disturbed the reproduction and population growth at the ng/L range. To understand and predict the effects of toxic exposures, it is crucial to identify the affected metabolic networks. Statins are among the most broadly used pharmaceuticals worldwide and is therefore of emerging environmental concerns. This medication inhibits selectively the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) involved in the synthesis of mevalonate, a precursor of sterols including cholesterol. We hypothesize that lipid metabolism may turn out to be the drug-induced toxicity target in aquatic species. However, we are facing a lack of crucial knowledge about the relationships between the abundance of lipid species, the activation/inhibition of signaling and/or biosynthesis pathways and the observed phenotypes. The project PLAN-TOX aim to gain a mechanistic understanding of toxic effects of hypolidiaemia drugs (statins and fibrates) on the sentinel organism G. fossarum.
We are proposing to develop and apply an innovative multi-omics approach in ecotoxicology, including (i) the functional proteome and lipidome mapping in the sentinel organism G. fossarum before and after exposure, (ii) the development of methods for the integrative analysis of multi-omics data. G. fossarum is a widely developed sentinel species in ecotoxicology or environmental monitoring and is one of the ecologically relevant species for which we can evaluate the toxicity on different development stages and reproductive cycles. This project will allow to better understand molecular plasticity of energetic metabolism and to identify proteins and lipids involved in physiological changes/responses related to exposure.

Project coordinator

Madame Sophie Ayciriex (Institut des Sciences Analytiques)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

ISA Institut des Sciences Analytiques

Help of the ANR 190,437 euros
Beginning and duration of the scientific project: December 2018 - 36 Months

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