BACKGROUND

Global contamination of soil and aquatic ecosystems by pharmaceutical and microbiological pollutants (such as antimicrobial-resistant microorganisms and/or pathogens) raises severe concerns about impacts on ecosystem health and repercussions on humans and animals. Preserving ecosystems from adverse ecotoxicological effects of pharmaceuticals and their transformation products, and limiting the environmental spread of antimicrobial resistance and pathogens is imperative to reach several UN Sustainable Development Goals as well as the European Green Deal, Water Framework Directive and Biodiversity Strategy for 2030. In this context, the main scientific objective of Pharm-ERA is to develop and implement innovative concepts, methods and strategies to improve the monitoring and assessment of the environmental effects and risks of pharmaceuticals, their transformation products, antimicrobial resistances and pathogens from terrestrial to aquatic environments. The ultimate goal is to provide scientific evidence and expertise to contribute to reducing the environmental spread and impact of these chemical and microbiological contaminants and to preserve microbial diversity and functions across the soil-water-sediment continuum.

DESCRIPTION OF THE PhD PROJECT

On river rocks and solid substrates, complex microbial communities are developing. These communities, also known as periphyton, harbours thousands of different species: microalgae, cyanobacteria, bacteria, hyphomycetes, protists, etc., and play an essential role in headwater streams, ensuring primary production and nutrients recycling. Chemical contaminants, among which pharmaceutical residues, have been shown to modify microbial structure and deteriorate microbial functions. In this context, the main aim of this PhD is to identify and validate metabolic biomarkers of periphyton response to pharmaceuticals and to link those biomarkers with potential further changes in microbial functions. Therefore, Zahra will :
1- establish functional sensitivity thresholds for classical functions in periphyton exposed to selected pharmaceuticals from different therapeutics classes,
2- identify early metabolomics signature of periphyton exposure below the functional sensitivity thresholds previously determined,
3- investigate the influence of selected confounding factors on early metabolomics signatures and finally
4- validate metabolomics biomarkers for periphyton exposed to the selected pharmaceuticals.
To do so, Zahra will conduct experimental studies in micro and mesocosms setups allowing to mimic river environment under controlled conditions. A first screening of periphyton functional response (photosynthetic efficiency, extracellular enzymatic activities, respiration, etc.) to pharmaceuticals will be done on about 15 pharmaceuticals including antibiotics (e.g. sulfamethoxazole), non-steroidal anti-inflammatory drugs (e.g. diclofenac). Thereafter, metabolomic response to selected pharmaceuticals will be investigated along exposure (from hours to several weeks) by LC-HRMS and chemometric data analyses (e.g. multivariate analyses, trend analysis) to identify relevant signals according to pharmaceuticals exposure. Specificity of those identified signals to pharmaceuticals will be tested by investigating periphyton metabolome dynamics under variable confounding factors (e.g. temperature, drought…). Finally innovative data analyses (priorisation of signals by chemometrics tools, meta-analysis...) will be used to compare the different metabolomic profiles obtained and identify key metabolites involved in pharmaceuticals response, i.e. biomarkers. Zahra will work in close collaboration with Louis (UFZ, Germany) to better link metabolomic responses with other -omics level (e.g. metatranscriptomics or metaproteomics) and microbial functions.