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Exploring the PFAS alternatives-induced immunotoxicity and impact on intercellular communication.

Project description

Immunotoxicity of emerging alternatives to everyday chemicals

Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic compounds with known immunotoxic effects. As regulatory restrictions increase for PFAS, alternatives such as perfluoroundecanoic acid (PFUnDA) are emerging, though their biological impacts remain unclear. Supported by the Marie Skłodowska-Curie Actions programme, the EPIC project investigates how long-term PFUnDA exposure affects immune regulation and intercellular communication in zebrafish. The study focuses on extracellular vesicles (EVs), nanosized particles produced by all cells, carrying molecular cargo that reflects the physiological state of their cells of origin. By evaluating changes in immune system-related gene expression and EV microRNA profiling, the project aims to uncover mechanisms of PFUnDA-induced immunomodulation and assess the potential of EVs as biomarkers for chemical exposure in aquatic ecotoxicology.

Objective

Per- and polyfluoroalkyl substances (PFASs) are emerging environmental contaminants which are highly persistent in the environment with multiple hazardous properties including immunomodulation/immunotoxic potency. Human exposure to PFASs has been associated with various immune-mediated diseases and outcomes. Recently the European Chemicals Agency (ECHA) called for a gradual ban of over 10,000 PFAS compounds in Europe. As concerns grow about the persistence and toxicity of PFAS, the market has shifted towards new PFAS alternatives, however, little is known about the potential risks of these newer chemicals. PFASs have now widely been replaced in many consumer products with PFASs with longer carbon-chains, like perfluoroundecanoic acid (PFUnDA). Rising exposure levels of PFUnDA has been already observed and it was reported previously to have negative effect on the immune system in vitro and in vivo.
Blood plasma transports mRNA that modulate immune responses and also extracellular vesicles (EVs) that play key role in intercellular communicationthat and can transport biologically relevant cargo, including microRNAs (miRNAs), and may partly mediate the effects of pollutants on the immune system.
This project aims to determine how new PFAS alternatives affect the immune system in long term exposure. To fully understand the mechanisms and to address the multifaceted nature of chemical induced immunotoxicity, the study focuses on changes of key mRNA biomarkers related to the immune system and on the EV-miRNA cargo of extracellular vesicles in long term PFUnDA exposure. Our goal is to develop a multi-biomarker palette identifying key mRNAs and EV-miRNAs in zebrafish to screen novel chemicals for their immunotoxic potency, that is high throughput, quick and easily measured from blood.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

Masarykova univerzita
Net EU contribution
€ 166 278,72
Address
Zerotinovo namesti 9
601 77 Brno
Czechia
Region
Česko Jihovýchod Jihomoravský kraj
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data