NANOSTEM: An in-depth mechanistic study on how NANOparticles interfere with cell cycle dynamics and developmental processes in STEM cells (R-12787)

Nanoparticles (NPs) have become ubiquitous in our everyday lives. They are present in cosmetics, household products, food additives and pharmaceuticals. NPs are either intentionally added to products (e.g. silver or titanium dioxide NPs), or fragment from larger materials due to weathering processes in the environment (such as micro-and nanoplastics). The numerous in vitro and in vivo studies conducted to assess the effects of NPs mainly focused on spherical NPs. In addition, they often lack an in-depth mechanistic understanding of the interplay between physicochemical characteristics of the NPs and their effects. In this project, we aim to explore the relationship between NP properties such as surface, shape and size and their underlying modes of action. We will specifically focus on cell cyclerelated effects, as NPs are a risk for developing tissues and organisms. To properly link particle characteristics with kinetic uptake profiles and dynamic cellular events, we will work with an in vitro setup using human mesenchymal stem cells. Cross-OMIC approaches will be used to cover and integrate all biological levels. Causal relations and sequences of events will be investigated further using state-of-the-art imaging techniques and functional interfering. Such a detailed understanding of NP toxicity is a necessary first step in function of future risk assessment strategies, f.e. as a part of properly defined adverse outcome pathways.

Keywords:Developmental Toxicity, Mechanisms of action, Nano- and microplastics, Nanoparticle characterization, Nanoparticles, Uptake

Disciplines:Metrology, Molecular and cell biology not elsewhere classified, Other environmental sciences not elsewhere classified, Nanomaterials, Toxicology and toxinology not elsewhere classified