A Priority Programme of the Deutsche Forschungsgemeinschaft

In order to understand and categorize the mechanisms for nanoparticle toxicity, information is needed on the response of biological systems to the presence of NPs of varying size, shape, surface properties and chemical composition, as well as the temporal fate of the nanoparticles that are subject to translocation and degradation processes. The typical pathway within the organ and/or cell, which may be the result of either diffusion or active intra- and intercellular transport, is also of relevance.

A major emphasis of the current programme is also on the impact of NPs on the fundamental biological functions of cell organelles, cells and cell systems. The selected objectives to advance our understanding include the effects of NPs on the induction of oxidative stress, the disturbance of the cellular redox-balance and how these translate into pro-inflammatory processes, the cell signalling pathways and the genome integrity. The following aspects are to be investigated
The effects of NPs on the induction of cellular oxidative stress and on the disturbance of cellular redox-homeostasis.
The impact of NP on redox-sensitive cell signalling pathways and on genome integrity in association with cellular function and response including cell cycle arrest, proliferation, and apoptosis.
The evaluation of the generation of reactive oxygen species (ROS) and oxidative stress is envisaged to be achieved by applying a broad spectrum of assays including fluorescence microscopy, detection by flow-cytometry, as well as by analysis of oxidative stress responses such as cellular gluthathione-depletion, protein/DNA oxidation and activation of redox-sensitive signalling pathways. Interactions and effects of NPs with/on mitochondria and the nucleus will be performed using morphological/microscopical assays such as electron microscopy, confocal microscopy and FRET microscopy. Concomitant analyses of mitochondrial function and genomic DNA integrity using various molecular biological approaches is also suggested.

2. Transition of nanoparticles into and the interaction with the biolog