10th International Aerosol Conference
September 2 - September 7, 2018
America's Center Convention Complex
St. Louis, Missouri, USA

Abstract View


Connecting the Dots in Nanotoxicology: From the Bio-Nano-Interface to Adverse Health Effects

Stefano Poggio, David Power, Hender Lopez, VLADIMIR LOBASKIN, School of Physics, University College Dublin

     Abstract Number: 1733
     Working Group: Aerosols and Health - Connecting the Dots

Abstract
A definitive conclusion about the dangers associated with human or animal exposure to a particular airborne nanomaterial (NM) can currently be made upon complex and costly procedures including complete NM characterization with consequent careful and well-controlled in vivo experiments. A significant progress in the ability of the robust nanotoxicity prediction can be achieved using modern approaches based on the one hand on systems biology and on the other hand on statistical and other computational methods of analysis. Without the mechanistic understanding of the toxicity, one can only rely on statistical correlations between the NM properties and the toxicity endpoints. Thanks to the development of systemic approaches to analysis of biological systems (systems biology) and new methods of characterization and data generation in toxicology in the recent years, we are now in a position to make a step forward from the black-box-type statistical approaches and formulate a new paradigm in the toxicology – a mechanism-aware NM toxicity screening. We contend that the game-changing screening approach should be based on the detailed understanding of the response of the organism to exposure to NMs from the initial contact to the adverse outcome. To recover the mechanistic picture, we developed a research programme which includes in-vivo, in-vitro and in-silico studies to address main respiratory toxicity pathways, identify the mechanistic key events of the pathways, and relate them to interactions at bionano interface via careful post-uptake NM characterisation and molecular modelling, which is now funded through EU H2020 SmartNanoTox project.

In the SmartNanoTox project, we propose to construct a predictive model for gauging the toxicological and biological impacts of NMs using

• in vivo toxicity pathways for NMs that are of regulatory importance
• molecular initiating events and key events steering the toxicity pathways finally leading to an adverse outcome
• molecular mechanisms of NM involvement in these KEs
• structure and content of NM-biomolecule complexes after NM uptake.

The key step in the development of the smart screening approach is to combine the systems biology analysis of the responses of organisms to the NM exposure, resulting in a clear identification of the resulting pathways and key events, with the analysis of the whole chain of bionano interactions involving the NM inside the organisms.

The project team developed a number of innovative solutions to elucidate the key interactions involving airborn NMs. In this talk, I will present the project ideology and results to date.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 686098.