NGI - Netherlands Toxicogenomics Centre (NTC)

An applied system biology approach to predict chemical safety


Cancer, the second leading cause of death in the Western world, is primarily caused by genome instability. Genomic instability is usually associated as the result of toxicological interactions between several chemical compounds and the cell DNA content. Nevertheless, there are still many compounds with unclear or unidentified toxicological properties. This is of concern since there is an increase in the number of compounds synthesized by the pharmaceutical, chemical, cosmetic and food industries to which humans might be exposed. Therefore the well-established chemical safety of these substances is of crucial importance to be tested.

This is a project from the Netherlands Toxicogenomics Centre in which several institutions work together to achieve the desired system biology approach. The interaction between the partners will focus in the integration of data generated from several highly sensitive methodologies such as the ones used in genomic, metabolomic, proteomics and bioinformatic areas. In particular this Postdoctoral fellow focuses on the genomic analysis (mRNA and miRNA) from several substances by different in vitro and in vivo models, particularly in the context of liver toxicity. The identification of genes that cause sensitivity for genotoxic carcinogens as well the transcription factor regulated genes by genotoxic compounds is also programmed. Thereafter the in vitro and in vivo findings will be translated to human subjects, in order to determine biomarkers in relevant in vivo models and material of patients exposed to carcinogenic drugs. This will lead to establish mechanism-based high-content in vitro and sensitive in vivo reporter models for the prediction of carcinogen hazard.

In general, this project will strive to efficiently decipher biological pathway and the mechanistic drivers of toxicity that will ultimately be used to build a suite of “systems toxicology” models. These models will be the basis for the development of expertise and tools for aiding mechanistic and predictive toxicology.