Research Program

The research program of the Netherlands Toxicogenomics Centre is aimed at addressing current dilemmas in toxicology associated with the risk assessment of chemicals. There is a clear demand for new types of mechanism-based studies, not only to fill the current gaps of knowledge and to improve our understanding of the toxicological mode of action studies but also to develop efficient test protocols to bridge the gap between in vitro mechanism-based studies and in vivo empirical studies.

Further, new developments are needed to better understand in vitro models as such, since current methodologies are either too descriptive (e.g. cytotoxicity as endpoint) or too limited from a mechanistic point of view (e.g. gene expression of only a few genes).

NTC will propel mechanistic toxicogenomics research in order to discover selected sets of genes (bridging, mechanism-based, pathway supported effect markers) predominantly in in vitro systems, which are combined with a thorough understanding of molecular mechanisms of in vivo toxicity so that animal testing may eventually be replaced by evaluating these fingerprints in human target cells in vitro.
The Centre’s Research Plan is to develop, valorize and embed Applied Systems Toxicology for the purpose of the safety assessment of substances. These applied systems toxicology methods will be integrative across multiple dimensions, including:

  • Across technology platforms, including genomics, proteomics, metabonomics, bioinformatics, as well as more recently developed methodologies such as microRNAs and siRNA knockouts;
  • Across varied cellular, animal, and human biological systems;
  • Across major human biological systems through which most toxicity is observed, including carcinogenesis, organ-specific toxicity, immunotoxicity, and reprotoxicity.

NTC’s program will comprise the following research lines:

  • Chemical carcinogenesis
  • Organ-specific toxicity
  • Immunotoxicity
  • Reproduction toxicity
  • Toxicoinformatics

This multidimensional integrative approach is essential to realizing the promise of the emerging applied systems toxicology paradigm, to overcome the shortcomings of previous inadequately integrated approaches and to efficiently meet the growing demands of societal and governmental safety mandates. It is this considerable breadth of technology, systems, and pathways of toxicity that will enable NTC to identify and characterize the common nodes of toxicity that represent the core promise and value of the applied systems toxicology paradigm.
NTC’s research activities will thus produce:

  1. Knowledge of toxicological mechanisms-of-action and toxicogenomics methodologies as extracted from the database
  2. Toxicology tools (e.g. gene chips) developed on the basis of the analysis of database results

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