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Frontiers in toxicogenomics in the twenty-first century—the grand challenge: to understand how the genome and epigenome interact with the toxic environment at the single-cell, whole-organism, and multi-generational levels

Ruden, D.M., Gurdziel, K., Aschner, M.

In 2011, we wrote the inaugural Grand Challenge for Frontiers in Toxicogenomics, a specialty section of Frontiers in Genetics. In the original Grand Challenge, we argued that the fields of “Genomics” and “Toxicology” needed to be merged into the new field of “Toxicogenomics.” Toxicology in the twentieth century involved animal testing and LD50 (Lethal Dose 50) levels where half the population of animals die from the toxin after a certain amount of time, such as in one week or one month. Toxicogenomics in the twenty-first century, in contrast, utilizes modern genetics, epigenetics, and molecular biology technologies.

Toxicogenomics in the twenty-first century should involve more research that utilizes whole-genome sequencing of model-organism or human-stem-cell-derived “organoids,” single-cell analyses, proteomics, complex genetics with conditional-lethal, knock-in or knock-out transgenes, and bioinformatics technologies.

Ideas for research topics in Toxicogenomics include:

  • Organoid Toxicology Using Primary Cells and hESC-Derived Tissues.
  • Single-Cell Transcriptomic Analyses of Toxicant-Exposed Tissues.
  • Single-Cell Epigenomic Analyses of Toxicant-Exposed Tissues.
  • Proteomics Technologies of Toxicant-Exposed Tissues.
  • Multigenerational and Transgenerational Inheritance of Adaptive Epigenetic Changes of Toxicant-Exposed Model Animals and Humans.
  • The Role of Extracellular Vesicles in Transmitting Signals Throughout the Organism After Toxicant Exposure.
  • Imaging of Intracellular Alternations Caused by Toxicant Exposure.
  • Toxicant-Specific eQTLs (Expression Quantitative Trait Loci).
  • Exposures Measurements from Biobanked Tissues, Such as, Neonatal Dried Blood Spots and Shed Teeth.
  • Toxicant Effects on the Microbiome.
  • Sex-Specific Effects of Toxicants. 
  • Novel Methods—Second- and third-generation DNA sequencing technologies in Toxicogenomics, GWAS, etc.

Citation

Ruden, D.M., Gurdziel, K., Aschner, M. "Frontiers in toxicogenomics in the twenty-first century—the grand challenge: to understand how the genome and epigenome interact with the toxic environment at the single-cell, whole-organism, and multi-generational levels" Frontiers in Genetics (2017): 173