Future Toxicology: Better predicting Toxicant-induced cell fate.

Descripción del proyecto

Mejora de la predicción de la toxicidad química

La toxicología moderna avanza hacia enfoques computacionales donde la predicción de la toxicidad se basa en conjuntos de datos de estructuras químicas y resultados toxicológicos. Sin embargo, estos enfoques se ven limitados por nuestra falta de una comprensión completa sobre la manera en que las sustancias químicas afectan a las células. El proyecto financiado con fondos europeos TOXIFATE tiene por objeto desarrollar nuevos ensayos para detectar los cambios celulares inducidos por sustancias químicas. La investigación se centrará en la miotoxicidad, un tipo de toxicidad grave caracterizado por la degradación de los músculos esqueléticos. Los científicos generarán datos transcriptómicos para describir las respuestas de estrés y muerte celulares, y utilizará estos datos para desarrollar nuevos enfoques computacionales para predecir mejor la toxicidad.

Objetivo

TOXIFATE will help change the paradigm of chemical safety assessment and give the next generation of toxicologists the fundamental knowledge and experimental skills that are required to bring about this change. The safe use of chemicals is essential for global prosperity and human health and this is entirely dependent upon robust toxicology. For practical, scientific and ethical reasons, modern toxicology is moving to computational approaches in which large datasets describing chemical structures and toxicological outcomes are used to predict toxicity. The promise of this approach was recently demonstrated when computational approaches for the first-time outperformed animal testing in predicting human toxicity. Nonetheless, our ability to predict toxicity is poor because our understanding of how chemicals affect cells is still rudimentary. TOXIFATE will provide intersectoral training to 2 researchers who will build new assays to detect toxicant-induced changes in cells. Multi-disciplinary training will generate unique high-content and transcriptomic data describing cell stress and cell death responses. This multidimensional dataset will be used to develop novel computational approaches to improve toxicity prediction. TOXIFATE will focus on chemical-induced myotoxicity, a severe and sometimes life-threatening toxicity that is characterized by skeletal muscle breakdown. Although at least 200 drugs and chemicals cause myotoxicity, it is relatively under-investigated and what is learnt here to improve prediction of myotoxicity will also be used to improve prediction of other types of toxicity. TOXIFATE researchers will bridge the gap between state-of-the-art science and chemical hazard and risk assessment and be equipped for career paths in the emerging computational toxicology sectors. TOXIFATE will also aid the EU and the global community by quickly, ethically and economically addressing the societal challenge of better identifying chemical hazards to human health.