Universiteit Leiden

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Research project

Mathematical modeling of cellular stress pathways for mechanistic understanding of chemical-induced liver injury

Cellular stress response pathways are activated upon exposure to chemicals and help organisms deal with various molecular dangers (e.g. oxidative stress). When these pathways become hyper-activated an adverse response takes place and cells die, which may lead to organism-level toxicity such as drug-induced liver injury. To improve the prediction of such adversity, we established an imaging platform with which we can follow the chemical-induced temporal activation of various fluorescent reporters that represent different molecular components of cellular stress response pathways at the single cell level. Muriel will construct mathematical models to describe such dynamic data on DNA damage and inflammatory stress response activation and onset of adversity. Moreover, crosstalk between these pathways will be investigated in the models based on gene knockdown experiments.

2018  -   2022
Joost Beltman

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