Spin-off for chemical safety
Leiden University – towards a spin-off for chemical safety assessment
When chemicals injure cells, that injury initiates response pathways that signal stress in the cells. The strong activation of these pathways signals the onset of toxicity.
Using genetically-engineered biomarkers with fluorescent proteins, Leiden University has developed over 50 different cell lines that “report” such stress response pathways. Live cell confocal microscopy accurately quantifies activation of these stress pathways (upon chemical exposure) over time, while automated image acquisition and analysis allows efficient and cost- effective high throughput screening.
The goal is to provide detailed mechanistic information allowing temporal dynamics of stress proteins on a single cell or population level, which will result in a toxicity liability score to rank the chemicals based on maladaptive pathway activation and, ultimately, dose response modelling of treatment effects. This information will contribute to safe design for green chemistry and drug development.
The 50-plus reporter cell lines cover a wide range of stress pathways, e.g. oxidative stress, ER stress/unfolded protein stress, inflammation, DNA damage, heat shock stress, heavy metal stress, autophagy and hypoxia.
This platform is currently being incorporated in a spin-off company that will offer contract research. The imaging-based cell stress reporter platform is unique in that it allows:
- Improved prediction of target organ toxicity testing
- Temporal and quantitative analysis of cellular stress response activation
- Single cell as well as population dynamics analysis
- Applications for drug discovery to modulate cell stress response signaling