Projects / Programmes
Resolving molecular mechanisms underlying reduced fish cell population growth upon chemical exposure
| Code |
Science |
Field |
Subfield |
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| Code |
Science |
Field |
| 2.08 |
Engineering and Technology |
Environmental biotechnology
|
ecotoxicology, chemical stress, fish cell lines, translation, growth
Data for the last 5 years (citations for the last 10 years) on
April 18, 2024;
A3 for period
2018-2022
Data for ARIS tenders (
04.04.2019 – Programme tender,
archive
)
| Database |
Linked records |
Citations |
Pure citations |
Average pure citations |
| WoS |
239 |
6,534 |
5,484 |
22.95 |
| Scopus |
269 |
7,651 |
6,421 |
23.87 |
Researchers (12)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0105 |
National Institute of Biology |
Ljubljana |
5055784 |
13,251 |
Abstract
Fish are a fascinating and important group of organisms that populates a huge variety of habitats, while providing manifold ecosystem service. At the same time, fish are sensitive to a variety of stressors, including chemical pollution. It is for these reasons that they play a key role in the environmental risk assessment of chemicals, with impact on survival and growth being measured in laboratory experiments as proxy for fish population health. Yet, such laboratory animal experiments are ethically problematic and very resource intensive. Recently, we have shown for a range of chemicals, that a one-week long in vitro assay based on the measurement of fish cell population growth is able to predict the retardation of growth in live fish seen after month long chemical exposure to the same chemicals, which makes it a very promising alternative to the animal experiment. However, these results on very different chemicals beg the question: how can chemicals with very different structures and presumably different mechanisms of biological action lead to the same overall outcome - reduced cell population, ergo reduced fish growth? Being able to answer this question would, for the first time, allow identifying different paths of reduced fish cell population growth, hence furthering knowledge in fish physiology and toxicology. It would moreover facilitate the transition from in vivo to in vitro testing based on transparent chemical structure-biological mechanism relationships along with detailed knowledge on the breadth and limits of the applicability of the in vitro assay. In this project, we will answer this question with a systems toxicology approach, using an innovative combination of experimental and computational methods: cell-based chemical exposure experiments, cell-based morphological and functional profiling, genome-wide transcriptomics and translatomics, analysis via bioinformatics and network-based approaches and finally confirmation of the in vitro results in an in vivo system. Multiplexed fluorescence assays, i.e. “cell painting”, and cellular composition measurements will provide us with chemical-specific cellular phenotypic profiles. The omics measurements will provide the chemical-specific molecular profiles. This will be followed by statistical analysis of the profiles, both separately and in combination, and thereby the definition of molecular and phenotypic biomarkers of reduced fish growth. The obtained dataset will also be integrated into a newly developed knowledge-based causal network, comprising known molecular pathways that control cellular proliferation and cell death, the two processed underlying changes in cell population growth. This integration will allow us to provide quantitative prediction of chemical effects and the molecular mechanisms behind them, based on the molecular data alone. Finally, the identified biomarkers will be tested in vivo in zebrafish to confirm that the mechanisms underlying reduced cell population growth in vitro are also active in the living animal. In this way, our project will not only provide insight into the molecular mechanisms underlying reduced fish growth, but also enhance the confidence into in vitro assays in general, as replacement for animal-based testing.
