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Projects / Programmes source: ARIS

Resolving molecular mechanisms underlying reduced fish cell population growth upon chemical exposure

Research activity

Code Science Field Subfield
4.06.00  Biotechnical sciences  Biotechnology   

Code Science Field
2.08  Engineering and Technology  Environmental biotechnology  
Keywords
ecotoxicology, chemical stress, fish cell lines, translation, growth
Evaluation (rules)
source: COBISS
Points
4,212.21
A''
1,386.96
A'
2,849.66
A1/2
3,182.63
CI10
5,495
CImax
261
h10
39
A1
16.18
A3
5.93
Data for the last 5 years (citations for the last 10 years) on April 22, 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)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  19116  PhD Špela Baebler  Biotechnology  Researcher  2021 - 2024  313 
2.  54569  PhD Carissa Robyn Bleker  Biotechnology  Researcher  2021 - 2024  15 
3.  12688  PhD Kristina Gruden  Biotechnology  Researcher  2021 - 2024  985 
4.  51987  PhD Mojca Juteršek  Biotechnology  Junior researcher  2021 - 2022  42 
5.  37409  PhD Maja Križnik  Biotechnology  Researcher  2021 - 2024  42 
6.  29617  PhD Marko Petek  Biotechnology  Researcher  2021 - 2024  168 
7.  34502  PhD Živa Ramšak  Biology  Researcher  2021 - 2024  118 
8.  50566  PhD Špela Tomaž  Biotechnology  Researcher  2021 - 2024  28 
9.  36377  PhD Miha Tome  Biotechnology  Researcher  2022 - 2024  31 
10.  39320  PhD Maja Zagorščak  Interdisciplinary research  Researcher  2021 - 2024  57 
11.  32446  PhD Jan Zrimec  Biochemistry and molecular biology  Researcher  2022 - 2024  97 
12.  27522  PhD Anže Županič  Systems and cybernetics  Head  2021 - 2024  179 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0105  National Institute of Biology  Ljubljana  5055784  13,256 
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.
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