Moving Towards Predictive Toxicology - A Systems Biology Approach

Antczak, P ORCID: 0000-0001-9600-7757 (2012) Moving Towards Predictive Toxicology - A Systems Biology Approach. PhD thesis, Unspecified.

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Abstract

Human health and the environment are at risk of being exposed to a large number of hazardous chemicals each day. Unfortunately, many of these chemicals have no or little recorded toxicity information. Predictive toxicology aims to provide tools and methodologies to address this issue. In combination with systems biology approaches these can provide a powerful toolbox for understanding the impact of chemicals on biological species. The work presented within this thesis demonstrates the e ectiveness of such approaches in the context of industrial and environmentally relevant species. More specifically we focus on characterization of a general toxicity mechanism in Rattus norvegius and Daphnia magna as well as for the first time demonstrate that the transcriptional response of D. magna is predictive not only of chemical class but also of measured toxicity. We also show that inclusion of pathwaylevel information can increase biological interpretability in non-model species. Lastly, we provide evidence supporting the application of reverse engineering methodologies in the context of identifying adverse outcome pathways in Pimephales promelas, an environmentally relevant species. Ultimately, our results have shown that these approaches can provide highly relevant information in model and non-model species. Further development building on these results could potentially lead to improvements in risk assessment and environmental monitoring.

Item Type:	Thesis (PhD)
Depositing User:	Symplectic Admin
Date Deposited:	06 Apr 2016 10:40
Last Modified:	17 Dec 2022 02:27
DOI:	10.17638/03000035
Supervisors:	Falciani, F ORCID: 0000-0003-1432-2871
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3000035