Moving towards predictive toxicology - a systems biology approach

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http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/19789 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/19789 http://eprints.org/relation/isIndexCodesVersionOf http://etheses.bham.ac.uk/id/document/19789 archive 2795 disk0/00/00/33/42 2012-05-25 08:58:17 2019-01-23 09:56:04 2012-05-25 08:58:17 thesis show 0 Antczak Philipp Falciani Francesco University of Birmingham Moving towards predictive toxicology - a systems biology approach unpub QH301 10col_life 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 effectiveness 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 pathway-level 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to improvements in risk assessment and environmental monitoring. 2012-07 2011-09 graduation eng author unchecked This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. public 223 University of Birmingham School of Biosciences d_ph na 2012-07 graduation