Evaluating Dictyostelium discoideum as a Model for the Evaluation of Teratogenic Compounds

Lead Research Organisation: University College London
Department Name: Genetics Evolution and Environment

Abstract

The evaluation of the safety of new compounds both for medical and environmental application is a tightly regulated process with worldwide legislation. Guidelines for developmental and reproductive toxicity (DART) testing are a critical aspect of new compound evaluation requiring strict in vivo testing. Current EU DART testing guidelines result in DART accounting for the majority of animals used and financial costs of new compound compliance testing. The improvement and critically the development of new alternative models is essential for the improvement in current DART testing processes.
Dictyostelium discoideum's unique developmental cycle has innate advantages over current alternative assays and has the potential to be developed as a new model for DART testing. However, previous attempts to characterize D. discoideum as a model have had limited scope. By developing new HTP D. discoideum toxicity screening assays we have been able to show that different toxicity endpoints across a broad range of compounds significantly correlates between D. discoideum and mammalian model systems. These results are together with the application of next generation functional genomic REMI-Seq screens highlighting the potential for the D. discoideum model to be developed into an alternative system for DART testing.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M50340X/2 02/10/2017 01/10/2019
1625324 Studentship BB/M50340X/2 01/10/2015 31/12/2019 Robert Baines