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REMI-seq analysis of D. discoideum cells treated with Lithium or Valproic acid

Citation

Thompson, Christopher (2021), REMI-seq analysis of D. discoideum cells treated with Lithium or Valproic acid, Dryad, Dataset, https://doi.org/10.5061/dryad.z612jm6cb

Abstract

A critical aspect of toxicity evaluation is developmental and reproductive toxicity (DART) testing. Traditionally, DART testing has been conducted in vivo in mammalian model systems. New legislation aimed at reducing animal use and the prohibitive costs associated with DART testing, together with a need to understand the genetic pathways underlying developmental toxicity means there is a growing demand for alternative model systems for toxicity evaluation. Here we explore the potential of the eukaryotic social amoeba Dictyostelium discoideum, which is already widely used as a simple model system for cell and developmental biology, as a potential non-animal model for DART testing. We developed assays for high-throughput screening of toxicity during D. discoideum growth and development. This allowed the toxicity of a broad range of test compounds to be characterized, which revealed that D. discoideum can broadly predict mammalian toxicity. In addition, we show that this system can be used to perform functional genomic screens to compare the molecular modes of action of different compounds. For example, genome wide screens for mutations that affect lithium and valproic acid toxicity allowed common and unique biological targets and molecular processes mediating their toxicity to be identified. These studies illustrate that D. discoideum could represent a predictive non-animal model for DART testing due to its amenability to high throughput approaches and molecular genetic tractability.

Usage Notes

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Funding

Wellcome Trust, Award: 095643/A/11/Z

Wellcome Trust, Award: 101582/Z/ 13/Z

Wellcome Trust, Award: 105610/Z/14/Z

Biotechnology and Biological Sciences Research Council